Antimicrobial susceptibility of strains of Enterobacteriaceae isolated from bloodstream infections using current CLSI and EUCAST breakpoints

Understanding local susceptibility patterns is important when selecting antimicrobials for initial empirical antibiotic-therapy of bloodstream infections. Because the determination of susceptibility is dependent on the breakpoints used, the aim of the study was to compare the antimicrobial susceptibility results to different classes of antibiotics of 512 strains of Enterobacteriaceae (200 ESβL positive) isolated from bloodstream using CLSI 2013 and current EUCAST 2013 guidelines to evaluate the impact of break-point discrepancies. The results of the study showed that statistically significant discrepancies (p ≤ 0.001) were found for amoxicillin/clavulanic acid, piperacillin alone or with tazobac-tam, imipenem, meropenem, cefepime (only ESβL negative isolates), amikacin and gentamicin using current CLSI or EUCAST interpretive criteria. Further harmonization of CLSI and EUCAST breakpoints is warranted. This study could give useful information to physicians for managing bloodstream infections caused by Enterobacteriaceae.

大气污染物致突变研究中的Breakpoint回归

本文在用Ames试验和SOS显色法两个细菌短期测试系统研究广州地区1991年的大气总悬浮颗粒（TSP）二氯化烷（DCM）提取物遗传毒性的基础上，建立了气温（T），气压（P），风速（W），降雨量（R），相对湿度（RH）5种主要气象因素与诱变力和诱导力之间的Breakpoint回归模型，回归效果显著。

基于CAPM模型的金融海啸对沪市结构冲击研究

全球金融海啸是百年一遇的金融危机。本文在CAPM理论视界下引入哑元变量构筑计量模型并利用Chow Breakpoint Test对从上证A股选取的样本进行关于金融海啸对沪市A股市场结构性冲击的实证分析与比较后发现：金融海啸对A股市场没有带来突变性的结构冲击,并基于中国金融市场现实状况对这一结论作出了若干解释。

Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs:A literature review

Chronic myeloid leukemia(CML)is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly―the presence of the Philadelphia chromosome.The advances in cytogenetic and molecular assays are of great importance to the diagnosis,prognosis,treatment,and monitoring of CML.The discovery of the breakpoint cluster region(BCR)-Abelson murine leukemia(ABL)1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein.Tyrosine kinase inhibitors(known as TKIs)are the standard therapy for CML and greatly increase the survival rates,despite adverse effects and the odds of residual disease after discontinuation of treatment.As therapeutic alternatives,the subsequent TKIs lead to faster and deeper molecular remissions;however,with the emergence of resistance to these drugs,immunotherapy appears as an alternative,which may have a cure potential in these patients.Against this background,this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.

Tyrosine kinase inhibitors:Multi-targeted or single-targeted?

Since in most tumors multiple signaling pathways are involved,many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases.The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL,SCR,platelet derived growth factor,vascular endothelial growth factor receptor and epidermal growth factor receptor families.Both multi-kinase inhibitors and singlekinase inhibitors have advantages and disadvantages,which are related to potential resistance mechanisms,pharmacokinetics,selectivity and tumor environment.In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist.Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor.Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity,while differences in gene expression exist between tumor and stromal cells.Considering these aspects,one type of inhibitor can generally not be preferred above the other,but will depend on the specific genetic constitution of the patient and the tumor,allowing personalized therapy.The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered(epi)genetics of the tumor.This strategy might result in treatment by a single multi kinase inhibitor for one patient,but in treatment by a couple of single kinase inhibitors for other patients.

Layering-based Breakpoint Handling in Contour Line Extraction

This paper deals withthe automatic connection of contourlines extracted from a scanned browngeographical map. For the variety oftopographical elements contained on amap, the factors causing the interrup-tion of contour line are also multiform,which make the connection task verydifficult. On the basis of separatingthose elements always making the con-tours break and regarding them as ref-erent layers, a layering-based methodis presented. The purpose is to takeinto account property information (likeinclination and configuration) of con-tour lines when they come across otherdifferent symbols, such as gully, cliff,dry land and elevation annotation etc.In this paper, the authors propose thatit should be far more effective and di-rect to adopt different algorithmic op-erators to different factors than usingsingle one operator to all.

