The Importance of Venous Return in Starling‐Like Control of Rotary Ventricular Assist Devices

Rotary ventricular assist devices (VADs) are less sensitive to preload than the healthy heart, resulting in inadequate flow regulation in response to changes in patient cardiac demand. Starling‐like physiological controllers (SLCs) have been developed to automatically regulate VAD flow based on ventricular preload. An SLC consists of a cardiac response curve (CRC) which imposes a nonlinear relationship between VAD flow and ventricular preload, and a venous return line (VRL) which determines the return path of the controller. This study investigates the importance of a physiological VRL in SLC of dual rotary blood pumps for biventricular support. Two experiments were conducted on a physical mock circulation loop (MCL); the first compared an SLC with an angled physiological VRL (SLC‐P) against an SLC with a vertical VRL (SLC‐V). The second experiment quantified the benefit of a dynamic VRL, represented by a series of specific VRLs, which could adapt to different circulatory states including changes in pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed physiological VRL which was calculated at rest. In both sets of experiments, the transient controller responses were evaluated through reductions in preload caused by the removal of fluid from the MCL. The SLC‐P produced no overshoot or oscillations following step changes in preload, whereas SLC‐V produced 0.4 L/min (12.5%) overshoot for both left and right VADs. Additionally, the SLC‐V had increased settling time and reduced controller stability as evidenced by transient controller oscillations. The transient results comparing the specific and standard VRLs demonstrated that specific VRL rise times were improved by between 1.2 and 4.7 s ( = 3.05 s), while specific VRL settling times were improved by between 2.8 and 16.1 seconds ( = 8.38 s) over the standard VRL. This suggests only a minor improvement in controller response time from a dynamic VRL compared to the fixed VRL. These results indicate that the use of a fixed physiologically representative VRL is adequate over a wide variety of physiological conditions.     

In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

Determinants of Regional Variation in Health Expenditures in Germany

Health care expenditure in Germany shows clear regional differences. Such geographic variations are often seen as an indicator for inefficiency. With its homogeneous health care system, low co‐payments and uniform prices, Germany is a particularly suited example to analyse regional variations. We use data for the year 2011 on expenditure, utilization of health services and state of health in Germany's statutory health insurance system. This data, which originate from a variety of administrative sources and cover about 90% of the population, are enriched with a wealth of socio‐economic variables, data on pollutants, prices and individual preferences. State of health and demography explains 55% of the differences as measured by the standard deviation while all control variables account for a total of 72% of the differences at county level. With other measures of variation, we can account for an even greater proportion. A higher proportion of variation than usually supposed can thus be explained. Whilst this study cannot quantify inefficiencies, our results contradict the thesis that regional variations reflect inefficiency. Copyright © 2015 John Wiley & Sons, Ltd.     

老年轻度认知障碍患者血清瘦素、甲状腺激素水平与局部脑血流量关系的研究

目的 通过检测老年轻度认知障碍（MCI）患者血清瘦素（LEP）、甲状腺激素水平，分析其与局部脑血流量（rCBF）的关系。方法 选择本院收治的128 例老年MCI 患者，另选健康者128 例作为对照组。检测血清LEP、甲状腺激素、大脑各区域rCBF 水平并分析其相关性。结果 老年MCI 组患者左右侧额叶、右侧颞叶、左侧顶叶、左右侧基底节区域脑血流量[（43.81±8.62）mL/（100 g·min）、（43.24±7.93）mL/（100 g·min）、（45.14±6.98）mL/（100 g·min）、（45.86±6.77）mL/（100 g·min）、（67.95±8.52）mL/（100 g·min）、（68.36±8.34）mL/（100 g·min）]低于对照组[（46.39±8.31）mL/（100 g·min）、（46.52±8.56）mL/（100 g·min）、（47.37±7.04）mL/（100 g·min）、（48.25±6.98）mL/（100 g·min）、（70.34±8.96）mL/（100 g·min）、（70.58±8.57）mL/（100 g·min）]（P＜0.05）。老年MCI 组患者血清LEP、T3、FT3 水平[（4.87±1.56）μg/L、（1.21±0.16）nmol/L、（3.04±0.36）pmol/L]低于对照组[（11.45±3.92）μg/L、（1.68±0.21）nmol/L、（4.82±1.21）pmol/L]（P＜0.05），TSH 水平为（2.78±0.75）IU/mL，高于对照组的（1.13±0.38）IU/mL（P＜0.05）。老年MCI 患者血清LEP 水平与左侧额叶、右侧颞叶、左侧顶叶rCBF 呈正相关（r=0.452、0.537、0.544，P 均＜0.05），T3 水平与左侧额叶、右侧颞叶rCBF 呈正相关（r=0.427、0.521，P 均＜0.05），FT3 水平与右侧颞叶rCBF 呈正相关（r=0.492，P＜0.05），TSH 水平与左侧额叶、右侧颞叶rCBF 呈负相关（r=-0.463、-0.489，P 均＜0.05）。结论 老年MCI 患者血清中LEP、T3、FT3 水平降低，TSH 水平升高，且与不同区域rCBF 有相关性，可通过调控脑血管功能影响rCBF 变化水平。     

