Development of multiwave-based bioprinting technology

Pluripotent stem cells (PSCs) are the most favourable sources of cells for tissue engineering applications due to their unique potency and self-renewal characteristics however they are quite fragile and can be directed to differentiate erroneously by the application of external forces. A novel multi-nozzle valve-based bioprinting platform was developed that was able to position droplets of bio-ink – such as cells in suspension – with high spatial accuracy and low impact. Volumes as low as 2 nL were successfully dispensed. Several different versions of the machine were created before the final machine was made integrating improvements and solutions to problems encountered during development. A complete evaluation of cell compatibility was carried out in order to quantify the response of cells to the bioprinting process. In the first ever study of this kind, the viability and pluripotency of human embryonic and induced pluripotent stem cells was investigated post-printing and were found to be almost completely unaffected by the bioprinting process. Many cells require a 3D culture environment in order to maintain their in vivo functions. A hybrid bioprinted-hanging-droplet technique was used to create uniform spheroid aggregates of programmable sizes from PSCs which could be used to direct PSC differentiation or as building blocks for tissue generation. Hydrogels can also be used to recreate the 3D in vivo cellular environment using the bioprinter. Alginate and hybrid polypeptide-DNA hydrogels were used, the latter for the first time with a bioprinting platform. Complex 3D structures could be created in a layer-by-layer approach with programmable heterogeneous properties throughout. Cells were added to the hydrogel precursor solution and used to bioprint 3D structures. The cells were found to be functional and highly viable while being encapsulated throughout the 3D structure of the bioprinted hydrogel which will allow the future creation of more accurate human tissue models. PSCs were successfully directed to differentiate into hepatocyte-like cells. It was shown that the bioprinting process did not interrupt or alter the pre-programmed differentiation of the cells which means that these cells can be patterned in 3D using the bioprinter while differentiating, greatly speeding up the creation of mini-liver tissue. Hepatic stellates and HUVECs were co-cultured with the hepatocyte-like cells in various ratios in an attempt to improve their hepatic function. However, no clear improvement in cytochrome P450 activity was observed indicating that further optimisation is required in this area

Development of multivalve-based bioprinting technology

Pluripotent stem cells (PSCs) are the most favourable sources of cells for tissue engineering applications due to their unique potency and self-renewal characteristics however they are quite fragile and can be directed to differentiate erroneously by the application of external forces. A novel multi-nozzle valve-based bioprinting platform was developed that was able to position droplets of bio-ink – such as cells in suspension – with high spatial accuracy and low impact. Volumes as low as 2 nL were successfully dispensed. Several different versions of the machine were created before the final machine was made integrating improvements and solutions to problems encountered during development. A complete evaluation of cell compatibility was carried out in order to quantify the response of cells to the bioprinting process. In the first ever study of this kind, the viability and pluripotency of human embryonic and induced pluripotent stem cells was investigated post-printing and were found to be almost completely unaffected by the bioprinting process. Many cells require a 3D culture environment in order to maintain their in vivo functions. A hybrid bioprinted-hanging-droplet technique was used to create uniform spheroid aggregates of programmable sizes from PSCs which could be used to direct PSC differentiation or as building blocks for tissue generation. Hydrogels can also be used to recreate the 3D in vivo cellular environment using the bioprinter. Alginate and hybrid polypeptide-DNA hydrogels were used, the latter for the first time with a bioprinting platform. Complex 3D structures could be created in a layer-by-layer approach with programmable heterogeneous properties throughout. Cells were added to the hydrogel precursor solution and used to bioprint 3D structures. The cells were found to be functional and highly viable while being encapsulated throughout the 3D structure of the bioprinted hydrogel which will allow the future creation of more accurate human tissue models. PSCs were successfully directed to differentiate into hepatocyte-like cells. It was shown that the bioprinting process did not interrupt or alter the pre-programmed differentiation of the cells which means that these cells can be patterned in 3D using the bioprinter while differentiating, greatly speeding up the creation of mini-liver tissue. Hepatic stellates and HUVECs were co-cultured with the hepatocyte-like cells in various ratios in an attempt to improve their hepatic function. However, no clear improvement in cytochrome P450 activity was observed indicating that further optimisation is required in this area

Trust and trustworthiness

What is it to trust someone? What is it for someone to be trustworthy? These are the two main questions that this paper addresses. There are various situations that can be described as ones of trust, but this paper considers the issue of trust between individuals. In it, I suggest that trust is distinct from reliance or cases where someone asks for something on the expectation that it will be done due to the different attitude taken by the trustor. I argue that the trustor takes Holton's 'participant stance' and this distinguishes trust from reliance. I argue that trustworthiness is different from reliability and that an account of trustworthiness cannot be successful whilst ignoring the point that aligning trustworthiness with reliability removes the virtue from being trustworthy. On the question of what it is distinguishes trustworthiness from reliability, I argue that the distinction is in the opportunity for the trustee to act against the wishes of the trustor and the trustee's consideration of the value of the trust that has been placed in them by the trustor

Eye-Tracking in the Study of Visual Expertise: Methodology and Approaches in Medicine

