Role of endogenous endothelin in endothelial dysfunction in murine model of systemic sclerosis: tight skin mice 1

Systemic sclerosis (SSc) is a systemic inflammatory disorder, resulting in severe vascular dysfunction. The endothelin (ET) system has vasoconstrictor and profibrotic properties and has been shown to be activated in SSc. ET antagonists are currently used in SSc‐related pulmonary arterial hypertension, but the endothelial impact of ET antagonists remains less known in SSc. We thus assessed the effects of the dual ET_A–ET_B antagonist, bosentan, on endothelial dysfunction in a murine model of SSc, the heterozygous tight‐skin mice 1 (TSK1⁺). Six‐week‐old TSK1⁺ were either untreated or treated for 6 weeks with bosentan (100 mg/kg/day), and compared with controls. Endothelial function was evaluated in isolated mesenteric resistance arteries, using a small vessel myograph. TSK1⁺ displayed endothelial dysfunction, as shown by a decreased response of mesenteric arteries to acetylcholine, especially in the presence of l ‐nitro‐arginine methyl ester (l ‐NAME), corresponding to NO‐independent, prostaglandin‐mediated relaxation. The NO‐independent relaxation was partially restored in bosentan‐treated TSK1⁺, and this was abolished by a cyclo‐oxygenase inhibitor. Therefore, the murine model of SSc, TSK1⁺ exhibits severe endothelial dysfunction of peripheral resistance arteries. The ET antagonist bosentan prevents endothelial alterations, suggesting a major role of ET in the adverse vascular effects of SSc.     

Latent heat flux estimation using trapezoidal relationship between MODIS land surface temperature and fraction of vegetation – application and validation in a humid tropical region

The present study was taken up with the objective of developing a methodology for estimation of actual evapotranspiration (AET) using only satellite data. Accordingly, an algorithm based on the popular Priestley–Taylor method was developed. While previous studies have assumed a triangular relationship between land surface temperature (LST) and fraction of vegetation (FV) to calculate the Priestley–Taylor parameter (φ), a trapezoidal relationship was adopted in the present study to enable applications in forested regions in the humid tropics. The developed algorithm was applied to the humid tropical Mae Klong region, Thailand, and latent heat flux (λ_ET) estimates were validated with measurements made at a flux tower located at the centre of the region. Moderate Resolution Imaging Spectroradiometer (MODIS) remote sensing satellite data products corresponding to the study area were used to derive various inputs required by the algorithm. Comparison of estimated and measured fluxes on five cloud-free days in 2003 yielded root mean square error (RMSE) of 64.73 W m^?2 which reduced to 18.65 W m^?2 when one day was treated as an outlier. The methodology developed in this study derived inputs only from satellite imagery and provided reasonably accurate estimates of latent heat flux at a humid tropical location.     

动态对比增强MRI衍生的药代动力学参数鉴别诊断原发性中枢神经系统淋巴瘤与胶质母细胞瘤

目的 探讨原发性中枢神经系统淋巴瘤（PCNSL）与胶质母细胞瘤（GBM）动态对比增强MRI衍生的药代动力学参数差异。方法 收集17例PCNSL与21例GBM,均接受常规及动态对比增强MR检查,测量双室Tofts模型下药代动力学参数容量转移常数（K^trans）、回流速率常数（K_ep）、血管外细胞外间隙容积分数（V_e）,及初始（60 s）对比剂浓度-时间曲线下面积（iAUC）。采用单因素方差分析比较PCNSL与GBM各自的强化瘤灶（ET）、瘤旁脑组织（PT）、正常侧脑组织（NP）间各参数差异;采用独立样本t检验比较二者间ET、PT、NP各参数的差异。结果 PCNSL与GBM间ET的K^trans、K_ep差异均有统计学意义（P均<0.05）,PT的K_ep差异有统计学意义（P<0.05）。PCNSL、GBM的ET与PT间K^trans、K_ep、V_e、iAUC差异均有统计学意义（P均<0.05）;PCNSL的PT与NP间K^trans差异有统计学意义（P<0.05）;GBM的PT与NP间K^trans及K_ep差异均有统计学意义（P均<0.05）。结论 动态对比增强MRI基于Tofts双室模型的药代动力学分析对PCNSL与GBM具有鉴别诊断价值。     

