Research in Training Clinics and Practice Research Networks: A Route to the Integration of Science and Practice

The present commentary encourages the development of research infrastructures within the training clinics of clinical psychology programs, the use of such infrastructures for creating a true integration of science and practice in the earliest days of graduate student education, and the formation of collaborative practice research networks among clinics and across other mental health agencies. Such developments may contribute to more rapid creation of ways of integrating science and practice and to methods for creating large-scale, scientifically rigorous, and clinically meaningful research to answer the most pressing questions that our profession faces.     

How psychotherapy integration can complement the scientist-practitioner model

This article aims to integrate the two separate bodies of literature in Psychotherapy Integration (PI) and the Scientist-Practitioner (S-P) model. Based on an examination and synthesis of the main ideas from the two fields, it illustrates that, although developed separately, these movements are compatible and they complement each other. After describing the historical, empirical, and conceptual relationship of the two movements, the implications of this relationship for psychotherapy are outlined and recommendations are offered. PI is conceptualized as a key ingredient in the optimal expression of the S-P model, which can address several difficulties in the actualization of the model.     

Addressing the challenges of transforming laboratory advances into Alzheimer's Disease treatments

This essay addresses the challenges of clinical trials to develop treatments for Alzheimer’s Disease (AD). The issues covered are enrolling subjects, defining clinically meaningful endpoints, and making the claim that a drug slows the progression of the disease. The perspective to address these challenges is that dementia research should embrace a biopsychosocial model for drug development. In this model, the patient and caregiver are seen as interrelated subjects of both treatment and research and outcome measures reflect biomarkers of the disease, the functional morbidity of AD and the distress of caregiving.     

RNA meets chromatin

In the universe of science, two worlds have recently collided-those of RNA and chromatin. The intersection of these two fields has been impending, but evidence for such a meaningful collision has only recently become apparent. In this review, we discuss the implications for noncoding RNAs and the formation of specialized chromatin domains in various epigenetic processes as diverse as dosage compensation, RNA interference-mediated heterochromatin assembly and gene silencing, and programmed DNA elimination. While mechanistic details as to how the RNA and chromatin worlds connect remain unclear, intriguing parallels exist in the overall design and machinery used in model organisms from all eukaryotic kingdoms. The role of potential RNA-binding chromatin-associated proteins will be discussed as one possible link between RNA and chromatin.     

The sixth international RASopathies symposium: Precision medicine—From promise to practice

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life‐limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion.     

Integrating science and practice: Reclaiming the science in practice

This article is intended to be somewhat provocative, stimulating discussion in our efforts to better integrate science and practice. Three major areas of divisiveness between science and practice are posited-understanding of practitioners' approach to practice, definition of scholarship, and the role of theory and diagnosis in practice. Some general principles are offered that may further our thinking about integration of the applications of science in the practice of psychology and the participation of practitioners in science: (a) all practitioners do evidence-based practice; (b) scholarship has many forms, each of which provides an important piece of the puzzle of advancing knowledge; and (c) "eclectic" is a theoretically and practically meaningful term.     

Effects of antimicrobial drugs on human neutrophil-microbe interactions

Antimicrobial drugs may influence neutrophil-microbe interactions in several ways, and, conversely, neutrophils may interfere with the action(s) of antimicrobial drugs. Here, evidence for the existence of such effects is evaluated and attention drawn to the problems of in vitro experimentation in this area. The review is restricted to those studies that used human neutrophils, clinically achievable drug concentrations, and were well designed. Even so, it is noted that little attempt has been made to investigate underlying mechanisms. The effects of drugs on microbes, which influence neutrophil-microbe interactions, such as concentration and the post-antibiotic effect, are considered. The penetration of antimicrobial drugs into neutrophils and subsequent intracellular activity is discussed and contrasted with observations obtained using macrophages. Overall, neutrophil-microbe interactions are complex and difficult to dissect, and carefully designed experiments using closely defined conditions are required if meaningful results are to be obtained.     

Depression among Latinos in the United States: a meta-analytic review

The authors conducted a meta-analytic review to assess the prevalence of major depressive disorder and depressive symptoms among Latinos compared with non-Latino Whites in the United States using community-based data. Random-effects estimates were calculated for 8 studies meeting inclusion criteria that reported lifetime prevalence of major depressive disorder (combined N = 76,270) and for 23 studies meeting inclusion criteria that reported current prevalence of depressive symptoms (combined N = 38,997). Findings did not indicate a group difference in lifetime prevalence of major depressive disorder (odds ratio = 0.89, 95% confidence interval = 0.72, 1.10). Latinos reported more depressive symptoms than non-Latino Whites (standardized mean difference = 0.19, 95% confidence interval = 0.12, 0.25); however, this effect was small and does not appear to suggest a clinically meaningful preponderance of depressive symptoms among Latinos. Findings are examined in the context of theories on vulnerability and resilience, and recommendations for future research are discussed.     

