Advances in Causal Chain Development and Testing in Alcohol Research: Mediation, Suppression, Moderation, Mediated Moderation, and Moderated Mediation

Background:  While causal modeling is generally well known to alcohol researchers, several causal structures (including suppression, mediated moderation, and moderated mediation) are often poorly understood and seldom employed when investigators seek to model the complex mechanisms of behavior change, despite their widespread applicability to the field.
Methods:  This paper compares and contrasts five basic structures of causal modeling in the context of contemporary alcohol research and demonstrates how mechanisms of behavior change can be conceptualized and tested as parallel and serial sequences of these basic causal structures, forming causal chains.
Conclusion:  Recent methodological developments, while representing an important advancement for the field, fail to adequately address the complexities of alcohol dependence phenomena. A differentiation between frequently combined forms of these causal structures is proposed that would better address the needs of the field.     

Thalamic and cortical projections to middle suprasylvian cortex of cats: constancy and variation

 We investigated the constancy and variability in the numbers of thalamic and cortical neurons projecting to cat middle suprasylvian (MS) visual cortex. Retrograde pathway tracers were injected at a single anatomically and physiologically defined locus in MS cortex. Counts of labeled neurons showed that the visual thalamic projections to MS cortex consistently arose from a fixed set of nuclei in relatively constant proportions. In contrast, counts of cortical neurons revealed that transcortical inputs to MS cortex were much more variable. This differential variability may be linked to the developmental program, which affords greater influence of experiential factors on cortical pathway development than on thalamocortical pathway development. These results have implications for the development of models of cerebral connectivity that include measures of pathway variability. Received: 29 March 1996 / Accepted: 3 September 1996     

In Situ Thermal Denaturation of Proteins in Dunning AT-1 Prostate Cancer Cells: Implication for Hyperthermic Cell Injury

The in situ thermal protein denaturation and its correlation with direct hyperthermic cell injury in Dunning AT-1 prostate tumor cells were investigated in this study. The in situ thermal protein denaturation was studied using both Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The FTIR spectra at different temperatures show changes in protein secondary structure (from alpha helix to extended beta sheet) during in situ thermal protein denaturation within AT-1 cells. Calorimetric studies using DSC show that endothermic heat release is associated with the in situ thermal protein denaturation. Furthermore, both the secondary structure changes detected by FTIR and the calorimetric changes detected by DSC were quantified and the kinetics of the overall in situ thermal protein denaturation was derived under different heating conditions. The onset temperature where the overall in situ thermal protein denaturation is first detectable was found to be scanning rate dependent (approximately 41 degrees C at 2 degrees C min(-1) and approximately 44 degrees C at 5 degrees C min(-1)). The kinetics of the overall in situ thermal protein denaturation was derived from both DSC and FTIR measurements and was fit using kinetic and statistical models. The kinetic data determined by FTIR and DSC under the same heating conditions match well with each other. The activation energy of the overall in situ thermal protein denaturation is found to be strongly dependent on the temperature range considered (the activation energy ranges from approximately 110 kJ mol(-1) between 44 and 90 degrees C to approximately 750 kJ mol(-1) between 44 and 50 degrees C). However, its dependence on heating rate is negligible. Several denaturation peaks, including a dominant one between approximately 62 and 65 degrees C, are identifiable from both the DSC and the FTIR results. To investigate directly the relationship between thermally induced cell injury and the in situ thermal protein denaturation, both acute (propidium iodide dye exclusion, assessed 3-h postthermal treatment) and chronic (clonogenics, assessed 7-day postthermal treatment) cell injury were quantified using AT-1 cells prepared under the same conditions as for the DSC protein studies. Comparisons of the results from the cell injury studies and the DSC protein denaturation studies show that the overall in situ thermal protein denaturation correlates well with both the acute and the chronic cell injury, which suggests that overall in situ thermal protein denaturation is an important mechanism of direct hyperthermic cell injury in AT-1 cells at the macromolecular level.     

