Bayesian consensus clustering for multivariate longitudinal data

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.     

基于代谢组学探讨艾灸关元穴对老年大鼠肾能量代谢的影响＊

目的 通过UHPLC-Q-TOF-MS代谢组学探讨艾灸关元穴对老年大鼠肾代谢物的影响，进而为艾灸关元穴的作用机制提供参考。方法 将8月龄SD雄性大鼠设为成年对照组（8只），21月龄SD雄性大鼠随机分为老年对照组（8只）、老年金匮肾气丸组（7只）、老年艾灸组（8只）。老年金匮肾气丸组每日按体重给药，老年艾灸组每日艾灸关元穴15 min，均每周5天。实验持续13周后检测大鼠肾组织线粒体呼吸耗氧速率、琥珀酸脱氢酶（SDH）活性以及血清肾功能指标，观察肾脏病理变化，结合UHPLC-Q-TOF-MS技术对大鼠的肾组织进行代谢轮廓分析，筛选代谢差异物并进行鉴定。结果 与老年对照组比较，老年艾灸组大鼠肾线粒体的呼吸耗氧速率和SDH酶的活力显著提高（P<0.01）。代谢组学结果显示，肾组织中筛选出13个共同差异化合物，分别是丁酸十二烷基酯、亚油酰胺、5-甲基四氢叶酸、PC（16∶0/22∶5（7Z，10Z，13Z，16Z，19Z））、6，8-二羟基嘌呤、1，2，3-丙烷三羧酸、3-（4-甲氧基苯基）-2-氧代丙酸、吲哚-3-乙酰甘氨酸、亚麻油酸、9，10-环氧十八烷酸、二十二碳五烯酸（22n-6）、牛磺胆酸、LysoPS （18∶0/0∶0）。结论 艾灸关元穴可通过调控老年大鼠的牛磺酸和亚牛磺酸代谢、α-亚麻酸代谢、亚油酸代谢、甘油磷脂代谢来调节肾的能量代谢。     

Adverse events due to unnecessary radiation exposure in medical imaging reported in Finland

IntroductionAdverse events in radiology are quite rare, but they do occur. Radiation safety regulations and the law obligate organizations to report certain adverse events, harm and near misses, especially events related to patients' health and safety. The aim of this study was to describe and analyse incidents related to radiation safety issues reported in Finland.MethodsThe data were collected from incident reports documented by radiology personnel concerning notifications of abnormal events in medical imaging made to the Radiation and Nuclear Safety Authority between 2010 and 2017. During these eight years, 312 reports were submitted. Only events reported from radiology departments were included; nuclear medicine, radiotherapy and animal radiology cases were excluded. The final number of reports was 293 (94%).ResultsThe majority of the 293 approved reports were related to computed tomography (CT, 68.3%) and to X-ray examinations (27.6%). Altogether 82.9% of those irradiated were adults, most of whom were exposed to unnecessary radiation through CT (86.5%), 5.5% were children, and 4.4% pregnant women. The most common effective dose of unnecessary radiation was 1 mSv or less (89.7% of all examinations). The highest effective doses were reported in CT (from under 1 mSv–20 mSv and above). The reasons for the adverse events were incorrect identification (32%), incorrect procedure, site or side (30%); and human errors or errors of knowledge (20%).ConclusionAdverse events occurred especially in CT examinations. It is important to collect and analyse incident data, assess the harmful events, learn from them and aim to reduce adverse events.Implications for practiceThis study emphasizes the need for radiological personnel to obtain evidence-based information on adverse events and focus on training to improve patient safety.     