知识模式转换在医学科技创新中的作用

医学科技创新是医院赖以生存与发展的动力,医学科技创新的过程也是医学知识模式不断转换的过程,本文从知识模式转换的视角,探讨知识管理对医学科技创新的意义与作用     

Numerical model to predict the longterm mechanical stability of cementless orthopaedic implants

The objective of this research was to develop a purely biomechanical model, intended to predict the long-term secondary stability of the implant starting from the biomechanical stability immediately after the operation. A continuous rulebased adaptation scheme was formulated as a dynamic system, and the work verified if such a model produced unique and clinically meaningful solutions. It also investigated whether this continuous model provided results comparable with those of a simpler, discrete-states model used in a previous study. The proposed model showed stable convergence behaviour with all investigated initial conditions, with oscillatory behaviour limited to the first steps of the simulation. The results obtained with the wide range of initial conditions support the hypothesis of the existence and uniqueness of the solution for all initial conditions. The differences between the continuous model and the simpler and more efficient finite-states model were found to be extremely modest (less than 4% over the predicted bonded area). Because of these minimal differences, the use of the much faster finite-states model is recommended to investigate asymptotic conditions, and the continuous model described should be used to investigate the evolution over time of the adaptive process.     

视觉假体的发展与研究

目的:介绍国内外主要视觉假体研究小组的研究进展,讨论了视觉假体研究的重点与难点。方法:回顾并分析了植入在视皮层、视神经、视网膜的三种视觉假体的功能特点和其优缺点。结果:视觉假体在未来发展的最大障碍已不再是假体的设计加工和手术技术,而是如何在假体与大脑之间进行有效信息传递。结论:目前视觉假体仍未能满足失明患者日常需要,开发具有完整功能的视觉假体有着广阔的空间。     

Malignant astrocytic glioma: genetics, biology, and paths to treatment

Malignant astrocytic gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, resistance to traditional and newer targeted therapeutic approaches, destruction of normal brain tissue, and certain death. The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized our understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma. This progress is fueling new opportunities for understanding the fundamental basis for development of this devastating disease and also novel therapies that, for the first time, portend meaningful clinical responses.     

恶性黑色素瘤的免疫组织化学鉴别诊断

以Ｓ－１００、Ｖｉｍｅｎｔｉｎ、ＨＭＢ４５、Ｋｅｒａｔｉｎ、ＥＭＡ、ＬＣＡ抗体，ＳＰ法对原病理诊断或疑诊的３５例恶性黑色素瘤（ＭＭ）进行染色。结果１０例典型的少色素性ＭＭ均呈Ｓ－１００、Ｖｉｍｅｎｔｉｎ和ＨＭＢ４５阳性，符合原ＭＭ诊断。原病理诊断１９例和疑诊６例共２５例无色素性恶性黑色素瘤（ＡＭＭ）中，２１例同时呈Ｓ－１００、ｖｉｍｅｎｔｉｎ和ＨＭＢ４５阳性，故确诊为ＡＭＭ；４例Ｓ－１００和ＨＭＢ４５阴性肿瘤中，３例为Ｋｅｒａｔｉｎ阳性、ＥＭＡ弱阳性，１例为ＬＣＡ和Ｖｉｍｅｎｔｉｎ阳性，证实不是ＭＭ而是癌和淋巴瘤。结果表明，Ｓ－１００和ＨＭＢ４５是ＭＭ诊断性标志物，后者具有特异性。     

The SHEL model: a useful tool for analyzing and teaching the contribution of Human Factors to medical error.

Recent reports on the problem of medical error pointed to a discipline that has been until recently, largely disregarded by the medical profession. The interdisciplinary science of Human Factors, the reports argue, provides a pragmatic framework for analyzing and assessing risk and reducing error in health care. The argument for applying Human Factors analysis to health care is increasingly accepted, and the application of Human Factors systems models for understanding medical error in particular have proved to be especially illuminating. The authors present a conceptual model of Human Factors--the SHEL model (named after the initial letters of its components' names, Software, Hardware, Environment, and Liveware)--that has been used in investigations of error in aviation. The authors use this simple model to examine and elucidate the Human Factors issues in a specific real-life example of medical error. The SHEL model is particularly useful in examining Human Factors issues in microsystems in health care such as the emergency room or the operating theatre; it argues that mismatches at the interface between the components in these health care microsystems are often conducive to medical errors. The authors propose that the SHEL model may have some unexploited potential in analyzing error and in training medical professionals about the science of Human Factors and its application to medical error. Empirical studies are needed, however, to ascertain the optimal amount of training needed to make clinically significant reductions in the occurrence of medical error.     