Ewing sarcoma of the jejunum: A case report and literature review

BACKGROUND Ewing sarcomas(ESs)are highly aggressive malignancy and are predominant in the long bones of extremities of children and young adults with a slight male predilection and rarely presents at extra skeletal locations.CASE SUMMARY A 55-year-old woman came to our hospital after finding elevated tumor biomarkers during her physical examination.Her enhanced computed tomography scan showed a jejunal mass.The patient underwent laparoscopic enterectomy.The mass was later diagnosed as ES,evidenced by fluorescence in situ hybridization whereby the GLP ES breakpoint region 1 probe was used,showing that more than 10%of the cells showed a red-green-yellow signal proving the breakpoint rearrangement of the ES breakpoint region 1 gene in chromosome 22.CONCLUSION We describe a case of localized ES at the jejunum in China based on the literature.

A new optimal approach to segmentation of 2D range scans to line sections

In order to obtain a compact and exact representation of 2D range scans,UKF(unscented Kalman filter) and CDKF(central difference Kalman filter) were proposed for extracting the breakpoint of the laser data. Line extraction was performed in every continuous breakpoint region by detecting the optimal angle and the optimal distance in polar coordinates,and every breakpoint area was constructed with two points. As a proof to the method,an experiment was performed by a mobile robot equipped with one SICK laser rangefinder,and the results of UKF/CDKF in breakpoint detection and line extraction were compared with those of the EKF(extended Kalman filter) . The results show that the exact geometry of the raw laser data of the environments can be obtained by segmented raw measurements(combining the proposed breakpoint detection approach with the line extraction method) ,and method UKF is the best one compared with CDKF and EKF.

On-Line Structural Breaks Estimation for Non-stationary Time Series Models

Non-stationary time series could be divided into piecewise stationary stochastic signal. However, the number and locations of breakpoints, as well as the approximation function of the respective segment signal are unknown. To solve this problem, a novel on-line structural breaks estimation algorithm based on piecewise autoregressive processes is proposed. In order to find the "best" combination of the number, lengths, and orders of the piecewise autoregressive (AR) processes, the Akaikes Information Criterion (AIC) and Yule-Walker equations are applied to estimate an AR model fit to the data. Numerical results demonstrate that the proposed estimation algorithm is suitable for different data series. Furthermore, the algorithm is used in a clinical study of electroencephalogram (EEG) with satisfactory results, and the ability to deal with real-time data is the most outstanding characteristic of on-line structural breaks estimation algorithm proposed.

Laboratory Experiments for Arsenic and Ammonium Removal The Combination of Breakpoint Chlorination and Iron（Ⅲ）-Coagulation

Currently, 15% of the total Hungarian population is affected by either the elevated arsenic or ammonium concentration of drinking water, and 8% is affected by both compounds. The break-point chlorination is a well-known method for ammonium removal, however, during the ammonium-removal process carcinogenic and mutagenic by-products （e.g., THM （trihalogenmethane） and AOX （absorbable organically bound halogens）） may be formed. In order to remove these harmful organic by-products, activated carbon adsorption has to be applied in the technology. The break-point chlorine dose is capable of oxidizing the As3＋ to As5＋. The oxidized form of arsenic can be easily converted to solid phase by adding coagulant （Fe（Ⅲ） or AI（Ⅲ） salt） to the water, and the formed iron/aluminium flocs can be removed by simple rapid sand filtration. Laboratory experiments were performed with raw water from two Hungarian settlements, where the water originated from a deep confined aquifer. In the studied settlements, six wells were in operation, and the supplied drinking water contained ammonium above the maximum allowable concentration, and the arsenic content was around the 10 μg/L standard value. It was found that higher chlorine dose （- 10 Cl2：NH4-N） was needed to achieve the breakpoint than the theoretical value （7.6）. The amount of by-products was also measured during the experiments. The AOX concentrations were significantly higher （21.6 μg/L to 143μg/L） in all cases than the THM concentrations （9-18 μg/L）. The needed coagulant doses were also studied in order to achieve the required arsenic concentrations. Fe（Ⅲ） coagulant was applied in all cases, and it was found that 1-1.5 mg/L Fe（Ⅲ） dose was sufficient to achieve 2-5 μg/L arsenic concentration in the treated water. Based on the results, it can be stated that the breakpoint chlorination combined with Fe（Ⅲ） coagulation is a potential technology to achieve the required ammonium and arsenic concentration at the studied settlements. However, activated carbon has to be installed in order to remove the harmful AOX compounds.