Physical laws of cholesterol gallstone fragmentation

Efficient fragmentation is the most important prerequisite for successful treatment of gallstones by extracorporeally induced shock waves. No data are available on the amount of energy necessary for stone disintegration and on the threshold energy below which no further fragmentation occurs. We therefore performed an in vitro investigation on human cholesterol gallstones to elucidate physical laws governing shock-wave lithotripsy. First, the focal pressure of the lithotripter was measured to calculate the energy traversing a stone. Second, 96 gallstones from 16 gall bladders were analysed with respect to physicochemical composition, radiological features and ultrasound before fragmentation was performed. Energy for stone disintegration was constant within each stone family but varied between 4.6 J mL^?1 and 36.8 J mL^?1 in different families. This energy correlated linearly with stone volume. None of the radiological and physicochemical factors revealed a clear-cut correlation of the different energies necessary for similar stone disintegration. The threshold energy differed between 0.26 mJ and 1.04 mJ per pulse. In conclusion, stone volume was the best parameter predicting stone fragmentation. However, in cholesterol stones with a similar composition the required energy per volume varies considerably together with the threshold energy. Radiological and ultrasound parameters appear to be of minor importance in explaining these differences.     

Multivariate modelling of responses to conditional items: New possibilities for latent class analysis

Questionnaire data may contain missing values because certain questions do not apply to all respondents. For instance, questions addressing particular attributes of a symptom, such as frequency, triggers or seasonality, are only applicable to those who have experienced the symptom, while for those who have not, responses to these items will be missing. This missing information does not fall into the category ‘missing by design’, rather the features of interest do not exist and cannot be measured regardless of survey design. Analysis of responses to such conditional items is therefore typically restricted to the subpopulation in which they apply. This article is concerned with joint multivariate modelling of responses to both unconditional and conditional items without restricting the analysis to this subpopulation. Such an approach is of interest when the distributions of both types of responses are thought to be determined by common parameters affecting the whole population. By integrating the conditional item structure into the model, inference can be based both on unconditional data from the entire population and on conditional data from subjects for whom they exist. This approach opens new possibilities for multivariate analysis of such data. We apply this approach to latent class modelling and provide an example using data on respiratory symptoms (wheeze and cough) in children. Conditional data structures such as that considered here are common in medical research settings and, although our focus is on latent class models, the approach can be applied to other multivariate models. Copyright © 2009 John Wiley & Sons, Ltd.     

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> var. <Emphasis Type="Italic">Otaksa</Emphasis>, with special reference to its antimalarial activity

Febrifugine and isofebrifugine alkaloid mixtures extracted from the leaves and buds of Hydrangea macrophylla var. Otaksa, collected during different months, in Japan, were quantified using high-performance liquid chromatography. Leaves collected during the flowering season, namely from June to August, contained 0.16–0.31 mg/g of the alkaloid mixture, whereas those collected from September to December had less than 0.03 mg/g of the mixture. However, extracts of buds harvested from October to February contained a consistently larger amount (more than 0.49 mg/g) of the alkaloids. Hot-water extracts from the leaves and buds collected during different seasons were evaluated for antimalarial activity against Plasmodium yoelii 17XL in mice. The extract of leaves collected in August demonstrated high antimalarial activity, and all mice that received the extract survived the infection. In contrast, the extract of leaves collected in December showed little activity. The extract of buds collected in December cleared parasites, but with subsequent mortality to mouse. The present results show that the amount of antimalarial agent—febrifugine and isofebrifugine mixture—in H. macrophylla var. Otaksa is both part- and season-dependent, suggesting that the choice of plant parts and their harvesting season are important factors worth considering in the pharmacological use of medicinal plants.     

Mechanical energy absorption in human hand-arm exposed to sinusoidal vibration

Summary A possible basis for risk assessment of human exposure to vibration when using hand-held tools may be to determine the amount of mechanical energy that is absorbed by the hand-arm system. The aim of this investigation was to study the absorption of mechanical energy in the human hand-arm system during exposure to sinusoidal vibration within the frequency range of 20 to 1500 Hz. A handle, specially designed for this type of experiments, was used during the measurements. The influence of various experimental conditions, such as three different hand-arm postures, grip force (25–75 N) and vibration levels (27–53 mm/s_rms), were studied on eight subjects. The outcome clearly shows that the energy absorption properties of the human hand-arm system are more or less dependent on all of the experimental conditions studied, but mainly to the frequency of the vibration stimuli. Furthermore, the results indicate a non-linear relationship between the energy absorbed and all other variables studies.     