大学生网络成瘾影响因素分析

目的探讨大学生网络成瘾的原因。方法采用中文网络成瘾量表、自尊量表、孤独量表、大学生日常生活压力调查表、自编大学生网络使用行为调查问卷，对1450名大学生进行了调查，回收有效问卷1038份。结果对大学生网络成瘾的现状、网络使用特征及心理特征进行调查，建立大学生网络成瘾影响因素模型。结论①大学生网络成瘾呈轻度、重度两种水平，这两种水平总流行率达到14．84％；②网络使用时间、娱乐上网、交易上网、人际上网与网络成瘾存在着显著正相关关系；③自尊、孤独、大学生日常生活压力对网络成瘾有很好的预测作用；④网络成瘾是特定的个体心理特征与特定的网络使用行为、外部环境交互作用的结果。     

Remodeling of the ICF: A commentary

Since its publication in 2001 the International Classification of Functioning, Disability and Health (ICF) has attracted debate about the content and the model presented. After almost 20 years use, regular updating since 2008 and with the prospect of a new edition in 2020 there is increasing interest in the ICF as a tool to meet contemporary information requirements. Information on functioning is important across not only health systems, but all areas where change in functioning is important: education, employment, and social welfare for example. This commentary responds to the issues raised in a commentary by Mitra & Shakespeare in 2019 and supports review of the ICF in the current context by informing users and providers of data on human functioning how they might engage in the maintenance, updating, and modernisation of the ICF.     

针灸治疗胃肠疾病的实验研究文献计量分析与数据挖掘

目的：统计分析2016—2020年期间发表的针灸治疗胃肠疾病的实验研究文献,总结归纳针灸治疗胃肠道疾病的主要研究方向与进展。方法：检索国家知识基础设施数据库（CNKI）、中国学术期刊数据库（CSPD）、中文科技期刊数据库（CCD）、Pubmed及Web of Science数据库,根据纳入与排除标准筛选针灸治疗胃肠疾病的实验研究文献,并对结果进行计量统计分析。结果：近5年来针灸治疗功能性胃肠疾病的实验研究以肠易激综合征与功能性消化不良为主,器质性胃肠病则是以溃疡性结肠炎为主。电针和灸法是针灸治疗胃肠疾病的主要方法,功能性胃肠病以电针干预为主,器质性胃肠病以灸法为主。足三里、天枢、上巨虚、中脘是针灸治疗胃肠疾病的主要穴位。功能性胃肠疾病的针灸实验研究侧重于胃肠动力、内脏高敏感、情绪相关机制,器质性胃肠疾病的针灸实验研究侧重于炎症与免疫相关机制。结论：近5年针灸治疗功能性胃肠疾病实验以电针干预为主,侧重于胃肠动力、内脏高敏感、情绪相关机制研究;器质性胃肠病的针灸实验研究以灸法为主,侧重于炎症与免疫相关机制。     

Noninvasive loading of the rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periostal pressure

Adaptive changes in bone modeling in response to noninvasive, cyclic axial loading of the rat ulna were compared with those using 4-point bending of the tibia. Twenty cycles daily of 4-point bending for 10 days were applied to rat tibiae through loading points 23 and 11 mm apart. Control bones received nonbending loads through loading points 11 mm apart. As woven bone was produced in both situations, any strain-related response was confounded by the response to direct periosteal pressure. Four-point bending is not, therefore, an ideal mode of loading for the investigation of strain-related adaptive modeling. The ulna's adaptive response to daily axial loading over 9 days was investigated in 30 rats. Groups 1–3 were loaded for 1200 cycles: Group 1 at 10 Hz and 20 N, Group 2 at 10 Hz and 15 N, and Group 3 at 20 Hz and 15 N. Groups 4 and 5 received 12,000 cycles of 20 N and 15 N at 10 Hz. Groups 1 and 4 showed a similar amount of new bone formation. Group 4 showed the same pattern of response but in reduced amount. The responses in Groups 2 and 3 were either small or absent. Strains were measured with single-element, miniature strain gauges bonded around the circumference of dissected bones. The 20 N loading induced peak strains of 3500–4500 strain. The width of the periosteal new bone response was proportional to the longitudinal strain at each point around the bone's circumference. It appears that when a bone is loaded in a normal strain distribution, an osteogenic response occurs when peak physiological strains are exceeded. In this situation the amount of new bone formed at each location is proportional to the local surface strain. Cycle numbers between 1200 and 12,000, and cycle frequencies between 10 and 20 Hz have no effect on the bone's adaptive response.     

