Phylogeny of Culex theileri virus flavivirus in Spain, Myanmar, Portugal and Turkey

Objective: To study the genetic diversity of Culex theileri flavivirus and the spread of this virus among Spain, Portugal and Turkey.Methods: A database consisting of 55 sequences of the NS5/3'UTR region of Culex theileri flavivirus group downloaded from GenBank were aligned and manual edited with Bioedit.ModelT est v.3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data.Maximum likelihood analysis was performed using MEGA7.The phylogenetic signal of the dataset was investigated by the likelihood mapping analysis.Results: The phylogenetic tree showed three clusters.Myanmar sequences clusterd together with Turkish sequences, Spain and Portugal strains grouped together and two Turkish sequences grouped separately.Selective pressure analysis showed a moderate percentage of sites(22.5%) under pervasive negative selection and only 1% under pervasive positive selection.The sites subject to selective pressure in CTFV RdRp NS5 fragments have been located onto the predicted three-dimensional structure.Conclusions: Phylogenetic and evolutionary analysis can be an important tool for understanding the evolutionary impact of the probable contemporary existence between nonpathogenic and pathogenic flaviviruses among these vectors.

Inter/intra investigator variation in orchidometric measurements of testicular volume by ten investigators from five institutions

瞄准：为了执行质量控制，为一个多中心在阴囊的体积大小上学习男繁殖功能的流行病学的学习。方法：我们由十个调查者与一项平衡任务构造了一个数据矩阵 2 连续的天(andrological 事业：4-21 年) 从五，机构和 12 个男志愿者变老 20-26 年。阴囊的体积被 Prader 的 orchidometer 测量。一个有技能的技术员也执行了阴囊的体积的超声估计。结果：一个统计上重要的内部调查者的变化两个都被作出对有利的裁决睾丸(P 【 0.05 ) 。另外，在阴囊的体积测量有一个统计上重要的 investigator-by-volunteer 相互作用(P 【 0.01 ) 。然而，有不，统计上，在二大小的有效差量为也表现在连续的天睾丸。为由 ultrasonography 估计了的权利和左睾丸的阴囊的体积是比用 orchidometer 的结果小的。然而，没有统计意义(P 】 0.05 ) 。根据调查者的经验的差别显著地没在任何一个睾丸与大小的精确性相关。结论：现在的学习在十个调查者之中在阴囊的体积的评价的结果揭示了有效差量，但是 intra 调查者变化不是可观的。训练改进并且测量的合适的标准化将在基于 andrological 考试开始多中心研究前是必要的。

Changes of liver fat content and transaminases in obese children after 12-mo nutritional intervention

AIM:To assess a relationship between longitudinal changes in liver fat content and biochemical parameters in obese children after 1-year nutritional intervention.METHODS:Forty-six obese children, 21 males and 25females, aged 6-14 years, underwent metabolic measurements, liver ultrasonography(US) and chemicalshift magnetic resonance imaging(MRI) examinations at baseline and after 1-year nutritional intervention. A child was defined obese if her/his body mass index(BMI)was above the age- and sex-adjusted BMI Cole's curve passing through the cut-off of 30 kg/m2 at 18 years.BMI Z scores were calculated and adjusted for age and gender by using the Cole's LMS-method and Italian reference data. Biochemistry included serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST). Abdominal US and chemical-shift MRI were performed according to a randomized sequence.The same radiologist performed US by a GE Logiq 9(General Electric Healthcare Medical Systems, Milwaukee, WI, United States) using a 3.5-MHz convex array transducer. Liver echogenicity was evaluated independently on videotape by 3 radiologists unaware of the child and MRI outcomes, and a consensus was established. Another experienced radiologist, unaware of the child and US data, performed the abdominal chemicalshift MRI with a 1-t system NT-Intera(Philips Medical Systems, Best, The Netherlands) and a phased-array coil. Liver fat fraction(FF) on MRI was judged elevated when greater than 9%. A FF>18% was considered expressing more severe cases of fatty liver according to Fishbein. A nutritional-behavioral intervention was recommended to promote a normocaloric balanced diet and active lifestyle based on the Italian guidelines for treatment of childhood obesity.RESULTS:Compared to baseline, at the end of intervention children showed lower intakes of energy(mean± SD:2549±1238 Kcal vs 1770±622 Kcal, P<0.0001), total fat(90±47 g vs 52± 23g, P<0.0001),carbohydrates(356±174g vs 241±111 g, P=0.001),and protein(99±48g vs 75±23g, P=0.006) intakes. Prevalence of FF≥9% declined from 34.8%to 8.7%(P<0.01), with a mean reduction of 7.8%(95%CI:5.0-10.6). At baseline, FF was associated with liver biochemical parameters(maximum P<0.001). At the end of the intervention association was found with AST(P=0.017). Change of FF was associated with change in AST(P =0.027) and ALT(P=0.024). Rate of increased liver echogenicity declined from 45.6% to21.7%(P<0.0001). Liver echogenicity was associated with ALT at baseline only(P<0.001). An age-and sexadjusted multiple regression analysis showed that FF change was independently associated with change in serum AST(adjusted regression coefficient 0.348, P=0.048).CONCLUSION:The results suggest that in obese children longitudinal changes in liver fat content based on MRI may be associated with change in serum transaminases suggesting novelty in monitoring nonalcoholic fatty liver disease.

