A study on the temperature profile of bifurcation tunnel fire under natural ventilation.

This study simulated a series of bifurcation tunnel fire scenarios using the numerical code to investigate the temperature profile of bifurcation tunnel fire under natural ventilation. The bifurcation tunnel fire scenarios considered three bifurcation angles (30°, 45°, and 60°) and six heat release rates (HRRs) (5, 10, 15, 20, 25, and 30 MW). According to the simulation results, the temperature profile with various HRRs and bifurcation angles was described. Furthermore, the effects of bifurcation angles and HRRs on the maximum temperature under the bifurcation tunnel ceiling and the temperature decay along the longitudinal direction of the branch were investigated. According to the theoretical analysis, two prediction models were proposed. These models can predict a bifurcation tunnel fire's maximum temperature and longitudinal temperature decay in the branch. The results of this study could be valuable for modelling a bifurcation tunnel fire and benefit the fire engineering design of bifurcation tunnels.

Optimizations for identifying reference genes in bone and cartilage bioengineering.

BACKGROUND: Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) remains one of the best-established techniques to assess gene expression patterns. However, appropriate reference gene(s) selection remains a critical and challenging subject in which inappropriate reference gene selction can distort results leading to false interpretations. To date, mixed opinions still exist in how to choose the most optimal reference gene sets in accodrance to the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guideline. Therefore, the purpose of this study was to investigate which schemes were the most feasible for the identification of reference genes in a bone and cartilage bioengineering experimental setting. In this study, rat bone mesenchymal stem cells (rBMSCs), skeletal muscle tissue and adipose tissue were utilized, undergoing either chondrogenic or osteogenic induction, to investigate the optimal reference gene set identification scheme that would subsequently ensure stable and accurate interpretation of gene expression in bone and cartilage bioengineering. RESULTS: The stability and pairwise variance of eight candidate reference genes were analyzed using geNorm. The V0.15- vs. Vmin-based normalization scheme in rBMSCs had no significant effect on the eventual normalization of target genes. In terms of the muscle tissue, the results of the correlation of NF values between the V0.15 and Vmin schemes and the variance of target genes expression levels generated by these two schemes showed that different schemes do indeed have a significant effect on the eventual normalization of target genes. Three selection schemes were adopted in terms of the adipose tissue, including the three optimal reference genes (Opt3), V0.20 and Vmin schemes, and the analysis of NF values with eventual normalization of target genes showed that the different selection schemes also have a significant effect on the eventual normalization of target genes. CONCLUSIONS: Based on these results, the proposed cut-off value of Vn/n + 1 under 0.15, according to the geNorm algorithm, should be considered with caution. For cell only experiments, at least rBMSCs, a Vn/n + 1 under 0.15 is sufficient in RT-qPCR studies. However, when using certain tissue types such as skeletal muscle and adipose tissue the minimum Vn/n + 1 should be used instead as this provides a far superior mode of generating accurate gene expression results. We thus recommended that when the stability and variation of a candidate reference genes in a specific study is unclear the minimum Vn/n + 1 should always be used as this ensures the best and most accurate gene expression value is achieved during RT-qPCR assays.

HEALTH TECHNOLOGY ASSESSMENT METHODS GUIDELINES FOR MEDICAL DEVICES: HOW CAN WE ADDRESS THE GAPS? THE INTERNATIONAL FEDERATION OF MEDICAL AND BIOLOGICAL ENGINEERING PERSPECTIVE.

OBJECTIVES: Current health technology assessment (HTA) methods guidelines for medical devices may benefit from contributions by biomedical and clinical engineers. Our study aims to: (i) review and identify gaps in the current HTA guidelines on medical devices, (ii) propose recommendations to optimize the impact of HTA for medical devices, and (iii) reach a consensus among biomedical engineers on these recommendations. METHODS: A gray literature search of HTA agency Web sites for assessment methods guidelines on devices was conducted. The International Federation of Medical and Biological Engineers (IFMBE) then convened a structured focus group, with experts from different fields, to identify potential gaps in the current HTA guidelines, and to develop recommendations to fill these perceived gaps. The thirty recommendations generated from the focus group were circulated in a Delphi survey to eighty-five biomedical and clinical engineers. RESULTS: Thirty-two panelists, from seventeen countries, participated in the Delphi survey. The responses showed a strong agreement on twenty-seven of thirty recommendations. Some uncertainties remain about the methods to accurately assess the effectiveness and safety, and interoperability of a medical device with other devices or within the clinical setting. CONCLUSIONS: As medical devices differ from drug therapies, current HTA methods may not accurately reflect the conclusions of their assessment. Recommendations informed by the focus group discussions and Delphi survey responses aimed to address the perceived gaps, and to provide a more integrated approach in medical device assessments in combining engineering with other perspectives, such as clinical, economic, patient, human factors, ethical, and environmental.