SI和DBP对女性产后出血的风险预测效果

目的考察休克指数(shock index,SI)和舒张压(diastolic blood pressure,DBP)对女性产后出血的风险预测效果。方法选取2016年1月～2018年12月在我院行产检并分娩的320例产后出血孕妇作为研究组,另外选取同期进行正常分娩的健康孕妇240例作为对照组,比较两组患者的一般临床资料、血红蛋白(hemoglobin,Hb)、舒张压(diastolic blood pressure,DBP)、收缩压(systolic blood pressure,SBP)、心率(heart rate,HR)及休克指数(shock index,SI),并采用Ordinal逻辑回归分析各参数对产后出血的风险预警。结果两组患者在年龄、孕周、BMI及新生儿体重相比,差异无统计学意义(P0.05),而孕次相比,差异具有统计学意义(P0.05);与对照组产后24 h相比,研究组产后24 h患者的DBP、SBP及Hb均显著降低,而HR和SI显著升高(P0.05);与对照组产前相比,产后24 h患者的SBP、HR及SI显著降低(P0.05);与研究组产前相比,产后24 h患者的DBP、SBP、HR及Hb均显著降低,而SI显著升高,差异具有统计学意义(P0.05);Ordinal逻辑回归分析结果显示,休克指数和舒张压对产后出血具有预警作用(P0.05)。结论休克指数和舒张压可作为评估女性产后出血的风险预测指标,临床应密切监护。     

从“血不利则为水”探讨乳腺癌相关淋巴水肿

导致血不利的原因一是不足,即由于气、血、津、液等物质的缺乏致无源行血;一是不通,即水、湿、痰、饮、瘀、食积、火郁、内风、外伤等病理因素阻滞,致血行不畅。血瘀经脉之内,则水亦瘀积脉中,致脉络胀满,形成水肿。乳腺癌术后患者,金刃本已损伤血脉,术后的放疗、化疗又属祛邪之法,故机体元气受损,气虚无力行血,血运行不畅,导致患侧上肢水肿。故治疗乳腺癌相关淋巴水肿时,应当血水同治,即活血利水之法要贯穿始终。先病血而后病水者,可以活血化瘀为主,利水为辅;先病水后病血者,则以利水消肿为主,酌加活血养血之品。但需要注意的是:①临证时切不可拘泥于单纯的活血利水法,而忽视乳腺癌相关淋巴水肿(breast cancer related lymphedema,BCRL)患者机体本身的状况。②临证勿忽视五脏与血、水的关系,以及肺、脾、肾、三焦与水肿的内在关系。③可多种方法联合运用,审证求因,标本同治。BCRL术后宜补气活血,通脉利水;术后兼化疗者可疏肝健脾、利水消肿;早期可在活血利水基础上,侧重利湿消肿,后期多湿聚为痰,治疗侧重化痰软坚。     

Ultrasound-Assist Extrusion Methods for the Fabrication of Polymer Nanocomposites Based on Polypropylene/Multi-Wall Carbon Nanotubes

Isotactic polypropylenes (iPP) with different melt flow indexes (MFI) were used to fabricate nanocomposites (NCs) with 10 wt % loadings of multi-wall carbon nanotubes (MWCNTs) using ultrasound-assisted extrusion methods to determine their effect on the morphology, melt flow, and electrical properties of the NCs. Three different types of iPPs were used with MFIs of 2.5, 34 and 1200 g/10 min. Four different NC fabrication methods based on melt extrusion were used. In the first method melt extrusion fabrication without ultrasound assistance was used. In the second and third methods, an ultrasound probe attached to a hot chamber located at the exit of the die was used to subject the sample to fixed frequency and variable frequency, respectively. The fourth method is similar to the first method, with the difference being that the carbon nanotubes were treated in a fluidized air-bed with an ultrasound probe before being used in the fabrication of the NCs with no ultrasound assistance during extrusion. The samples were characterized by MFI, Optical microscopy (OM), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), electrical surface resistivity, and electric charge. MFI decreases in all cases with addition of MWCNTs with the largest decrease observed for samples with the highest MFI. The surface resistivity, which ranged from 10¹³ to 10⁵ Ω/sq, and electric charge, were observed to depend on the ultrasound-assisted fabrication method as well as on the melt flow index of the iPP. A relationship between agglomerate size and area ratio with electric charge was found. Several trends in the overall data were identified and are discussed in terms of MFI and the different fabrication methods.