A new approach for evaluating flexible working hours

Recent studies on flexible working hours show at least some of these working time arrangements seem to be associated with impairing effects of health and well-being. According to available evidence, variability of working hours seems to play an important role. The question, however, is how this variability can be assessed and used to explain or predict impairments. Based on earlier methods used to assess shift-work effects, a time series analysis approach was applied to the matter of flexible working hours. Data on the working hours of 4 week's length of 137 respondents derived from a survey on flexible work hours involving 15 companies of different production and service sectors in Germany were converted to time series and analyzed by spectral analysis. A cluster analysis of the resulting power spectra yielded 5 clusters of flexible work hours. Analyzing these clusters for differences in reported impairments showed that workers who showed suppression of circadian and weekly rhythms experienced severest impairments, especially in circadian controlled functions like sleep and digestion. The results thus indicate that analyzing the periodicity of flexible working hours seems to be a promising approach for predicting impairments which should be investigated further in the future.     

三种输尿管镜治疗输尿管上段结石的疗效比较

目的:比较半硬性输尿管镜、输尿管软镜、孙氏末段可弯输尿管镜治疗输尿管上段结石的临床疗效,为临床上治疗方式的选择提供参考。方法:回顾性分析2015年8月到2017年12月间于上海市第十人民医院泌尿外科因输尿管上段结石行输尿管镜下钬激光治疗的515例患者的临床资料。按照所用输尿管镜类型分为3组:硬镜组(给予半硬性输尿管镜治疗)297例,软镜组172例(给予输尿管软镜治疗),孙氏镜组(给予孙氏末段可弯输尿管镜治疗)46例。比较三组的手术时间、一期清石率、术后住院时间及术中、术后并发症。结果:硬镜组、软镜组、孙氏镜组清石率分别为81.5%、94.2%、95.7%,其中软镜组、孙氏镜组清石率显著高于硬镜组(P0.05)。硬镜组、软镜组、孙氏镜组术中并发症发生率分别为18.9%、5.8%、4.3%,其中硬镜组术中并发症发生率显著高于软镜组和孙氏镜组(P0.05),三组术后并发症发生率整体比较差异无统计学意义(P0.05)。硬镜组、软镜组、孙氏镜组平均手术时间分别为(28.6±6.2)min、(49.4±12.4)min、(26.1±6.5)min,软镜组平均手术时间显著高于硬镜组及孙氏镜组,差异有统计学意义(均P0.05)。硬镜组、软镜组、孙氏镜组平均住院时间分别为(5.4±3.2)d、(6.7±5.7)d、(5.0±2.5)d,软镜组住院时间显著高于硬镜组和孙氏镜组,差异有统计学意义(均P0.05)。结论:软镜清石效果和手术安全性较硬镜更有优势,但手术耗时长,患者术后住院时间长。孙氏镜有望成为治疗输尿管上段结石的更佳选择。     

Robustness of individual and marginal model-based estimates: A sensitivity analysis of flexible parametric models

BackgroundFlexible parametric survival models (FPMs) are commonly used in epidemiology. These are preferred as a wide range of hazard shapes can be captured using splines to model the log-cumulative hazard function and can include time-dependent effects for more flexibility. An important issue is the number of knots used for splines. The reliability of estimates are assessed using English data for 10 cancer types and the use of online interactive graphs to enable a more comprehensive sensitivity analysis at the control of the user is demonstrated.MethodsSixty FPMs were fitted to each cancer type with varying degrees of freedom to model the baseline excess hazard and the main and time-dependent effect of age. For each model, we obtained age-specific, age-group and internally age-standardised relative survival estimates. The Akaike Information Criterion and Bayesian Information Criterion were also calculated and comparative estimates were obtained using the Ederer II and Pohar Perme methods. Web-based interactive graphs were developed to present results.ResultsAge-standardised estimates were very insensitive to the exact number of knots for the splines. Age-group survival is also stable with negligible differences between models. Age-specific estimates are less stable especially for the youngest and oldest patients, of whom there are very few, but for most scenarios perform well.ConclusionAlthough estimates do not depend heavily on the number of knots, too few knots should be avoided, as they can result in a poor fit. Interactive graphs engage researchers in assessing model sensitivity to a wide range of scenarios and their use is highly encouraged.     