Standardization in synthetic biology: an engineering discipline coming of age.

BACKGROUND: Leaping DNA read-and-write technologies, and extensive automation and miniaturization are radically transforming the field of biological experimentation by providing the tools that enable the cost-effective high-throughput required to address the enormous complexity of biological systems. However, standardization of the synthetic biology workflow has not kept abreast with dwindling technical and resource constraints, leading, for example, to the collection of multi-level and multi-omics large data sets that end up disconnected or remain under- or even unexploited. PURPOSE: In this contribution, we critically evaluate the various efforts, and the (limited) success thereof, in order to introduce standards for defining, designing, assembling, characterizing, and sharing synthetic biology parts. The causes for this success or the lack thereof, as well as possible solutions to overcome these, are discussed. CONCLUSION: Akin to other engineering disciplines, extensive standardization will undoubtedly speed-up and reduce the cost of bioprocess development. In this respect, further implementation of synthetic biology standards will be crucial for the field in order to redeem its promise, i.e. to enable predictable forward engineering.

Aplicación de la mecánica de fluidos y la simulación: tracto urinario y catéteres ureterales / Application of fluid mechanics and simulation: urinary tract and ureteral catheters

El comportamiento de la orina durante su transporte, desde la pelvis renal hasta la vejiga, tiene un gran interés para los urólogos. El conocimiento de las diferentes variables físicas y su interrelación, en movimientos fisiológicos y patologías, ayudará a un mejor diagnóstico y tratamiento. El objetivo de este capítulo es exponer y acercar al mundo clínico los conceptos físicos y sus relaciones básicas más relevantes en el transporte de orina. Para ello, se explica el movimiento de la orina durante una peristalsis, una obstrucción ureteral y un uréter tutorizado con un catéter ureteral. Esta explicación se basa en dos herramientas muy utilizadas en bioingeniería: el análisis teórico a través de la Teoría de los Medios Continuos y la Mecánica de Fluidos y la simulación computacional que ofrece una solución práctica de cada uno de los escenarios. Además, se repasan otras aportaciones de la bioingeniería al campo de la Urología, como la simulación física o las técnicas de fabricación aditiva y sustractiva. Finalmente, se enumeran las limitaciones actuales de estas herramientas y las líneas de desarrollo tecnológico con más proyección. CONCLUSIÓN: Se pretende que este capítulo ayude a los urólogos a comprender algunos conceptos importantes de bioingeniería, fomentando la colaboración multidisciplinar para ofrecer herramientas complementarias que les ayuden en el diagnóstico y el tratamiento de enfermedades

The mechanics of urine during its transport from the renal pelvis to the bladder is of great interest for urologists. The knowledge of the different physical variables and their interrelationship, both in physiologic movements and pathologies, will help a better diagnosis and treatment. The objective of this chapter is to show the physics principles and their most relevant basic relations in urine transport, and to bring them over the clinical world. For that, we explain the movement of urine during peristalsis, ureteral obstruction and in a ureter with a stent. This explanation is based in two tools used in bioengineering: the theoretical analysis through the Theory of concontinuous media and Ffluid mechanics and computational simulation that offers a practical solution for each scenario. Moreover, we review other contributions of bioengineering to the field of Urology, such as physical simulation or additive and subtractive manufacturing techniques. Finally, we list the current limitations for these tools and the technological development lines with more future projection. CONCLUSIONS: In this chapter we aim to help urologists to understand some important concepts of bioengineering, promoting multidisciplinary cooperation to offer complementary tools that help in diagnosis and treatment of diseases

Harnessing QbD, Programming Languages, and Automation for Reproducible Biology.