不同海拔高度严重烧伤延迟复苏大鼠脑组织中能量负荷的变化及其意义

目的：探讨不同海拔高度严重烧伤延迟复苏大鼠脑组织能量负荷变化及其意义。方法：以120只雄性Wistar大鼠建立高原（海拔3800m）实验模型（TBSA30％，Ⅲ度），随机分为延迟、即时复苏组和正常对照组，分别于伤后1、6、12、24、72h及7d取材。兰州地区取相等数量动物重复实验。应用高效液相色谱法检测脑组织中AMP、ADP、ATP的含量，并计算能量负荷。结果：能量负荷在高原正常对照组与兰州地区正常对照组差异显著（P〈0．01）。高原烧伤后脑组织能量负荷与对照组相比均降低，即时复苏组伤后早期即出现显著变化（P〈0．01），伤后72h开始恢复，伤后7d差异无显著，延迟复苏组伤后7d仍星显著差异（P〈0．01）。与即时复苏组比较伤后6～24h无显著差异，伤后72h～7d呈显著性差异（P〈0．01）。高原地区各时相点与兰州地区比较，EC值均降低，除即时复苏组6h外，具有统计学意义。结论：不同海拔高度严重烧伤延迟复苏大鼠脑组织能量负荷的改变一定程度上反映了脑损伤的严重程度。     

地黄合剂降血糖作用的实验性研究

本文通过用四氧嘧啶复制小白鼠糖尿病模型,以血清中血糖及胰岛素水平为指标,研究了地黄合剂对高糖动物的降血糖作用。结果表明,注射四氧嘧啶前小白鼠血糖为173.47±5.23mg/100ml注射后血糖升高至419.78±22.70mg/100ml(P<0.01),差异有高度显著性。实验组服用地黄合剂后,血糖值从410.25±2739mg/100ml下降至313.51±29.39mg/100ml(P<0.05)差异有显著性。因而认为地黄合剂对于四氧嘧啶性糖尿病有显著的降血糖作用。     

Proline reduces brain cytochrome c oxidase: prevention by antioxidants

In the present study, we initially investigated the in vivo (acute and chronic) and in vitro effects of proline on cytochrome c oxidase (complex IV) activity in rat cerebral cortex to test the hypothesis that proline might alter energy metabolism and that this alteration could be provoked by oxidative stress. The action of alpha-tocopherol and ascorbic acid on the effects produced by proline was also evaluated. For acute administration, 29- and 60-day-old rats received one subcutaneous injection of proline (18.2 micromol/g body weight) or an equivalent volume of 0.9% saline solution (control) and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously twice a day at 10h intervals from the 6(th) to the 28(th) day of age. Rats were sacrificed 12h (29(th)) or 31 days (60(th)) after the last injection. Results showed that acute administration of proline significantly diminished the activity of cytochrome c oxidase in the cerebral cortex of 29- and 60-day-old rats. On the other hand, chronic hyperprolinemia reduced this complex activity only on day 29, but not on the 60(th) day of life. In another set of experiments, 22-day-old rats or 53-day-old rats were pretreated for 1 week with daily intraperitoneal administration of alpha-tocopherol (40 mg/kg) and ascorbic acid (100mg/kg) or saline. Twelve hours after the last antioxidant injection, rats received a single injection of proline or saline and were killed 1h later. In parallel to chronic treatment, rats received a daily intraperitoneal injection of alpha-tocopherol and ascorbic acid from the 6(th) to the 28(th) day of life and were killed 12h after the last injection. Results showed that the pretreatment with alpha-tocopherol and ascorbic acid before acute proline administration or concomitant to chronic proline administration significantly prevented these effects. We also observed that proline (3.0 microM-1.0 mM) when added to the incubation medium (in vitro studies) did not alter cytochrome c oxidase activity. Data suggest that the inhibitory effect of proline on cytochrome c oxidase activity is possibly associated with oxidative stress and that this parameter may be involved in the brain dysfunction observed in hyperprolinemia.