Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Etiology in a taxonomy of illnesses

According to what Robert Koch termed the etiological standpoint, illnesses are best understood and controlled by focusing on their causes, including in their definitions and, thus, in the construction of their taxonomies. In some ways flawed, this standpoint has been misunderstood and misapplied. A taxonomy based solely on etiology was an unrealistic dream in the context of 'the bacteriological revolution', and it also is unrealistic in the present context of 'the genetic revolution.' We argue that the illnesses in a taxonomy of them are in some cases best defined directly in terms of their respective somatic anomalies, in some others indirectly by the unique and universal etiology of that anomaly (left unspecified) in a 'deeper' somatic anomaly, and in yet others as a combination of these; and when the somatic anomaly for direct definition remains unknown, it is to be defined indirectly by the clinical syndrome that is its patient-relevant manifestation, possibly in conjunction with a somatic cause. We note, also, that these taxonomic issues have no material bearing on epidemiologists' etiologic research for the knowledge base of community-level preventive medicine.

Where the land is greener: Case studies and analysis of soil and water conservation initiatives worldwide

‘where the land is greener’ looks at soil and water conservation from a global perspective. In total, 42 soil and water conservation technologies and 28 approaches are described – each fully illustrated with photographs, graphs and line drawings – as applied in case studies in more than 20 countries around the world. This unique presentation of case studies draws on WOCAT’s extensive database, gathered in over 12 years of field experience. The book is intended as a prototype for national and regional compilations of sustainable land management practices a practical – instrument for making field knowledge available to decision makers. Various land use categories are covered, from crop farming to grazing and forestry. The technologies presented range from terrace-building to agroforestry systems; from rehabilitation of common pastures to conservation agriculture; from Vermiculture to water harvesting. Several of these technologies are already well-established successes – others are innovative, relatively unknown, but full of promise. Descriptions of the various technologies are complemented by studies of the ‘approaches’ that have underpinned their development and dissemination. Some of these approaches were developed specifically for individual projects; others developed and spread spontaneously in fascinating processes that offer a new perspective for development policy. In addition to the case studies, the book includes two analytical sections on the technologies and approaches under study. By identifying common elements of success, these analyses offer hope for productive conservation efforts at the local level with simultaneous global environmental benefits. Policy pointers for decision makers and donors offer a new impetus for further investment – to make the land greener.

Teaching and assessment of implant dentistry in undergraduate and postgraduate education: a European consensus

This paper constitutes a summary of the consensus documents agreed at the First European Workshop on Implant Dentistry University Education held in Prague on 19-22 June 2008. Implant dentistry is becoming increasingly important treatment alternative for the restoration of missing teeth, as patients expectations and demands increase. Furthermore, implant related complications such as peri-implantitis are presenting more frequently in the dental surgery. This consensus paper recommends that implant dentistry should be an integral part of the undergraduate curriculum. Whilst few schools will achieve student competence in the surgical placement of implants this should not preclude the inclusion of the fundamental principles of implant dentistry in the undergraduate curriculum such as the evidence base for their use, indications and contraindications and treatment of the complications that may arise. The consensus paper sets out the rationale for the introduction of implant dentistry in the dental curriculum and the knowledge base for an undergraduate programme in the subject. It lists the competencies that might be sought without expectations of surgical placement of implants at this stage and the assessment methods that might be employed. The paper also addresses the competencies and educational pathways for postgraduate education in implant dentistry.

Critical appraisal of meta-analyses: an introductory guide for the practicing surgeon

ABSTRACT: Meta-analyses are an essential tool of clinical research. Meta-analyses of individual randomized controlled trials frequently constitute the highest possible level of scientific evidence for a given research question and allow surgeons to rapidly gain a comprehensive understanding of an important clinical issue. Moreover, meta-analyses often serve as cornerstones for evidence-based surgery, treatment guidelines, and knowledge transfer. Given the importance of meta-analyses to the medical (and surgical) knowledge base, it is of cardinal importance that surgeons have a basic grasp of the principles that guide a high-quality meta-analysis, and be able to weigh objectively the advantages and potential pitfalls of this clinical research tool. Unfortunately, surgeons are often ill-prepared to successfully conduct, critically appraise, and correctly interpret meta-analyses. The objective of this educational review is to provide surgeons with a brief introductory overview of the knowledge and skills required for understanding and critically appraising surgical meta-analyses as well as assessing their implications for their own surgical practice.