Dendritic Cell Therapy of High-Grade Gliomas

The prognosis of patients with malignant glioma is poor in spite of multimodal treatment approaches consisting of neurosurgery, radiochemotherapy and maintenance chemotherapy. Among innovative treatment strategies like targeted therapy, antiangiogenesis and gene therapy approaches, immunotherapy emerges as a meaningful and feasible treatment approach for inducing long-term survival in at least a subpopulation of these patients. Setting up immunotherapy for an inherent immunosuppressive tumor located in an immune-privileged environment requires integration of a lot of scientific input and knowledge of both tumor immunology and neuro-oncology. The field of immunotherapy is moving into the direction of active specific immunotherapy using autologous dendritic cells (DCs) as vehicle for immunization. In the translational research program of the authors, the whole cascade from bench to bed to bench of active specific immunotherapy for malignant glioma is covered, including proof of principle experiments to demonstrate immunogenicity of patient-derived mature DCs loaded with autologous tumor lysate, preclinical in vivo experiments in a murine orthotopic glioma model, early phase I/II clinical trials for relapsing patients, a phase II trial for patients with newly diagnosed glioblastoma (GBM) for whom immunotherapy is integrated in the current multimodal treatment, and laboratory analyses of patient samples. The strategies and results of this program are discussed in the light of the internationally available scientific literature in this fast-moving field of basic science and translational clinical research.     

Early intervention for low birth weight,preterm infants: the role of negative emotionality in the specification of effects

This study examined the relation of negative emotionality in infancy to child social and cognitive developmental outcomes among low birth weight (LBW) preterm infants participating in the Infant Health and Development Program (IHDP), a comprehensive compensatory education intervention beginning in infancy and lasting through age 3 years. In this analysis, intervention effects at age 36 months on maternal report of child behavior as assessed by the Child Behavior Checklist externalizing and internalizing scales and on intelligence as measured by the Stanford-Binet scale were largest among children characterized by higher levels of negative emotionality in infancy. Findings indicate that for LBW preterm infants characterized by negative emotionality at age 12 months the intervention was associated with a twofold decrease in the occurrence of clinically meaningful levels of behavior problems at age 3 years and a fourfold decrease in the occurrence of a high-risk profile in which both internalizing and externalizing scores are in the clinically meaningful range. The intervention was also associated with a fivefold decrease in the occurrence of IQ < or = 75 at age 3 years among children with higher levels of negative emotionality and heavier LBW (2001-2500 g). However, specific aspects of temperamental difficulty such as fearfulness and anger were related to internalizing and externalizing, respectively, in both the intervention and control groups. Findings are consistent with research linking negative emotionality in infancy with social and cognitive developmental outcomes in early childhood among normal birth weight infants. Results suggest the need for further attention to child temperament in early intervention research.     

中国幼儿智力量表(CISYC)短、中期重测信度的研究

中国幼儿智力量表(ＣＩＳＹＣ)是“八五”期间由我国自行研制的一个用于评价3至7岁儿童智力水平的测验[1-3]。信度、效度研究结果表明,该量表具有较好的分半信度、同时效度和区分效度,重测信度(校正后)达到08以上水平。有关心理测验稳定性的研究认为,两次测验的时间间隔的...     

Latent structure of the Wisconsin Card Sorting Test in a clinical sample.

The aims of this study were to: (a) examine the consistency of the published Wisconsin Card Sorting Test (WCST) factor structures; (b) determine the factor structure of the WCST in a large, heterogeneous sample; and (c) compare the WCST factor analytically with other neuropsychological procedures. Two WCST factors (concept formation/perseveration and Failure-to-Maintain-Set [FMS]) were consistently reported in the literature. Our analysis of data from 473 clinical cases replicated the two factors previously reported and revealed a third on which nonperseverative errors (NPE) was the sole salient variable. This pattern was maintained in three of four diagnostically distinct subgroups. These factors are potentially clinically meaningful, with each seeming to reflect one of three qualitatively different performance styles. In the construct validation factor analysis, WCST scores loaded independently of other neuropsychological variables, indicating that the WCST contributes uniquely to neuropsychological evaluation. Nevertheless, despite the rational interpretation of the factors, the cognitive processes underlying WCST performance remain poorly understood. Future directions for the application of these factor analytic findings are discussed.     

Scientific rationale behind the development and approval of biosimilar infliximab (CT-P13) in Europe

Biosimilars are drugs developed to be highly similar to their originator biologic (or ‘reference medicinal product’) with no clinically meaningful differences in purity, efficacy or safety. Production of biologics and biosimilars is highly complex and sensitive, with any change in manufacturing process having a potential impact on efficacy and safety. This review provides an overview of the manufacturing process for these drugs and considers the implications of any process changes. The scientific rationale underlying the regulatory comparability exercise for process-changed reference medicinal products and biosimilars is also discussed, as is the issue of ‘switchability’ from a reference medicinal product to its biosimilar. CT-P13 (Remsima^®, Inflectra^®), a biosimilar of infliximab, is used as a case study to discuss these issues.