生物合成调控的青霉素发酵数学模型与过程优化

青霉素生物合成受溶解氧、溶解二氧化碳、pH、氨氮、碳源(特别是葡萄糖)等的调控，这些调控反应的产生不仅与基础培养基配方有关，更受发酵过程通气、搅拌条件及补料方案的影响。为此，笔者通过把握发酵过程中产生菌生长和青霉素生物合成代谢流的元素平衡、能量平衡以及传递与反应速度平衡的方法，结合生产经验和数据资料，建立了一种能够模拟青霉素发酵过程工艺学参数和经济学参数变化的数学模型。应用这一模型，在充分考虑生物合成代谢调控的基础上，对青霉素发酵过程进行优化，即通过补水维持上述平衡，避免因环境条件、初始条件和约束条件的变化及人为的失误造成的过程波动，使生产不断趋向最优状态。模拟运行表明，这种优化可显著提高发酵生产的经济效益。     

Influence of iron oxide nanoparticles (Fe3O4) on erythrocyte photohemolysis via photofrin and Rose Bengal sensitization

BackgroundIron oxide (Fe₃O₄) nanoparticles (IO-NP) were recently employed in medical applications as a diagnostic tool and drug carrier. Photofrin (PF) is a photosensitizer that clinically is used in Photodynamic therapy (PDT).Study designThe photosensitivity of PF and Rose Bengal (RB) mixed with (IO-NP) on red blood cells (RBCs) lysis was investigated. Second, Photohemolysis for post-irradiation (delayed) and during irradiation (continuous) with PF, RB and IO-NP combinations at different concentrations was investigated. Third, the photohemolysis rate, relative lysis steepness and power-concentration dependant parameter were evaluated by modeling and fitting the data using Gompertz function and power law.MethodsRBCs were isolated from healthy male human volunteer. Washed cells (7.86 × 10⁶ cells/mm³) were incubated with PF only or with IO-NP for 45 min at 37 °C then irradiated to a range of temperatures (4–41 °C). CPH results were recorded and evaluated using Gompertz function.ResultsThe relative steepness of the photohemolysis curves was approximately independent on light dose for delayed irradiation. The presence of IO-NP increases the rupturing time for 50% of the RBCs. Photohemolysis rate for delayed irradiation using the power law, led to 1.7 and 2.3 power dependence, respectively, for PF only and PF mixed with IO-NP. The power dependence of continuous irradiation measurements showed inverse proportionality for different concentrations of IO-NP combined with 2 μg/ml PF concentration and 1.5 μg/ml for RB concentration.ConclusionPhotosensitization of RBC with PF or RB mixed with IO-NP inhibited rupturing erythrocyte membrane and therefore a consideration should be taken against their combination in clinical applications.     

NONLINEAR INTERDEPENDENCE IN NEURAL SYSTEMS: MOTIVATION,THEORY, AND RELEVANCE

In this article, we motivate models of medium to large-scale neural activity that place an emphasis on the modular nature of neocortical organization and discuss the occurrence of nonlinear interdependence in such models. On the basis of their functional, anatomical, and physiological properties, it is argued that cortical columns may be treated as the basic dynamical modules of cortical systems. Coupling between these columns is introduced to represent sparse long-range cortical connectivity. Thus, neocortical activity can be modeled as an array of weakly coupled dynamical subsystems. The behavior of such systems is represented by dynamical attractors, which may be fixed point, limit cycle, or chaotic in nature. If all the subsystems are perfectly identical, then the state of identical chaotic synchronization is a possible attractor for the array. Following the introduction of parameter variation across the array, such a state is not possible, although two other important nonlinear interdependences--generalized and phase synchronized--are possible. We suggest that an understanding of nonlinear interdependence may assist advances in models of neural activity and neuroscience time series analysis.