Assessing the impact of land cover map resolution and geolocation accuracy on evapotranspiration simulations by a land surface model

The land surface models used in numerical weather forecasts and hydrological applications rely on the accuracy of land cover maps available from satellite remote sensing to simulate the energy and water balance at the surface of the Earth. While the impact of classification accuracy on land surface simulations has already been reported, little attention has been paid on the consequences of land cover map uncertainty driven by geolocation accuracy. This impact on the estimated evapotranspiration (ET) from the land surface model H-TESSEL at spatial resolutions ranging from 1 to 30 km is evaluated here, making use of land cover maps at two different initial spatial resolutions, 300 and 1200 m, derived from the GlobCover global product. Geolocation uncertainty affects the land cover maps aggregated at different resolution (from 1.2 to 30 km). However, the effect decreases towards the coarsest resolutions. In addition, aggregated land cover maps are less affected by geolocation errors when the finest original resolution (300 m) is used. The maximum possible effect on ET is quantified over a heterogeneous/transition area in Europe. The result shows an impact up to 10% at 1.2-km resolution to less than 1% at 10-km resolution, at daily timescale, stressing the importance of such issues for kilometre scale applications of land surface models. The use of the highest initial land cover resolution (300 m) reduces by a factor 3 the impact of geolocation on estimated ET at 1.2- to 3-km scale. This study, therefore, stresses on the importance of a careful choice of the land cover map before carrying on land surface model simulations at the kilometre scale.     

T1～2期胃神经内分泌肿瘤转移的影响因素以及患者内镜和手术治疗后生存差异分析

目的 探讨T_1～2期胃神经内分泌肿瘤(G-NETs)患者的转移率及其相关危险因素，比较其内镜治疗(ET和手术治疗后长期生存结果。方法 分析SEER数据库数据，纳入2004年1月1日至2015年12月31日病理学诊断为G-NETs的患者1 258例。采用logistic回归分析G-NETs患者肿瘤转移的影响因素。在T_1～2N0M0期G-NETs患者中，采用倾向性评分匹配分析，比较匹配后接受ET与手术治疗患者的一般临床特征，采用Kaplan-Meier生存曲线和Cox比例风险模型分析两组患者总生存期(OS)差异和影响OS的危险因素。结果 1 258例G-NETs患者中，851例随访5年，有183例(21.5%)发生了淋巴结或远处转移，其中T1期(n=78)、T2期(n=105)患者的转移率分别为14.6%和33.3%(P<0.05)。多因素logistic回归分析发现，肿瘤组织分级G3/4、浸润固有肌层及肿瘤最大径>20 mm与T_1～2期G-NETs患者发生转移相关(P<0.05)。非转移组(n=668)患...     

Dissecting the functional significance of endothelin A receptors in peripheral nociceptors in vivo via conditional gene deletion

The peptide endothelin-1 (ET1), which was originally identified as a vasoconstrictor, has emerged as a critical regulator of a number of painful conditions, including inflammatory pain and tumor-associated pain. There is considerable pharmacological evidence supporting a role for endothelin A receptors (ET_A) in mediating ET1-induced pro-algesic functions. ET_A receptors are expressed in small-diameter nociceptive neurons, but also found in a variety of other cell types in peripheral tissues, including immune cells, keratinocytes, endothelial cells, which have the potential to modulate nociception. To elucidate the functional contribution of ET_A receptors expressed in sensory neurons towards the functions of the ET1 axis in pathological pain states, we undertook a conditional gene deletion approach to selectively deplete expression of ET_A in sensory nerves, preserving expression in non-neural peripheral tissues; the expression of ET_B remained unchanged. Behavioural and pharmacological experiments showed that only late nociceptive hypersensitivity caused by ET1 is abrogated upon a loss of ET_A receptors on nociceptors and further suggest that ET1-induced early nociceptive hypersensitivity involves activation of ET_A as well as ET_B receptors in non-neural peripheral cells. Furthermore, in the context of alleviation of cancer pain and chronic inflammatory pain by ET_A receptor antagonists, we observed in corresponding mouse models that the contribution of ET_A receptors expressed in nociceptors is most significant. These results help understand the role of ET_A receptors in complex biological processes and peripheral cell–cell interactions involved in inflammatory and tumor-associated pain.     