Building robust manufacturing processes from biological components is a task that is highly complex and requires sophisticated tools to describe processes, inputs, and measurements and administrate management of knowledge, data, and materials. We argue that for bioengineering to fully access biological potential, it will require application of statistically designed experiments to derive detailed empirical models of underlying systems. This requires execution of large-scale structured experimentation for which laboratory automation is necessary. This requires development of expressive, high-level languages that allow reusability of protocols, characterization of their reliability, and a change in focus from implementation details to functional properties. We review recent developments in these areas and identify what we believe is an exciting trend that promises to revolutionize biotechnology.

The proximal medial sural nerve biopsy model: a standardised and reproducible baseline clinical model for the translational evaluation of bioengineered nerve guides.

Autologous nerve transplantation (ANT) is the clinical gold standard for the reconstruction of peripheral nerve defects. A large number of bioengineered nerve guides have been tested under laboratory conditions as an alternative to the ANT. The step from experimental studies to the implementation of the device in the clinical setting is often substantial and the outcome is unpredictable. This is mainly linked to the heterogeneity of clinical peripheral nerve injuries, which is very different from standardized animal studies. In search of a reproducible human model for the implantation of bioengineered nerve guides, we propose the reconstruction of sural nerve defects after routine nerve biopsy as a first or baseline study. Our concept uses the medial sural nerve of patients undergoing diagnostic nerve biopsy (≥ 2 cm). The biopsy-induced nerve gap was immediately reconstructed by implantation of the novel microstructured nerve guide, Neuromaix, as part of an ongoing first-in-human study. Here we present (i) a detailed list of inclusion and exclusion criteria, (ii) a detailed description of the surgical procedure, and (iii) a follow-up concept with multimodal sensory evaluation techniques. The proximal medial sural nerve biopsy model can serve as a preliminary nature of the injuries or baseline nerve lesion model. In a subsequent step, newly developed nerve guides could be tested in more unpredictable and challenging clinical peripheral nerve lesions (e.g., following trauma) which have reduced comparability due to the different nature of the injuries (e.g., site of injury and length of nerve gap).

Synthetic biology: evolution or revolution? A co-founder's perspective.

In this article, we relate the story of Synthetic Biology's birth, from the perspective of a co-founder, and consider its original premise--that standardization and abstraction of biological components will unlock the full potential of biological engineering. The standardization ideas of Synthetic Biology emerged in the late 1990s from a convergence of research on cellular computing, and were motivated by an array of applications from tissue regeneration to bio-sensing to mathematical programming. As the definition of Synthetic Biology has grown to be synonymous with Biological Engineering and Biotechnology, the field has lost sight of the fact that its founding premise has not yet been validated. While the value of standardization has been proven in many other engineering disciplines, none of them involve self-replicating systems. The engineering of self-replicating systems will likely benefit from standardization, and also by embracing the forces of evolution that inexorably shape such systems.

Risk-based scientific approach for determination of extractables/leachables from biomanufacturing of antibody-drug conjugates (ADCs).

Recent developments in biopharmaceutical processes twined with a desire to remove cleaning and cross-contamination issues from drug production have led to the widespread introduction of single-use technologies and systems within operations. One key area that end users need to address with the advent of these single-use solutions is the potential for increased levels of extractables and leachables within a process, which need to be evaluated and understood as part of any regulatory submission. A science-based and practical method for characterization of extractables and leachables from single-use systems used in manufacturing antibody-drug conjugates has been developed and described in detail. This risk-based approach minimizes the amount of test work while meeting the regulatory requirements to ensure the drug safety and quality. The test design is optimized and the analytical methods (gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and inductively coupled plasma/mass spectrometry) are shown to be suitable for quantifying and identifying the extracted chemical compounds. Application of this characterization method speeds up the filing process for qualification and validation of single-use systems used in bioprocesses.

Harnessing our very life.

The Aristotelian ideas of nature (physis) and technology (techné) are taken as a starting point for understanding what it would mean for technology to be truly living. Heidegger's critique of the conflation of scientific and technological thinking in the current era is accepted as demonstrating that humanity does not have a deep enough appreciation of the nature of life to harness its essence safely. Could the vision of harnessing life be realized, which we strongly doubt, living technology would give selected humans transforming powers that could be expected to exacerbate, rather than solve, current global problems. The source of human purposefulness, and hence of both technology and ethics, is identified in nature's emergent capability to instantiate informational representations in material forms. Ethics that are properly grounded in an appreciation of intrinsic value, especially that of life, demand that proposals to give humanity the capabilities of living technology address the social, political, economic, and environmental problems inherent in its development and potential deployment. Before any development is embarked on, steps must be taken to avoid living technology, whatever the term eventually designates, becoming available for destructive or antisocial purposes such as those that might devastate humanity or irrevocably damage the natural world.