DETECTION OF BCL-2 GENE MAJOR BREAKPOINT REGION REARRANGEMENT IN HUMAN B-CELL LYMPHOMAS

Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of B-cell lymphomas were studied uslng DNA extracted from rresh-frozen tissues. The DNA samples were amplified by PCR for bcl-2 MBR/JH. The products of bcl-2/JH rearrangement were hybridized with an internal olignucleotide probe or bcl-2 MBR. Results The rearranged bcl-2MBR/JH gene was detected in 13 of the 25(52. o% ) follicular center lymphomas, according to REAL classification: 8 of 11 (72. 7%) grade 1, 2 of 5(40. 0%) grade I, and 3 of 90 (33. 3%) grade, 17 of 82(2o. 8%) cases or difruse large B-cell lymphomas were found to have detectable bel-2 MBR/J. rearrangement- Conclusion The rrequency or bcl-2 MBR/JH rearrangement in diffuse large B-cell lymphomas is significantly lower than those in follicular center lympkomas(X2= 9. 28, P <o. oo5), suggesting that bcl2/JH rearrangements occur mainly in follicular center lymphomas. in addition, the result of reconstruction experiments suggest that amplification or bcl-2 MBR/JH rearrangements by PCR is both sensitive and specific for detection of t (14; 18 ) translocation.

Compassionate Use of Midostaurin in Myeloid and Lymphoid Neoplasia with FGFR1 Abnormality

Background: Patients with stem cell myeloproliferative disorders have a particularly poor prognosis and limited treatment options, i.e. mainly aggressive chemotherapy or allogeneic stem cell transplantation. In 2004, Chen et al. reported a patient presenting a t(8;13) (p11;q12) cytogenic anomaly who responded positively to treatment with PKC412 (midostaurin), an oral multi-targeted tyrosine kinase inhibitor. Here, we report a second case treated with the above-mentioned drug. Patient: A 71-year-old woman was diagnosed as having chronic myelogenous leukaemia with eosinophilia secondary to t(8;13) with FGFR1 involvement. Due to her age, an allogeneic stem cell transplantation was not possible. Treatment: A treatment combining aggressive chemotherapy and midostaurin was explored. The patient received one cycle of hyper-CVAD chemotherapy followed by maintenance therapy with midostaurin. A relapse occurred after six months, and she was treated with four more cycles of hyper-CVAD chemotherapy. The patient entered a complete clinical, haematological and cytogenetic remission. A maintenance therapy with midostaurin continued for four months until she developed a chemoresistant relapse followed by acute leukaemia. Conclusion: This is the second case of a t(8;13) myeloid and lymphoid neoplasm with FGFR1 abnormalities treated successfully with midostaurin. Midostaurin is administered orally, allows for outpatient care and in this case showed only occasional and minimal side effects. The combination of hyper-CVAD and midostaurin extended survival by 21 months without allogeneic transplantation. This case further supports the possibility of using midostaurin for the treatment of other diseases with FGFR1 dysregulations;however, specific clinical trials are needed to confirm this hypothesis.

