Protocol for a systematic review of guidelines for rigour in the design, conduct and analysis of biomedical experiments involving laboratory animals

Objective: Within the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclinical biomedical research. Search strategy: PubMed, Embase and Web of Science will be searched systematically to identify guidelines published in English language in peer-reviewed journals before January 2018 (box 1). All articles or systematic reviews in English language that describe or review guidelines on the internal validity and reproducibility of animal studies will be included. Google search for guidelines published on the websites of major funders and professional organisations can be found in (Box 2). Screening and annotation: Unique references will be screened in two phases: screening for eligibility based on title and abstract, followed by screening for definitive inclusion based on full text. Screening will be performed in SyRF (http://syrf.org.uk). Each reference will be randomly presented to two independent reviewers. Disagreements between reviewers will be resolved by additional screening of the reference by a third, senior researcher. Data management and reporting: All data, including extracted text and guidelines, will be stored in the SyRF platform. Elements of the included guidelines will be identified using a standardized extraction form. Reporting will follow the PRISMA guidelines as far as applicable

Microstructure and wear behaviour of high alloyed hot-work tool steels 1.2343 and 1.2367 under thermo-mechanical loading

Tools and their maintenance costs in hot forging processes account for a considerable proportion of the total components' costs. Forging tools undergo extreme heating and subsequent cooling during the forging process and between the forging cycles, respectively. This cyclic heating and cooling of the tool surfaces leads to local changes in the tool microstructure which result in hardening or softening of the material in different regions of the tool and consequently influence the tool strength. Temperature in the tool areas experiencing high thermo-mechanical loadings can exceed the austenitic temperature. Hence, a strong cooling, for example by spraying or lubrication, can lead to formation of a martensitic layer in the boundary zone of the tool. Due to its higher hardness, martensitic layer has greater resistance to wear as compared to the basic or tempered materials. In the scope of this paper, the austenitisation behaviours of two high alloyed hot-work tool steels, 1.2343 and 1.2367, have been characterized by means of dilatometer tests to obtain time-temperature-austenitisation (TTA) diagrams for specimen under thermo-mechanical loads. Moreover, continuous-cooling-transformation (CCT) diagrams were recorded. Metallographic investigations were carried out to gather a detailed understanding of the microstructure behaviour and its resulting hardness. With the results of this works, it is aimed to gather a detailed and accurate insight into the arising hardening and softening effects. This would eventually lead to an optimisation of the numerical modelling for tool wear prediction

NLL soft and Coulomb resummation for squark and gluino production at the LHC

We present predictions of the total cross sections for pair production of squarks and gluinos at the LHC, including the stop-antistop production process. Our calculation supplements full fixed-order NLO predictions with resummation of threshold logarithms and Coulomb singularities at next-to-leading logarithmic (NLL) accuracy, including bound-state effects. The numerical effect of higher-order Coulomb terms can be as big or larger than that of soft-gluon corrections. For a selection of benchmark points accessible with data from the 2010-2012 LHC runs, resummation leads to an enhancement of the total inclusive squark and gluino production cross section in the 15-30 % range. For individual production processes of gluinos, the corrections can be much larger. The theoretical uncertainty in the prediction of the hard-scattering cross sections is typically reduced to the 10 % level.Comment: 45 pages, 16 Figures, LaTex. v2: published version. Grids with numerical results for the NLL cross sections for squark and gluino production at the 7/8 TeV LHC are included in the submission and are also available at http://omnibus.uni-freiburg.de/~cs1010/susy.htm

Analytic frameworks for assessing dialogic argumentation in online learning environments

Over the last decade, researchers have developed sophisticated online learning environments to support students engaging in argumentation. This review first considers the range of functionalities incorporated within these online environments. The review then presents five categories of analytic frameworks focusing on (1) formal argumentation structure, (2) normative quality, (3) nature and function of contributions within the dialog, (4) epistemic nature of reasoning, and (5) patterns and trajectories of participant interaction. Example analytic frameworks from each category are presented in detail rich enough to illustrate their nature and structure. This rich detail is intended to facilitate researchers’ identification of possible frameworks to draw upon in developing or adopting analytic methods for their own work. Each framework is applied to a shared segment of student dialog to facilitate this illustration and comparison process. Synthetic discussions of each category consider the frameworks in light of the underlying theoretical perspectives on argumentation, pedagogical goals, and online environmental structures. Ultimately the review underscores the diversity of perspectives represented in this research, the importance of clearly specifying theoretical and environmental commitments throughout the process of developing or adopting an analytic framework, and the role of analytic frameworks in the future development of online learning environments for argumentation

Temporary use of shape memory spinal rod in the treatment of scoliosis

NiTinol shape memory alloy is characterized by its malleability at low temperatures and its ability to return to a preconfigured shape above its activation temperature. This process can be utilized to assist in scoliosis correction. The goal of this retrospective study was to evaluate the clinical and radiographic results of intraoperative use of shape memory alloy rod in the correction of scoliosis. From May 2002 to September 2006, 38 scoliosis patients (ranging from 50° to 120°; 22 cases over 70°) who underwent shape memory alloy-assisted correction in our institute were reviewed. During the operation, a shape memory alloy rod served as a temporary correction tool. Following correction, the rod was replaced by a rigid rod. The mean blood loss at surgery was 680 ± 584 ml; the mean operative time was 278 ± 62 min. The major Cobb angle improved from an average 78.4° preoperatively to 24.3° postoperatively (total percent correction 71.4%). In 16 patients with a major curve <70° and flexibility of 52.7%, the deformity improved from 58.4° preoperatively to 12.3° postoperatively (percent correction, 78.9%). In 22 patients with a major curve >70° and flexibility of 25.6%, the deformity improved from 94.1° preoperatively to 30.1° postoperatively (percent correction, 68.1%). Only one case had a deep infection. There were no neurologic, vascular or correction-related complications such as screw pullout or metal fracture. The study shows that the intraoperative use of a shape memory rod is a safe and effective method to correct scoliosis