Chemical constituents and antimicrobial activity of wood vinegars at different pyrolysis temperature ranges obtained from Eucommia ulmoides Olivers branches

Pyrolysis is a promising approach for converting biomass to solids, liquids, and gases. Herein wood vinegars (WVs) were produced from pyrolysis of Eucommia ulmoides Olivers (EUO) branches in different temperature ranges that were labeled as WV_90∼120 and WV_480∼510. The yield, the physicochemical characteristics, the chemical composition, and the antimicrobial activity of the WVs were comprehensively investigated. During the pyrolysis process, as the temperature increased, the yield of the WVs increased firstly and then decreased, and WV_300∼330 achieved the maximum yield of 236.79 g, accounting for 23.26% of the total amount of raw WVs. However, both the lowest pH value (2.39) and the highest total acid content (12.70%) occurred for WV_270∼300. GC-MS results demonstrated that six components of WVs for WV_300∼330 were phenols, ketones, aldehydes, alcohols, organic acids, and benzenes, while no clear regularity between the contents of each component and the reaction temperature was found. Thereafter, the antimicrobial activity of WVs was tested, and the results showed that the longest inhibition circle diameter of 24.50 mm for Enterobacter aerogenes was obtained for WV_300∼330 indicating an excellent antibacterial activity; the overall inhibitory effects of WVs on bacteria were superior to those of plant pathogens and fungus. Therefore, WV_300∼330 showed a better antimicrobial activity than that of WV_270∼300 in this study. The result could be a reference for the further utilization of WVs in the field of antimicrobial development.

Wood vinegars that showed promising antimicrobial activity for different microorganisms were WV_240–270, WV_270–300, WV_300–330, and WV_450–480, suggesting that the optimal pyrolysis temperature was mainly in the medium temperature range.     

Effects of bosentan on cellular processes involved in pulmonary arterial hypertension: do they explain the long‐term benefit?

Pulmonary arterial hypertension is a rapidly progressing disease characterized by an over‐ expression of endothelin. In addition to its potent pulmonary vasoconstrictor effects, endothelin has been shown to produce many of the aberrant changes, such as hypertrophy, fibrosis, inflammation, and neurohormonal activation that underlie the shortened life span in pulmonary arterial hypertensive patients. The fact that endothelin expression correlates significantly with disease severity and outcome in these patients suggests that endothelin, through binding to both ET _A and ET _B receptor subtypes, is a key causative agent in the pathophysiology of pulmonary arterial hypertension. The orally active dual endothelin receptor antagonist bosentan ¹ competitively antagonizes the binding of endothelin to both endothelin receptor subtypes with high affinity and specificity. In animal models relevant for the pathophysiology of pulmonary hypertension, bosentan not only causes selective pulmonary vasodilation, but also prevents vascular hypertrophy and cardiac remodeling, attenuates pulmonary fibrosis, decreases vascular inflammation, and blunts neuro‐hormonal activation. These experimental data may explain the effects on disease progression and the long‐term benefit observed with bosentan in pulmonary arterial hypertension.     

An open-source method of constructing cloud-free composites of forest understory temperature using MODIS

Surface air temperature (T_air) is a critical driver of ecosystem processes and phenological dynamics, and can be estimated in near-real time with satellite remote sensing. However, persistent cloud cover often creates large spatial and temporal gaps in our observation records. Previous studies have successfully mapped T_air; however, the challenges of mapping forest understory temperatures (T_ust) are relatively unexplored. This study describes a methodology for constructing cloud-free composites of T_ust at 250 m spatial resolution. We used generalized linear models to correlate daily average T_ust with ground-surveyed forest structural characteristics and land surface temperature (LST) obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS). Models were applied to all four daily MODIS overpasses and combined in to a single image to maximize cloud-free spatial coverage. Pixel temperatures within the remaining cloud gaps were estimated using a temporal averaging algorithm that incorporated a novel approach for factoring the relative cloudiness between days. Models predicted T_ust to within 1.5°C (R² ~ 0.87), with an overall final map accuracy having a mean absolute error of 2.2°C. Maps were produced for two growing seasons using in situ observation data from forested sites throughout the Rocky Mountains of Alberta, Canada. By avoiding complex physical models, our procedure is computationally efficient and capable of processing large volumes of data using open-source programming languages and desktop computers.     