浅谈断 点管理

汽车市场在不断扩张,从而导致人们生活和工作节奏也在加快,汽车行业的竞争也在不断加剧。由于我国汽车行业的不成熟和竞争的剧烈,从而使得汽车的更新换代周期缩短,相应的产品缺陷在增加。因此,在产品上市以后,工厂内部和销售会不断反映产品缺陷。鉴于此,各主机厂或多或少都会存在零部件优化和变更,从而断点管理运营而生。

药敏试验方法的局限性及改进的建议

以CLSI提出的两种细菌药敏试验方法(纸片扩散法和肉汤稀释法)和对"breakpoint"标准的拟定为例,基于菌群生长动力学和临床对抗菌药物选择的需要,分析现行药敏试验存在的问题,并就病原菌的生态学、breakpoint制定、药敏试验方法的规范和抗药性网络建设等方面提出建议。

Time-series variation and attribution analysis of downward shortwave radiation over the Yunnan-Kweichow plateau from 1984 to 2018

The downward shortwave radiation(DSR)is a key input parameter for land surface models and climate models.Based on the daily averaged Global Land Surface Satellite downward shortwave radiation(GLASS-DSR)dataset over the Yunnan-Kweichow Plateau(YKP)from 1984 to 2018,this paper analyzes variation trend and breakpoints of DSR.The results show that:annual averaged DSR decreases at a decreasing rate of-1.84 W·m^(-2)·decade^(-1) over the YKP from 1984 to 2018;the overall distribution of interannual averaged DSR shows higher in the mid-west,and gradually decreasing from west to northeast over the YKP;the estimated averaged DSR is larger in spring than in summer due to the influence of the monsoon;monthly averaged DSR reaches its maximum in May and its minimum in December;breakpoints are found in the seasonal and trend components of daily averaged DSR.Eleven driving factors are examined for their effects on DSR variation,including annual average temperature,precipitation,10 m wind speed,aerosol optical thickness(AOT),total cloud cover,elevation,slope,aspect,longitude,latitude,and climate zones.According to thefindings,AOT predominates in the spatio-temporal distribution of DSR over the YKP.This study will contribute to studies related to climate change and highland radiation.

Antimicrobial susceptibility testing in veterinary medicine:performance,interpretation of results,best practices and pitfalls

The performance of antimicrobial susceptibility testing(AST)of bacteria and the interpretation of AST results for bacteria isolated from animals are complex tasks which must be performed using standard published methodology and overseen by experts in clinical microbiology and in consultation with clinical pharmacologists.Otherwise,AST has significant potential for errors and mistakes.In this review,we provide guidance on how to correctly perform AST of bacteria isolated from animals and interpret the AST results.Particular emphasis is placed on the various approved or published methodologies for the different bacteria as well as the application of interpretive criteria,including clinical breakpoints and epidemiological cut-off values(ECVs/ECOFFs).Application of approved interpretive criteria and definitions of susceptible,susceptible dose-dependent,nonsusceptible,intermediate,and resistant for clinical breakpoints as well as wild-type and non-wildtype for ECVs,are explained and the difficulties resulting from the lack of approved clinical breakpoints for other bacteria,indications,and animal species is discussed.The requirement of quality controls in any AST approach is also emphasized.In addition,important parameters,often used in monitoring and surveillance studies,such as MIC50,MIC90,and testing range,are explained and criteria for the classification of bacteria as multidrug-resistant,extensively drug-resistant or pandrug-resistant are provided.Common mistakes are presented and the means to avoid them are described.To provide the most accurate AST,one must strictly adhere to approved standards or validated methodologies,like those of the Clinical and Laboratory Standards Institute or other internationally accepted AST documents and the detailed information provided therein.

GAEP:a comprehensive genome assembly evaluating pipeline

With the rapid development of sequencing technologies,especially the maturity of third-generation sequencing technologies,there has been a significant increase in the number and quality of published genome assemblies.The emergence of these high-quality genomes has raised higher requirements for genome evaluation.Although numerous computational methods have been developed to evaluate assembly quality from various perspectives,the selective use of these evaluation methods can be arbitrary and inconvenient for fairly comparing the assembly quality.To address this issue,we have developed the Genome Assembly Evaluating Pipeline(GAEP),which provides a comprehensive assessment pipeline for evaluating genome quality from multiple perspectives,including continuity,completeness,and correctness.Additionally,GAEP includes new functions for detecting misassemblies and evaluating the assembly redundancy,which performs well in our testing.GAEP is publicly available at https://github.com/zyoptimistic/GAEP under the GPL3.0 License.With GAEP,users can quickly obtain accurate and reliable evaluation results,facilitating the comparison and selection of high-quality genome assemblies.