Multi-component model of intramural hematoma

A novel multi-component model is introduced for studying interaction between blood flow and deforming aortic wall with intramural hematoma (IMH). The aortic wall is simulated by a composite structure submodel representing material properties of the three main wall layers. The IMH is described by a poroelasticity submodel which takes into account both the pressure inside hematoma and its deformation. The submodel of the hematoma is fully coupled with the aortic submodel as well as with the submodel of the pulsatile blood flow. Model simulations are used to investigate the relation between the peak wall stress, hematoma thickness and permeability in patients of different age. The results indicate that an increase in hematoma thickness leads to larger wall stress, which is in agreement with clinical data. Further simulations demonstrate that a hematoma with smaller permeability results in larger wall stress, suggesting that blood coagulation in hematoma might increase its mechanical stability. This is in agreement with previous experimental observations of coagulation having a beneficial effect on the condition of a patient with the IMH.     

Advances in organic electro-optic materials and processing

Frequency-agile, femtosecond Hyper-Rayleigh scattering measurements are used to test the utility of density functional theory calculations for suggesting chromophore structures with improved molecular first hyperpolarizability, β. A tricyanopyrroline acceptor is shown to yield a factor of approximately three improvement over the commonly used tricyanofuran acceptor. The combination of improved chromophores and incorporation of chromophores into novel nanostructured lattices is leading to routine realization of electro-optic coefficients greater than 100 pm/V at telecommunication wavelengths. In this communication, the use of nanoimprint lithography to stamp out active and passive optical circuitry is also demonstrated. The potential for low-cost, mass production of electro-optic devices, including conformal and flexible devices, is suggested.     

输尿管软镜对肾结石患者肾损伤因子、凝血功能及氧化应激的影响

目的:探讨输尿管软镜对肾结石患者肾损伤因子、凝血功能及氧化应激的影响。方法:回顾性分析2018年9月～2019年9月期间我院收治的200例肾结石患者的临床资料,根据手术方式的不同将患者分为A组(n=100,经皮肾镜取石术)和B组(n=100,输尿管软镜取石术),比较两组患者围术期指标、肾损伤因子、凝血功能及氧化应激指标,并记录两组围术期并发症发生情况。结果:B组手术时间、住院时间短于A组,术中出血量少于A组(P0.05);两组患者结石清除率比较无差异(P0.05)。两组术后1 d血清肌酐(Scr)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)及半胱氨酸蛋白酶抑制剂C(Cys C)水平均升高,但B组低于A组(P0.05)。两组术后1 d的凝血反应时间(R值)、血凝块形成的时间(K值)均下降,但B组高于A组(P0.05);两组术后1 d的血块生成率(α角)及最大宽度值(MA值)均升高,但两组比较差异无统计学意义(P0.05)。两组术后1 d丙二醛(MDA)升高,超氧化物歧化酶(SOD)降低(P0.05);B组术后1 d的MDA高于A组,SOD则低于A组(P0.05)。两组术后并发症发生率对比无统计学差异(P0.05)。结论:与经皮肾镜取石术相比,输尿管软镜取石术可获得相当的治疗效果,其在改善肾功能、凝血功能及氧化应激等方面效果更佳,且不增加并发症发生率,临床应用价值较高。     

Applications of the molecular dynamics flexible fitting method

In recent years, cryo-electron microscopy (cryo-EM) has established itself as a key method in structural biology, permitting the structural characterization of large biomolecular complexes in various functional states. The data obtained through single-particle cryo-EM has recently seen a leap in resolution thanks to landmark advances in experimental and computational techniques, resulting in sub-nanometer resolution structures being obtained routinely. The remaining gap between these data and revealing the mechanisms of molecular function can be closed through hybrid modeling tools that incorporate known atomic structures into the cryo-EM data. One such tool, molecular dynamics flexible fitting (MDFF), uses molecular dynamics simulations to combine structures from X-ray crystallography with cryo-EM density maps to derive atomic models of large biomolecular complexes. The structures furnished by MDFF can be used subsequently in computational investigations aimed at revealing the dynamics of the complexes under study. In the present work, recent applications of MDFF are presented, including the interpretation of cryo-EM data of the ribosome at different stages of translation and the structure of a membrane-curvature-inducing photosynthetic complex.     