Q‐T interval (QTC) in patients with cirrhosis: relation to vasoactive peptides and heart rate

Objective. Prolonged Q‐T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET‐1 and ET‐3) and calcitonin gene‐related peptide (CGRP) in patients with cirrhosis. In addition, we studied problems with HR correction of QT. Material and methods. Forty‐eight patients with cirrhosis and portal hypertension were studied during a haemodynamic investigation. Circulating levels of ETs and CGRP were determined by radioimmunoassays. Correction of QT for HR above 60 beats per min was performed using the methods described by Bazett (QT_C) and Fridericia (QT_F). Results. Prolonged QT_C (above 440?ms), found in 56?% of the patients, was related to the presence of significant portal hypertension and liver dysfunction (p<0.05 to 0.001), but not to elevated ET‐1, ET‐3 or CGRP. When corrected according to Bazett, QT_C showed no significant relation to differences in HR between patients (r = 0.07, ns). QT_F showed some undercorrection of HR (r = ?0.36; p<0.02). During HR variation in the individual patient, QT_C revealed a small but significant overcorrection (2.6?ms per heartbeat per min; p<0.001). This value was significantly (p<0.02) smaller with QT_F (1.2?ms per heartbeat per min). Conclusions. The prolonged QT_C in cirrhosis is related to liver dysfunction and the presence of portal hypertension, but not to the elevated powerful vasoconstrictor (ET‐1) or vasodilator (CGRP, ET‐3) peptides. The problems with correction of the QT for elevated HR in cirrhosis are complex, and the lowest HR should be applied for determination of the QT.     

多b值DWI在脑胶质瘤治疗后近期评价中的应用

目的 探讨应用多b值DWI中不同b值ADC值评估胶质瘤近期治疗效果及鉴别肿瘤进展的价值。方法 对47例经手术病理证实为脑胶质瘤且接受联合放化疗的患者行常规MRI及多b值DWI（b=0、1 000、2 000、3 000 s/mm²）扫描。分别在5种不同b值组合（b值组合分别为：0、1 000 s/mm²,0、2 000 s/mm²,0、3 000 s/mm²,1 000、3 000 s/mm²,2 000、3 000 s/mm²）的ADC图[ADC_{（1 000/0）}、ADC_{（/2 000/0）}、ADC_{（3 000/0）}、ADC_{（3 000/1 000）}、ADC_{（3 000/2 000）}]中测量病灶的平均和最小ADC值（ADC_mean和ADC_min）,计算其相对值（rADC_mean、rADC_min）。比较治疗后不同反应类型（完全有效、部分有效、稳定、进展）间及进展组与非进展组间ADC值的差异,通过ROC曲线分析不同ADC值诊断肿瘤进展的最佳临界值和诊断效能。结果 ADC_{（3 000/0）}、ADC_{（3 000/1 000）}和ADC_{（3 000/2 000）}图中的rADC_mean在不同反应类型间和进展组与非进展组间差异均有统计学意义（P均<0.05）;ADC_{（3 000/1 000）}和ADC_{（3 000/2 000）}图中的ADC_mean在不同反应类型间和进展组与非进展组间差异均有统计学意义（P均<0.05）。ADC_{（3 000/2 000）}图中ADC_mean和rADC_mean诊断肿瘤进展的曲线下面积最大,分别为0.86和0.84,以ADC_mean=408.65×10^-6 mm²/s和rADC_mean=1.12诊断胶质瘤进展的敏感度、特异度分别为89.3%、71.0%和92.9%、77.4%。结论 通过高b值ADC图中病灶的ADC_mean和rADC_mean可较准确地评估胶质瘤的近期治疗效果,并为鉴别胶质瘤术后肿瘤进展提供有价值的信息。     

Endothelium-dependent relaxation counteracting the contractile action of endothelin-1 is partly due to ETB receptor activation