The small-island effect in amphibian assemblages on subtropical land-bridge islands of an inundated lake

The small-island effect （SIE） has become more and more part of the theoretical framework of island biogeography and biodiversity research. However, previous methods for the detection of SlEs are often flawed in one way or another, including not accounting for model complexity, not comparing all relevant models, and not including islands with no species. Therefore, the existence and the prevalence of the SIE may be dubious. In this study, after controlling for all these methodological shortcomings, we tested for the existence of the SlE in amphibian assemblages on subtropical landbridge islands created by the inundation of the Thousand Island Lake, China. We used the line transect method to determine the distribution of amphibian assemblages on 23 study islands during 3 breeding seasons from 2009 to 2011. To evaluate whether an SIE exists in amphibian assemblages, we compared the fit of a simple linearized power model with two most widely used breakpoint regression models. The information-theoretic multimodel inference approach based on Akaike＇s information criterion identified the left-horizontal SIE model as the best single model. Thus, we found strong evidence for the existence of an SIE in our system. The upper limit of the SlE for amphibian assemblages was 39.95 ha. Below this threshold area, amphibian richness varied independently of island size. The SlE in amphibian assemblages may be due to episodic disturbances, stochastic events, and nutrient subsidies from the lake. Our results indicate that all the islands 〉39.95 ha should be protected for the effective conservation of amphibian assemblages in our system.

Adaptive relay co-ordination using a busbar splitting approach for a system integrity protection scheme

Power system faults can often result in excessively high currents.If sustained for a long time,such high currents can damage system equipment.Thus,it is desirable to operate the relays in the minimum possible time.In this paper,a busbar splitting approach is used for adaptive relay setting and co-ordination purposes for a system integrity protec-tion scheme(SIPS).Whenever a fault occurs,the busbar splitting scheme splits a bus to convert a loop into a radial structure.The splitting schemes are chosen such that the net fault current is also reduced.Busbar splitting elimi-nates the dependency upon minimum breakpoints set(MBPS)and reduces the relay operating time,thus making it adaptive.The proposed methodology is incorporated into the IEEE 14-bus and IEEE 30-bus systems with single and multiple fault conditions.The modeling and simulation carried out in ETAP,and the results of the proposed busbar splitting-based relay co-ordination are compared with the MBPS splitting-based relay co-ordination.

The malaria transmission in Anhui province China

Plasmodium vivax and Plasmodium falciparum cases have opposite trends in Anhui China in the past decade.Long term and seasonal trends in the transmission rate of P.falciparum in Africa has been well studied,however that of P.vivax transmitted by Anopheles sinensis in China has not been investigated.There is a lot of work on the relationship between P.vivax cases and climatic factors in China,with sometimes contradicting results.However,how climatic factors affect transmission rate of P.vivax in China is unknown.We used Anhui province as an example to analyze the recent transmission dynamics where two types of malaria have been reported with differing etiologies.We examined breakpoints of the P.vivax and P.falciparum malaria long term dynamics in the recent decade.For locally transmitted P.vivax malaria,we analyzed the transmission rate and its seasonality using the combined human and mosquitos SIR-SI model with time-varied mosquito biting rate.We identified the effects of meteorological factors on the seasonality in transmission rate using a GAM model.For the imported P.falciparum ma-laria,we analyzed the potential reason for the observed increase in cases.The breakpoints of P.vivax and P.falciparum dynamics happened in a same year,2010.The seasonality in the transmission rate of P.vivax malaria was high(42.4%)and was linearly associated with temperature and nonlinearly with rainfall.The abrupt increase in im-ported P.falciparum cases after the breakpoint was significantly related to the increased annual Chinese investment in Africa.Under the conditions of the existing vectors of malaria,long-term trends in climatic fac-tors,and increasing trend in migration to/from endemic areas and imported malaria cases,we should be cautious of the possibility of the reestablishment of malaria in regions where it has been eliminated or the establishment of other vector-borne diseases.