Organisational and methodical aspects of drug and addiction prevention among young people. Developments in the Ukraine, in Germany, Spain and Russia (Project Description)

From october 2000 to march 2003 the project has been coordinated by the institute of social work and welfare studies of the TU Dresden and financed by the European Commission (INCO-COPERNICUS-Programme). It was an international cooperation between the TU Dresden (Germany), the University of Internal Affairs and the National Technical University in Kharkiv (Ukraine), the research institute AREA in Valenciá (Spain) and the Belgorod Juridical Institute of the Ministry of Internal Affairs (Russia) which was established for improving the knowledge base of drug prevention activities by the East European partners. The overall aim of the project was the analysis and elaboration of approaches to drug and addiction prevention. Under consideration of the specific conditions within the East-European countries this work should contribute to the development of pluralistic approaches towards health promotion which are embedded into an intercultural, European horizon.

Making research works visible and stimulating a research milieu in the field of social work - The European Resource Centre for Social Work Research (CERTS)

The project to create a European Resource Centre for Social Work Research (CERTS) has been agreed in December 2001 by the General Research Board of the European Commission within the framework programme 'Accompanying Measures for the improving the Human research potential and the Socio Economic Knowledge Base'.

Everyday Sexuality and Social Work: Locating Sexuality in Professional Practice and Education

Social work has seen increased intellectual interest in sexuality. However, little attention has been paid to the relevance of everyday sexuality for professional practice or how this might be integrated within existing social work curricula. This paper proposes that knowledge about everyday sexuality is vital to social workers as they deal with a variety of clients faced with the increasing complexities brought about by late-modernity. Additionally, it is argued that this knowledge base is congruent with the ethical and political dimensions of the profession. The PLISSIT model is presented as a possible pedagogical framework for social work education in this area.

Professionalism and Information Technology: Positioning and Mediation

The starting point of this paper is the assumption that - on the one hand - information technology (IT) is increasingly shaping the professional knowledge base and on the other the relation between organisation and profession. IT is changing the role, responsibilities and practices of social workers and therefore it is important to deal with the impact of IT on social work (representative for many: Harlow and Webb 2003; Burton and van den Broek 2008). Hence, the general aim of this paper is to stimulate a basic discussion on “IT application in social work“, or rather, in a more general way, on „technology and professions“. Secondly, it is about an analytical differentiation of the process of informatisation, respectively formalisation. Thirdly we want to discuss the assumption and overall combination of efficiency, effectiveness and IT. Therefore this paper is arranged as follows: After some opening remarks (chapter 1) we outline case management systems as research object (2). Further on, we confront the approach of reflexive professionalism (3) with the process of formalization (4). Subsequently, we touch on the debate of “technologies of care” (5) and conclude with some short remarks on a research program (6).

Ontologies and Methods for Interoperability of Engineering Analysis Models (EAMS) in an E-Design Environment

ABSTRACT ONTOLOGIES AND METHODS FOR INTEROPERABILITY OF ENGINEERING ANALYSIS MODELS (EAMS) IN AN E-DESIGN ENVIRONMENT SEPTEMBER 2007 NEELIMA KANURI, B.S., BIRLA INSTITUTE OF TECHNOLOGY AND SCIENCES PILANI INDIA M.S., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Ian Grosse Interoperability is the ability of two or more systems to exchange and reuse information efficiently. This thesis presents new techniques for interoperating engineering tools using ontologies as the basis for representing, visualizing, reasoning about, and securely exchanging abstract engineering knowledge between software systems. The specific engineering domain that is the primary focus of this report is the modeling knowledge associated with the development of engineering analysis models (EAMs). This abstract modeling knowledge has been used to support integration of analysis and optimization tools in iSIGHT FD , a commercial engineering environment. ANSYS , a commercial FEA tool, has been wrapped as an analysis service available inside of iSIGHT-FD. Engineering analysis modeling (EAM) ontology has been developed and instantiated to form a knowledge base for representing analysis modeling knowledge. The instances of the knowledge base are the analysis models of real world applications. To illustrate how abstract modeling knowledge can be exploited for useful purposes, a cantilever I-Beam design optimization problem has been used as a test bed proof-of-concept application. Two distinct finite element models of the I-beam are available to analyze a given beam design- a beam-element finite element model with potentially lower accuracy but significantly reduced computational costs and a high fidelity, high cost, shell-element finite element model. The goal is to obtain an optimized I-beam design at minimum computational expense. An intelligent KB tool was developed and implemented in FiPER . This tool reasons about the modeling knowledge to intelligently shift between the beam and the shell element models during an optimization process to select the best analysis model for a given optimization design state. In addition to improved interoperability and design optimization, methods are developed and presented that demonstrate the ability to operate on ontological knowledge bases to perform important engineering tasks. One such method is the automatic technical report generation method which converts the modeling knowledge associated with an analysis model to a flat technical report. The second method is a secure knowledge sharing method which allocates permissions to portions of knowledge to control knowledge access and sharing. Both the methods acting together enable recipient specific fine grain controlled knowledge viewing and sharing in an engineering workflow integration environment, such as iSIGHT-FD. These methods together play a very efficient role in reducing the large scale inefficiencies existing in current product design and development cycles due to poor knowledge sharing and reuse between people and software engineering tools. This work is a significant advance in both understanding and application of integration of knowledge in a distributed engineering design framework.