A simple and flexible Holm gatekeeping procedure

Major objectives of a clinical trial are commonly stated in a hierarchical order as primary and secondary. The parallel gatekeeping testing strategy provides an opportunity to assess secondary objectives when all or partial primary objectives are achieved. The current available gatekeeping procedures have different pros and cons so users either need to justify the assumption associated with some procedures or tolerate suboptimal power performance of other procedures. By applying the Holm test with a flexible alpha splitting technique, we propose a procedure which (1) is powerful for assessing the primary objectives, (2) can be used when no assumption can be made on the dependency structure of test statistics, and (3) has the full flexibility to allocate user-preferred alpha to assess the secondary objectives based on the number of primary objectives achieved. A real clinical trial example is used for illustration of the proposed procedure.     

Structural model of ligand-G protein-coupled receptor (GPCR) complex based on experimental double mutant cycle data: MT7 snake toxin bound to dimeric hM1 muscarinic receptor

The snake toxin MT7 is a potent and specific allosteric modulator of the human M1 muscarinic receptor (hM1). We previously characterized by mutagenesis experiments the functional determinants of the MT7-hM1 receptor interaction (Fruchart-Gaillard, C., Mourier, G., Marquer, C., Stura, E., Birdsall, N. J., and Servent, D. (2008) Mol. Pharmacol. 74, 1554–1563) and more recently collected evidence indicating that MT7 may bind to a dimeric form of hM1 (Marquer, C., Fruchart-Gaillard, C., Mourier, G., Grandjean, O., Girard, E., le Maire, M., Brown, S., and Servent, D. (2010) Biol. Cell 102, 409–420). To structurally characterize the MT7-hM1 complex, we adopted a strategy combining double mutant cycle experiments and molecular modeling calculations. First, thirty-three ligand-receptor proximities were identified from the analysis of sixty-one double mutant binding affinities. Several toxin residues that are more than 25 Å apart still contact the same residues on the receptor. As a consequence, attempts to satisfy all the restraints by docking the toxin onto a single receptor failed. The toxin was then positioned onto two receptors during five independent flexible docking simulations. The different possible ligand and receptor extracellular loop conformations were described by performing simulations in explicit solvent. All the docking calculations converged to the same conformation of the MT7-hM1 dimer complex, satisfying the experimental restraints and in which (i) the toxin interacts with the extracellular side of the receptor, (ii) the tips of MT7 loops II and III contact one hM1 protomer, whereas the tip of loop I binds to the other protomer, and (iii) the hM1 dimeric interface involves the transmembrane helices TM6 and TM7. These results structurally support the high affinity and selectivity of the MT7-hM1 interaction and highlight the atypical mode of interaction of this allosteric ligand on its G protein-coupled receptor target.     

A mechanically strong, flexible and conductive film based on bacterial cellulose/graphene nanocomposite

A highly flexible nanocomposite film of bacterial cellulose (BC) and graphene oxide (GO) with a layered structure was presented using the vacuum-assisted self-assembly technique. Microscopic and X-ray diffraction measurements demonstrated that the GO nanosheets were uniformly dispersed in the BC matrix. The interactions between BC and GO were studied by Fourier transformation infrared spectroscopy. Compared with pristine BC, the integration of 5 wt% GO resulted in 10% and 20% increase in Young's modulus and tensile strength of the composite film. The electrical conductivity of the composite film containing 1 wt% GO after in situ reduction showed a remarkable increase by 6 orders of magnitude compared with the insulated BC.