The good of two worlds: increasing complexity in cell-free systems.

In vitro biocatalytic systems have moved far beyond established uses in food, diagnostic, and chemical applications. As new strategies to construct and manage multiple enzymes in ever more complex systems are developed, novel applications emerge. In the field of chemistry, complex protein networks are applied to enable the production of fine chemicals, such as dihydroxyacetone phosphate, and even bulk chemicals, such as biofuels, from cheap sugars. Cell-free protein synthesis is applied to expanding protein and nucleic acid biochemistry and enabling novel assay formats, while programmable DNA-circuits can be exploited to engineer sensitive detection methods. Novel developments in chemical analytics such as real-time mass spectrometry to follow the metabolism online, directed physical assembly of network members facilitating substrate channeling, and encapsulation forming biofunctional subunits enable a better control and potential for optimization.

BioInnovate Ireland--fostering entrepreneurial activity through medical device innovation training.

In the midst of a rich environment for medical device development and manufacturing, universities can play a critical role by developing relevant training programs to produce entrepreneurs who can be efficient and successful in creating early stage companies by understanding deeply the issues involved in creating a useful device, how to raise money, designing early clinical studies and locating manufacturing partners.

Tightening of ethical standards in bioengineering brings teaching the fore: in a realm noted for puzzlement, a rare consensus is achieved.

While the practice of ethical pondering has a formal academic history more than several thousand years old, and its pedigree within the human heart is undoubtedly much older, the somewhat specialized field of bioethics goes back approximately only 50 years in the United States. And while practitioners in the field-known as much for their painstaking pondering as for their acrimonious tendency to disagree-rarely achieve quick consensus on the pressing issues of the day, it would appear that in the United States we have reached some consensus on the best way of teaching biomedical ethics to undergraduate students.

Biomarcadores de imagen, imagen cuantitativa y bioingeniería / Imaging biomarkers, quantitative imaging, and bioengineering

Los biomarcadores de imagen definen características objetivas extraídas de las imágenes médicas, relacionadas con procesos biológicos normales, enfermedades o respuestas terapéuticas. Para desarrollar un biomarcador de imagen es necesario realizar una serie de pasos destinados a validar su relación con la realidad estudiada y controlar su validez, tanto clínica como técnica. Este proceso incluye la definición de pruebas de concepto y de mecanismo; la adquisición estandarizada y optimizada de imágenes anatómicas, funcionales y moleculares; el análisis de los datos mediante modelos computacionales; la visualización adecuada de los resultados; la obtención de medidas estadísticas apropiadas; y la realización de pruebas de principio, eficacia y efectividad. Nuestro objetivo en este trabajo es mostrar los pasos que deben establecerse para aplicar adecuadamente los biomarcadores de imagen, desde su concepción teórica hasta su implantación asistencial, en un entorno hospitalario. Para ello se planteará como ejemplo la valoración de la angiogénesis del cartílago articular (AU)

Imaging biomarkers define objective characteristics extracted from medical images that are related to normal biological processes, diseases, or the response to treatment. To develop an imaging biomarker, it is necessary to carry out a series of steps to validate its relation with the reality studied and to check its clinical and technical validity. This process includes defining tests for the concepts and mechanisms; obtaining standardized and optimized anatomic, functional, and molecular images; analyzing the data with computer models; displaying data appropriately; obtaining the appropriate statistic measures; and conducting tests on the principle, efficacy, and effectiveness. In this article, we aim to explain the steps that must be established to enable biomarkers to be correctly applied, from their theoretical conception to their clinical implementation. To this end, we use the evaluation of angiogenesis in articular cartilage as an example (AU)

Maintaining a relevant, up-to-date capstone design course.

Senior capstone design courses can be extremely helpful in preparing biomedical engineering students for careers in engineering and other fields. They allow students to develop communication, teamwork, and other transferable technical and nontechnical skills. They can also make students aware of the (1) legal, regulatory, economic, environmental, and social/political constraints of medical device design, (2) contemporary issues related to biomedical engineering and health care, and (3) the latest trends and tools in new product development and project management.