Semantic Methods for Intelligent Distributed Design Environments

Continuous advancements in technology have led to increasingly comprehensive and distributed product development processes while in pursuit of improved products at reduced costs. Information associated with these products is ever changing, and structured frameworks have become integral to managing such fluid information. Ontologies and the Semantic Web have emerged as key alternatives for capturing product knowledge in both a human-readable and computable manner. The primary and conclusive focus of this research is to characterize relationships formed within methodically developed distributed design knowledge frameworks to ultimately provide a pervasive real-time awareness in distributed design processes. Utilizing formal logics in the form of the Semantic Web’s OWL and SWRL, causal relationships are expressed to guide and facilitate knowledge acquisition as well as identify contradictions between knowledge in a knowledge base. To improve the efficiency during both the development and operational phases of these “intelligent” frameworks, a semantic relatedness algorithm is designed specifically to identify and rank underlying relationships within product development processes. After reviewing several semantic relatedness measures, three techniques, including a novel meronomic technique, are combined to create AIERO, the Algorithm for Identifying Engineering Relationships in Ontologies. In determining its applicability and accuracy, AIERO was applied to three separate, independently developed ontologies. The results indicate AIERO is capable of consistently returning relatedness values one would intuitively expect. To assess the effectiveness of AIERO in exposing underlying causal relationships across product development platforms, a case study involving the development of an industry-inspired printed circuit board (PCB) is presented. After instantiating the PCB knowledge base and developing an initial set of rules, FIDOE, the Framework for Intelligent Distributed Ontologies in Engineering, was employed to identify additional causal relationships through extensional relatedness measurements. In a conclusive PCB redesign, the resulting “intelligent” framework demonstrates its ability to pass values between instances, identify inconsistencies amongst instantiated knowledge, and identify conflicting values within product development frameworks. The results highlight how the introduced semantic methods can enhance the current knowledge acquisition, knowledge management, and knowledge validation capabilities of traditional knowledge bases.

Analysis of Variation in Clubfoot Candidate Genes

Isolated clubfoot, a common birth defect occurring in more than 135,000 livebirths worldwide each year, is associated with significant health care and financial burdens. Clubfoot is defined by forefoot adduction, hindfoot varus, midfoot cavus and hindfoot equinus. Isolated clubfoot, which is the focus of these studies, is distinct from syndromic clubfoot because there are no other associated malformations. Population, family, twin and segregation analysis studies provide evidence that genetic and environmental factors play an etiologic role in isolated clubfoot. The studies described in this thesis were performed to define the role of genetic variation in isolated clubfoot. Interrogation of a deletion region associated with syndromic clubfoot, suggested that CASP8 and CASP10, two apoptotic genes, play a role in isolated clubfoot. To explore the role of apoptotic genes in clubfoot, SNPs spanning genes involved in the apoptotic pathway in the six chromosomal deletion regions, and limb patterning genes, HOXD and HOXA, were interrogated. SNPs in mitochondrial mediated apoptotic genes and several SNPs in HOXA and HOXD genes were modestly associated with clubfoot with the most significant SNP, rs3801776, located in the basal promoter of HOXA9. Several significant associations were found with SNPs in NFAT2 and TNIP2. Significant gene interactions were detected between SNPs in HOX and apoptotic genes. These findings suggest a model for clubfoot in which variation in one gene is not sufficient to cause the malformation but requires variation several genes to perturb protein expression sufficiently to alter muscle and foot development. These results significantly impact our knowledge base by delineating underlying mechanisms causing clubfoot.