The vasomotor effects of the endothelins (ETs) are mediated by activation of receptor subtypes termed ET_A and ET_B. The present study aimed to characterize the interaction of ET_A and ET_B receptor activation in the cerebral circulation. Ring segments obtained from rat basilar artery were used for measurement of isometric force under resting tension or following precontraction with prostaglandin F_2α. In some segments, the endothelium was removed mechanically. In precontracted arteries, ET-1 elicited contraction only. In the presence of the ET_A receptor antagonist, BQ-123 (10^?5 M), however, ET-1 induced a concentration-related relaxation with a pD₂ value of 8.93±0.16 (mean±SEM,n=15). The relaxant action was abolished following princubation with an ET_B receptor antagonist, IRL-1038 (3×10^?6 M), or with a nitric oxide synthase inhibitor,N ^G-nitro-l-arginine (10^?5 M). These results indicate that the relaxation was mediated by ET_B receptor activation coupled to the release of nitric oxide. Under resting tension, ET-1 elicited concentration-related contraction (pD₂: 8.03±0.04,n=37). In arteries devoid of a functional endothelium, the concentration-effect curve was shifted to the left yielding a pD₂ value of 8.88±0.11 (n=31). Similarly, in endotheliumintact arteries contraction to ET-1 was augmented following nitric oxide synthase inhibition or ET_B receptor blockade with 3×10^?6 M BQ-788 (pD₂: 8.94±0.18,n=19). The results suggested that, in the isolated rat basilar artery, ET-1 induced coactivation of the contraction-mediating ET_A receptor and the relaxation-mediating ET_B receptor. The coactivation resulted in opposing vasomotor effects, but the contraction covered relaxation under normal conditions. However, force development by ET-1 was suppressed by its endothelium-dependent relaxant action.     

亚急性期脑梗死的体素内不相干运动扩散加权成像

目的 探讨体素内不相干运动（IVIM）成像评价亚急性期脑梗死弥散和灌注情况的价值。方法 回顾性分析35例亚急性期脑梗死患者的MR影像资料,包括常规DWI、IVIM成像及三维动脉自旋标记（3D-ASL）序列检查。通过常规DWI序列获得ADC图,IVIM序列获得纯水分子扩散系数（D）图、灌注相关扩散系数（D^*）图、灌注分数（f）图,3D-ASL序列获得脑血流量（CBF）图。分别测量脑梗死灶及对照侧镜像区ADC值、D值、D^*值、f值、CBF值及其相对值（rADC、rD、rD^*、rf、rCBF）。比较脑梗死灶与对照侧镜像区各参数的差异,并分析rADC值与rD、rD^*、rf值的相关性及rCBF值与rD、rD^*、rf值的相关性。结果 脑梗死灶ADC、D、D^*、f、CBF值均较对照侧镜像区减低（P均<0.05）。rADC值与rD、rf值呈正相关（r=0.687、0.601,P=0.005、0.018）;rCBF值与rf值呈正相关（r=0.581,P=0.022）。结论 IVIM成像能同时提供亚急性期脑梗死的灌注及弥散信息,有助于进一步阐明亚急性期脑梗塞的机制。     

Evidence that both ETA and ETB receptor subtypes are involved in the in vivo aldosterone secretagogue effect of endothelin-1 in rats

Endothelins (ET) are a family of vasoconstrictor peptides, secreted by vascular endothelium, which act through two main subtypes of receptors: ET_A and ET_B. ET-1 is known to stimulate aldosterone (ALDO) secretion by adrenal zona glomerulosa (ZG), and in vitro its effect was recently found to be exclusively mediated by ET_B receptors. In this study the involvement of ET_A and ET_B in the mediation of the in vivo acute ALDO secretagogue action of ET-1 was investigated by the use of their selective antagonists BQ-123 and BQ-788, respectively. The bolus intraperitoneal administration of ET-1 dose-dependently raised both basal and angiotensin II (ANG II)-enhanced plasma ALDO concentration (PAC) in rats. Both antagonists counteracted the stimulatory effect of ET-1 on basal PAC, and when administered together completely annulled it. Conversely, only BQ-788 reversed the effect of ET-1 on ANG II-enhanced PAC. ET-1 increased systolic blood pressure (BP) in normal rats, but not in animals simultaneously administered ANG II. The hypertensive effect of ET-1 was completely abolished by BQ-123, and not affected by BQ-788. In light of these findings the following conclusions can be drawn: (i) the in vivo ALDO secretagogue action of ET-1 is mediated by both ET_A and ET_B, this latter subtype of ET receptors playing a major role; and (ii) the mechanism whereby ET_A participates in this in vivo effect of ET-1 is indirect, and probably connected with the ET-1-induced rise in BP and adrenal blood flow.     