Validations of new cut-offs for surgical drains management and use of computerized tomography scan after pancreatoduodenectomy:The DALCUT trial

BACKGROUND Postoperative pancreatic fistula(POPF)is the most fearful complication after pancreatic surgery and can lead to severe postoperative complications such as surgical site infections,sepsis and bleeding.A previous study which identified cut-offs of drains amylase levels(DALs)determined on postoperative day(POD)1 and POD3,was able to significantly predict POPF,abdominal collections and biliary fistulas,when related to specific findings detected at the abdominal computerized tomography(CT)scan routinely performed on POD3.AIM To validate the cut-offs of DALs in POD1 and POD3,established during the previous study,to assess the risk of clinically relevant POPF and confirm the usefulness of abdominal CT scan on POD3 in patients at increased risk of abdominal collection.METHODS The DALCUT trial is an interventional prospective study.All patients who will undergo pancreatoduodenectomy(PD)for periampullary neoplasms will be considered eligible.All patients will receive clinical staging and,if eligible for surgery,will undergo routine preoperative evaluation.After the PD,daily DALs will be evaluated from POD1.Drains removal and possible requirement of abdominal CT scans in POD3 will be managed on the basis of the outcome of DALs in the first three postoperative days.RESULTS This prospective study could validate the role of DALs in the management of surgical drains and in assessing the risk or relevant complications after PD.Drains could be removed in POD3 in case of POD1 DALs<666 U/L and POD3 DALs<207 U/L.In case of POD3 DALs≥252,abdominal CT scan will be performed in POD3 to identify abdominal collections≥5 cm.In this latter category of patients,drains could be maintained beyond POD3.CONCLUSION The results of this trial will contribute to a better knowledge of POPF and management of surgical drains.

Estimation of the Piecewise Exponential Model by Bayesian P-Splines via Gibbs Sampling: Robustness and Reliability of Posterior Estimates

In the investigation of disease dynamics, the effect of covariates on the hazard function is a major topic. Some recent smoothed estimation methods have been proposed, both frequentist and Bayesian, based on the relationship between penalized splines and mixed models theory. These approaches are also motivated by the possibility of using automatic procedures for determining the optimal amount of smoothing. However, estimation algorithms involve an analytically intractable hazard function, and thus require ad-hoc software routines. We propose a more user-friendly alternative, consisting in regularized estimation of piecewise exponential models by Bayesian P-splines. A further facilitation is that widespread Bayesian software, such as WinBUGS, can be used. The aim is assessing the robustness of this approach with respect to different prior functions and penalties. A large dataset from breast cancer patients, where results from validated clinical studies are available, is used as a benchmark to evaluate the reliability of the estimates. A second dataset from a small case series of sarcoma patients is used for evaluating the performances of the PE model as a tool for exploratory analysis. Concerning breast cancer data, the estimates are robust with respect to priors and penalties, and consistent with clinical knowledge. Concerning soft tissue sarcoma data, the estimates of the hazard function are sensitive with respect to the prior for the smoothing parameter, whereas the estimates of regression coefficients are robust. In conclusion, Gibbs sampling results an efficient computational strategy. The issue of the sensitivity with respect to the priors concerns only the estimates of the hazard function, and seems more likely to occur when non-large case series are investigated, calling for tailored solutions.