Multilevel analysis in CSCL Research

Janssen, J., Erkens, G., Kirschner, P. A., & Kanselaar, G. (2011). Multilevel analysis in CSCL research. In S. Puntambekar, G. Erkens, & C. Hmelo-Silver (Eds.), Analyzing interactions in CSCL: Methods, approaches and issues (pp. 187-205). New York: Springer. doi:10.1007/978-1-4419-7710-6_9CSCL researchers are often interested in the processes that unfold between learners in online learning environments and the outcomes that stem from these interactions. However, studying collaborative learning processes is not an easy task. Researchers have to make quite a few methodological decisions such as how to study the collaborative process itself (e.g., develop a coding scheme or a questionnaire), on the appropriate unit of analysis (e.g., the individual or the group), and which statistical technique to use (e.g., descriptive statistics, analysis of variance, correlation analysis). Recently, several researchers have turned to multilevel analysis (MLA) to answer their research questions (e.g., Cress, 2008; De Wever, Van Keer, Schellens, & Valcke, 2007; Dewiyanti, Brand-Gruwel, Jochems, & Broers, 2007; Schellens, Van Keer, & Valcke, 2005; Strijbos, Martens, Jochems, & Broers, 2004; Stylianou-Georgiou, Papanastasiou, & Puntambekar, chapter #). However, CSCL studies that apply MLA analysis still remain relatively scarce. Instead, many CSCL researchers continue to use ‘traditional’ statistical techniques (e.g., analysis of variance, regression analysis), although these techniques may not be appropriate for what is being studied. An important aim of this chapter is therefore to explain why MLA is often necessary to correctly answer the questions CSCL researchers address. Furthermore, we wish to highlight the consequences of failing to use MLA when this is called for, using data from our own studies

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs--liver, lung, skin, brain--are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing

Affordances, constraints and information flows as ‘leverage points’ in design for sustainable behaviour

Copyright @ 2012 Social Science Electronic PublishingTwo of Donella Meadows' 'leverage points' for intervening in systems (1999) seem particularly pertinent to design for sustainable behaviour, in the sense that designers may have the scope to implement them in (re-)designing everyday products and services. The 'rules of the system' -- interpreted here to refer to affordances and constraints -- and the structure of information flows both offer a range of opportunities for design interventions to in fluence behaviour change, and in this paper, some of the implications and possibilities are discussed with reference to parallel concepts from within design, HCI and relevant areas of psychology

Comparative analysis between shape memory alloy-based correction and traditional correction technique in pedicle screws constructs for treating severe scoliosis

The three-dimensional correction of severe rigid scoliosis has been improved by segmental pedicle screw instrumentation. However, there can be significant difficulty related to the use of a rigid rod, especially in the apex region of severe scoliosis. This study is a retrospective matched cohort study to evaluate the advantages of Nitinol shape memory alloy (SMA) rod-based correction by comparing the clinical and radiographic results obtained from using a temporary SMA rod and those from a standard rod in the correction of severe scoliosis. From May 2004 to September 2006, patients with matched curve type, ages at surgery, operative methods and fusion levels in our institute and instrumented with either SMA rods (n = 14) or traditional correction techniques (n = 16) were reviewed. In SMA group, the SMA rods served as a temporary intraoperative tool for deformity correction and were replaced by standard rods. The blood loss at surgery averaged 778 ± 285 ml in the traditional group and 585 ± 188 ml in the SMA group (P < 0.05). Operative time averaged 284 ± 53 min in the SMA group and 324 ± 41 min in the traditional group (P < 0.05). In the SMA group, the preoperative major curve was 92.6° ± 13.7° with a flexibility of 25.5 ± 7.3% was corrected to 29.4° ± 5.7° demonstrating a 68.4% immediate postoperative correction. In the traditional group, the preoperative major curve was 88.6° ± 14.6° with a flexibility of 29.3 ± 6.6% was corrected to 37.2° ± 7.3° demonstrating a 57.8% immediate postoperative correction. There was a statistic difference between the SMA group and traditional group in correction rate of the major thoracic curve. In the SMA group, one case suffered from deep infection 2 months postoperatively. In the traditional group, 6 of 16 cases suffered pedicle screw pull out or loosening during placement of the standard rod at the apex vertebrae on the concave side. In three cases, the mono-axial pedicle screws near the apex were abandoned and in five cases replaced with poly-axial pedicle screws. This study shows that the temporary use of SMA rod may reduce the operative time, blood loss, while improve the correction of the coronal plane when compared with standard techniques

How Coupling Determines the Entrainment of Circadian Clocks

Autonomous circadian clocks drive daily rhythms in physiology and behaviour. A network of coupled neurons, the suprachiasmatic nucleus (SCN), serves as a robust self-sustained circadian pacemaker. Synchronization of this timer to the environmental light-dark cycle is crucial for an organism's fitness. In a recent theoretical and experimental study it was shown that coupling governs the entrainment range of circadian clocks. We apply the theory of coupled oscillators to analyse how diffusive and mean-field coupling affects the entrainment range of interacting cells. Mean-field coupling leads to amplitude expansion of weak oscillators and, as a result, reduces the entrainment range. We also show that coupling determines the rigidity of the synchronized SCN network, i.e. the relaxation rates upon perturbation. %(Floquet exponents). Our simulations and analytical calculations using generic oscillator models help to elucidate how coupling determines the entrainment of the SCN. Our theoretical framework helps to interpret experimental data