Rapid error assessment for quantitative estimations from Landsat 7 gap-filled images

The failure of the Scan Line Corrector (SLC) of the Landsat ETM+ (Enhanced Thematic Mapper Plus) instrument in 2003 had resulted in missing values for 22% of each scene. As the remaining pixels were of high quality, several procedures had been developed to fill the gaps and increase the usability of the SLC-off images. In this letter, a methodology is presented to assess the error when estimating quantitative parameters from gap-filled Landsat 7 images. The error from the gap-filling procedure was estimated using an external reference image. The methodology was applied in a Mediterranean river basin using two types of gap-filling methods and the error was estimated for leaf area index (LAI), actual evapotranspiration (ET_a) and soil moisture in the rootzone (SM_rz), three remotely sensed products which are commonly used in hydrological studies. The results suggest that the interpolation method had lower errors in all examined products. The proposed methodology is an imperative step that each user of gap-filled products could use to estimate the associated error before using the maps.     

Mechanical active compression–decompression cardiopulmonary resuscitation (ACD-CPR) versus manual CPR according to pressure of end tidal carbon dioxide (PETCO2) during CPR in out-of-hospital cardiac arrest (OHCA)

AimIn animal and human studies, measuring the pressure of end tidal carbon dioxide (P_ETCO₂) has been shown to be a practical non-invasive method that correlates well with the pulmonary blood flow and cardiac output (CO) generated during cardiopulmonary resuscitation (CPR). This study aims to compare mechanical active compression–decompression (ACD) CPR with standard CPR according to P_ETCO₂ among patients with out-of-hospital cardiac arrest (OHCA), during CPR and with standardised ventilation.MethodsThis prospective, on a cluster level, pseudo-randomised pilot trial took place in the Municipality of Göteborg. During a 2-year period, all patients aged >18 years suffering an out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology were enrolled. The present analysis included only tracheally intubated patients in whom P_ETCO₂ was measured for 15 min or until the detection of a pulse-giving rhythm.ResultsIn all, 126 patients participated in the evaluation, 64 patients in the mechanical chest compression group and 62 patients in the control group. The group receiving mechanical ACD-CPR obtained the significantly highest P_ETCO₂ values according to the average (p = 0.04), initial (p = 0.01) and minimum (p = 0.01) values. We found no significant difference according to the maximum value between groups.ConclusionIn this hypothesis generating study mechanical ACD-CPR compared with manual CPR generated the highest initial, minimum and average value of P_ETCO₂. Whether these data can be repeated and furthermore be associated with an improved outcome after OHCA need to be confirmed in a large prospective randomised trial.     

DCE-MRI定量参数全域直方图鉴别诊断乳腺导管原位癌与乳腺导管原位癌伴微浸润

目的 探讨动态增强MRI（DCE-MRI）定量参数全域直方图鉴别诊断乳腺导管原位癌（DCIS）与 DCIS伴微浸润（DCIS-Mi）的价值。方法 收集41例DCIS-Mi和37例DCIS患者,术前行DCE-MRI,计算容积转运常数（K^trans）、速率常数（K_ep）、血浆容积分数（V_p）,并记录其全域直方图参数,包括平均值、中位数及10%、25%、50%、75%、90%分位数（P₁₀、P₂₅、P₅₀、P₇₅、P₉₀）。比较DCIS-Mi和DCIS组间各参数差异,并分析最佳参数的诊断效能。结果 DCIS-Mi组K^trans参数中的平均值及各百分位数,K_ep参数中的平均值、中位数、P₅₀、P₇₅、P₉₀,V_p参数中的平均值、中位数、P₂₅、P₅₀、P₇₅均高于DCIS组（P均<0.05）。Logistic回归结果显示K^trans平均值、K^trans-P₂₅、K^trans-P₅₀、K^trans-P₇₅、K^trans-P₉₀、K_ep-P₅₀、K_ep-P₇₅、K_ep-P₉₀、V_p平均值、V_p-P₇₅为诊断DCIS-Mi的最佳变量,且其诊断DCIS-Mi的ROC曲线AUC均>0.80。联合变量Logistic回归模型具有最高的AUC（0.968）,其临界值、敏感度和特异度分别为2.152、0.962和0.947。结论 DCE-MRI全域直方图分析能量化反映肿瘤特征,准确诊断及鉴别诊断乳腺DCIS与DCIS-Mi。     