Adjuvant chemotherapy for gastric cancer:Current evidence and future challenges

Gastric cancer still represents one of the major causes of cancer mortality worldwide.Patients survival is mainly related to stage,with a high proportion of patients with metastatic disease at presentation.Thus,the cure rate largely depend upon surgical resection.Despite the additional,albeit small,benefit of adjuvant chemotherapy has been clearly demonstrated,no general consensus has been reached on the best treatment option.Moreover,the narrow therapeutic index of adjuvant chemotherapy(i.e.,limited survival benefit with considerable toxicity)requires a careful assessment of expected risks and benefits for individual patients.Treatment choices vary widely based on the different geographic areas,with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States.In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses.The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery;the same Authors also showed that disease free survival may be used as a surrogate end-point for overall survival.We finally discuss future research issues such as the need of economic evaluations,development of prognostic or predictive biomarkers,and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.

十位来自五个不同机构的调查者进行睾丸体积测量的组间和组内差异

目的:对多单位男性生殖功能流行病学研究中的睾丸体积测量进行质量控制研究。方法:我们构建了一个平衡分配数据矩阵,由10位来自5个不同研究所的调查者(从事男科学工作4到21年)在连续的两天内用 Prader 睾丸测量器测量12个男性志愿者(20—26岁)的睾丸体积。睾丸体积超声估计由一个经验丰富的技术人员完成。结果:10个调查者测量双侧睾丸体积的结果存在显著的组间统计差异(P<0.05)。睾丸体积测量结果显示调查者和志愿者之间存在显著的统计意义上的相互作用(P<0.01)。但是连续两天通过2种测量方法测得的双侧睾丸体积结果之间无显著差异。用超声波检查法测得的左右睾丸体积小于用睾丸测量器测得的值,但无显著差异(P>0.05)。调查者的工作经验没有显著影响睾丸体积测量结果的精确度。结论:研究表明10个调查者对睾丸体积的估计结果之间有显著差异,但组内差异不明显。因此,有必要在多单位男科学调研之前进行良好的培训和确定适当的测量标准。

Microscopic tumor foci in axillary lymph nodes may reveal the recurrence dynamics of breast cancer

Dear Editor,In early breast cancer,the prognostic value of the num-ber of macroscopically metastasized axillary nodes has been recognized in earlier reports[1].However,the impact of microscopic tumour cell deposits on the sur-vival outcome of early breast cancer patients is still debated[2].This issue has gained increasing attention since the implementation of sentinel node biopsy in axil-lary node staging for tailoring breast cancer treatments,and the status of the single resected node would deter-mine the clinical decision of whether or not to perform the axillary lymph node dissection[3].Moreover,this issue raises more questions on whether to administer primary or adjuvant systemic treatment for patients with lymph nodes bearing isolated tumour cells(pN0[i+])or micrometastases(pN1mi).Despite the wide debate on the clinical treatment dilemma encountered by early breast cancer patients with microscopic tumour cell deposits,the biology underlying different pathologi-cal presentations at microscopic level(pN0,pN0[i+],pN1mi)and the disease outcomes remain poorly known.In an attempt to shed some light on this topic,we have analyzed,in the context of dormancy-based metastasis development model[4],early breast cancer patients con-ventionally classified as pN0(tumour foci with largest diameter≤2 mm)[5]by systematically reassessing their tumor recurrence dynamics following primary tumour resection at a single institution.