The objective evaluation of the severity of psoriatic scales with desquamation collecting tapes and image analysis.

BACKGROUND: Assessment of psoriatic scales is important to determine the severity of psoriasis. However, there are very limited numbers of objective, quantitative and observer-independent tools for measuring the severity of psoriasis. OBJECTIVE: To determine whether the bioengineering parameters of the psoriatic scale can be used to assess the severity of psoriasis instead of the psoriatic severity index of scales (PSIs) score. METHODS: Thirty-four patients with psoriasis were included. A representative lesion from each patient was selected and bioengineering parameters were measured using the Corneofix(®). Simultaneously, the severity of the scales was assessed by the PSIs score using clinical photographs of the lesions. In addition, skin color and elasticity parameters were also measured using the Colorimeter(®), the Mexameter(®) and the Cutometer(®). RESULTS: Statistical differences in the scale parameters were observed between the PSIs 2 and 3 scores. Among the scale parameters, the percent area and area in µm(2) were negatively correlated with the PSIs score. In addition, the Colorimeter(®) a, b parameters and the Cutometer(®) R9 parameters were significantly correlated with the PSIs score. CONCLUSIONS: The results of this study showed that the severity of psoriatic scales could be measured objectively using the Corneofix(®).

Allogeneic single-donor cryoseal produced from fresh-frozen quarantine apheresis plasma as alternative for multidonor or autologous fibrin sealants.

BACKGROUND: Fibrin sealant is a human blood product consisting of two components: cryoprecipitate and thrombin. Commercial fibrin sealants are produced from multidonors, increasing the viral risk, and contain fibrinolytic inhibitors such as tranexamic acid or bovine aprotinin. Autologous fibrin sealants reduce the viral risk and are mostly produced during a surgical procedure or well in advance. Alternatively, the allogeneic single-donor fibrin sealant cryoseal can be used. In this study cryoseal was characterized and the manufacturing consistency of the production process was investigated. STUDY DESIGN AND METHODS: Cryoseal was produced from plasma collected on apheresis machines using a commercial device. In a research setting the protein composition and recovery were determined. Also, the manufacturing consistency of the production process was tested in a research setting as well as in a routine setting. RESULTS: In the research setting all produced cryoseal met the quality control requirements of a clotting time of less than 10 seconds and the presence of Factor (F)XIII (qualitative). In the routine setting, one procedure per year did not meet these requirements. The protein composition showed the following mean ± standard deviation (%recovery) results: thrombin 25.7 ± 11.1 IU/mL, fibrinogen 19.9 ± 4.6 (15%) mg/mL, FVIII 15.6 ± 5.4 (44%) IU/mL, FXIII 2.7 ± 0.7 (6%) IU/mL, and plasminogen 1.8 ± 0.2 (4%) U/mL. In both research and routine settings the production process resulted in a consistent product. CONCLUSION: The cryoseal manufacturing process resulted in a consistent product, which meets the predetermined specifications. The single-donor origin and the absence of fibrinolytic inhibitors make cryoseal a good alternative for multidonor and autologous fibrin sealants.

Quality control and analytical methods for baculovirus-based products.

Recombinant baculoviruses (rBac) are used for many different applications, ranging from bio-insecticides to the production of heterologous proteins, high-throughput screening of gene functions, drug delivery, in vitro assembly studies, design of antiviral drugs, bio-weapons, building blocks for electronics, biosensors and chemistry, and recently as a delivery system in gene therapy. Independent of the application, the quality, quantity and purity of rBac-based products are pre-requisites demanded by regulatory authorities for product licensing. To guarantee maximization utility, it is necessary to delineate optimized production schemes either using trial-and-error experimental setups ("brute force" approach) or rational design of experiments by aid of in silico mathematical models (Systems Biology approach). For that, one must define all of the main steps in the overall process, identify the main bioengineering issues affecting each individual step and implement, if required, accurate analytical methods for product characterization. In this review, current challenges for quality control (QC) technologies for up- and down-stream processing of rBac-based products are addressed. In addition, a collection of QC methods for monitoring/control of the production of rBac derived products are presented as well as innovative technologies for faster process optimization and more detailed product characterization.