Bioequivalence evaluation of two capsule formulations of amoxicillin in healthy adult male bangladeshi volunteers: A single-dose, randomized, open-label, two-period crossover study

Background: Amoxicillin, a semisynthetic penicillin antibiotic, is widely prescribed in Bangladesh due to its extended spectrum and its rapid and extensive oral absorption with good tolerability. Although a number of generic oral formulations of amoxicillin are available in Bangladesh, a study of the bioequivalence and pharmacokinetic properties of these formulations has not yet been conducted in a Bangladeshi population.Objective: The aim of this study was to assess the pharmacokinetic properties and bioequivalence of 2 formulations of amoxicillin 500-mg capsules (test, SK-mox^®; reference, Amoxil-Bencard^®) using serum data.Methods: This single-dose, randomized, open-label, 2-period crossover study was conducted in healthy male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were assigned to receive the test or the reference drug as a single-dose, 500-mg capsule under fasting conditions after a 1-week washout period. After oral administration, blood samples were collected and analyzed for amoxicillin concentration using a validated high-performance liquid chromatography method. The pharmacokinetic parameters were determined using a noncompartmental method. The formulations were considered bioequivalent if the natural log-transformed ratios of pharmacokinetic parameters were within the predetermined equivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement.Results: Twenty-four healthy adult male Bangladeshi volunteers (mean [SD] age, 26.92 [3.37] years; age range, 23–34 years; mean [SD] body mass index, 23.O9 [1.58] kg/m²) participated in the study. Using serum data, the values obtained for the test and reference formulations, respectively, were as follows: C_max, 9.85 (2.73) and 10.63 (2.12) μg/mL; T_max, 1.29 (0.58) and 1.33 (0.49) hours; and AUC_0–12, 27.09 (7.62) and 28.56 (6.30) μg/mL · h⁻¹. No period, sequence, or formulation effects were observed; however, significant variation was found among subjects with regard to AUC_0–12 (P < 0.001), AUC_0−∞ (P = 0.002), area under the moment curve (AUMC) from 0 to 12 hours (P < 0.001), and AUMC_0−∞ (P = 0.017). All CIs for the parameters measured were within the FDA-accepted limits of 80% to 125%.Conclusion: The present study suggests that the test 500-mg amoxicillin capsule was bioequivalent to the reference 500-mg capsule according to the FDA regulatory definition, in this population of healthy adult male Bangladeshi volunteers.     

Identifying patterns and hotspots of global land cover transitions using the ESA CCI Land Cover dataset

Land use/land cover change is a continuing research focus, not only because of its ecological and environmental effects but also because of the difficulties with accurate change detection and analysis uncertainty. The principal difficulty is the lack of a long time series of annual global land cover maps at a fine resolution. A new global long-term time series of annual datasets called the European Space Agency (ESA) Climate Change Initiative Land Cover (CCI-LC) has been published, making it possible to detect the global land cover changes. Using this ESA CCI-LC product from 1992–2015, we quantified the annual transitions of land cover change globally with the trajectory analysis method, analyzed the changes patterns and identified the land cover change hotspots. The total land cover change area for the world was 5.99 million km², amounting to only 3.36% of the total continental area. Most changes happened in forest and cropland, accounting 32% of all the land cover changes. Most land cover changes happened in tropical ecoregions. Grassland changes were mainly distributed in the temperate ecoregions, while cropland expansion occurred mainly in the tropical or subtropical ecoregions. The hotspots identified in this paper could provide target areas for further research.