Eye-tracking is the measurement of eye motions and point of gaze of a viewer. Advances in this technology have been essential to our understanding of many forms of visual learning, including the development of visual expertise. In recent years, these studies have been extended to the medical professions, where eye-tracking technology has helped us to understand acquired visual expertise, as well as the importance of visual training in various medical specialties. Medical decision-making involves a complex interplay between knowledge and sensory information, and the study of eye-movements can reveal the mechanisms involved in acquiring the visual component of these skills. Eye-tracking studies have even been extended to develop computational models of procedures for “expert” skill assessment, and to eliminate potential sources of error in image-based diagnostics. This review will examine the current eye-tracking frontier for the study of visual expertise, with specific application to medical professions

Hate or glory: a categorical and experimental consideration of Bronze Age halberds in Scotland in relation to MBA weaponry

Despite being one of the largest collections of their type in Europe, the Early Bronze Age halberds in Scotland have not been catalogued or analysed since Coles’ 1968-9 work. Accordingly, every halberd in Scotland was recorded and catalogued to assess the size and level of preservation of the assemblage. Experimental work using a replica halberd was designed to determine the combat capabilities and limitations of the weapon, and to determine the extent of damage inflicted on the blades during interpersonal combat. Prior to this, experiments using a replica Middle Bronze Age dirk from Friarton, Perthshire were designed to establish the methodology and experimental protocol. During the creation of the experimental protocols, parameters considered included the design and manufacture of the replica, the human tissue analogue used, the layout and audience for the experiment, and the subsequent data analysis. The experimentally derived data on the dirk were compared with extant catalogue data to investigate whether the damage inflicted on the replica blade could be observed on the prehistoric dirks. Following the methodology and experimental protocol refined following the investigations with the replica dirk, the replica halberd experiments were then undertaken, first using SynboneTM as a skeletal tissue proxy, and secondly a pig carcass as a soft tissue proxy. The damage to the replica halberd blades observed following the experiments was analysed and compared to the newly-catalogued prehistoric halberd assemblage An interpretative model synthesising all the halberd data was then derived as one possible interpretation as to the uses and distribution of the halberds; the halberds were shown experimentally to be functional combat weapons, able to be used effectively with no great amount of training or mobility, and the mending and conservation evidence in the prehistoric assemblage is hypothesised to be linked to their role as combat and political power proxies in long-distance communication networks across northern Europe

Injury To Skeletal Muscles Of Mice By Forced Lengthening During Contractions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109942/1/eph1989745661.pd

Protein synthesis in skeletal muscle following acute exhaustive exercise

Cell-free and whole-tissue protein synthesis was studied in skeletal muscle of untrained male guinea pigs that had undergone a treadmill run to exhaustion. Experiments using explants from the gastrocnemius muscle maintained in organ culture demonstrated that the ability of the acutely exercised muscle to incorporate amino acids into protein had increased. Compared to polyribosomes prepared from several lower hind limb muscles of nonexercised guinea pigs, polyribosomes from the same muscle in exhausted guinea pigs had incorporated almost 50% more radioactive leucine into protein. However, the polysome profiles of control and exercised muscle were identical, and no difference in the total polysome RNA content could be detected. The efficiency of in-vitro protein synthesis using washed membrane-bound polyribosomes (microsomes) isolated from acutely exercised skeletal muscle was 50% greater than with microsomes from rested control muscle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50128/1/880020403_ftp.pd

Exploring Meaningful Patient Engagement in ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness).

BackgroundGenuine patient engagement can improve research relevance, impact and is required for studies using the National Patient-Centered Clinical Research Network including major multicenter research projects. It is unclear, however, how best to integrate patients into governance of such projects.MethodsADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness) is the first major multicenter research project to be conducted in National Patient-Centered Clinical Research Network. Here, we provide a description of how we implemented patient engagement in ADAPTABLE thus far, including a description of committee structures and composition, first-hand patient testimonials, specific contributions, and lessons learned during the planning and early implementation of ADAPTABLE.ResultsWe recruited 1 patient leader from 6 of the 7 enrolling networks to serve on a Patient Review Board for ADAPTABLE, supported the Board with an experienced patient engagement team including an "investigator-advocate" not otherwise involved in the trial, and facilitated bidirectional communication between the Board and ADAPTABLE Coordinating Center. The Board has reviewed and provided substantial input on the informed consent procedure, recruitment materials, patient portal design, and study policy including compensation of participants. Although it was "too late" for some suggested modifications, most modifications suggested by the patient leaders have been implemented, and they are enthusiastic about the study and their role. The patient leaders also attend Steering and Executive Committee calls; these experiences have been somewhat less productive.ConclusionsWith adequate support, a cadre of committed patient leaders can provide substantial value to design and implementation of a major multicenter clinical trial

3D bioprint me : a socioethical view of bioprinting human organs and tissues

In this article, we review the extant social science and ethical literature on three-dimensional (3D) bioprinting. 3D bioprinting has the potential to be a ‘game-changer’, printing human organs on demand, no longer necessitating the need for living or deceased human donation or animal transplantation. Although the technology is not yet at the level required to bioprint an entire organ, 3D bioprinting may have a variety of other mid-term and short-term benefits that also have positive ethical consequences, for example, creating alternatives to animal testing, filling a therapeutic need for minors and avoiding species boundary crossing. Despite a lack of current socioethical engagement with the consequences of the technology, we outline what we see as some preliminary practical, ethical and regulatory issues that need tackling. These relate to managing public expectations and the continuing reliance on technoscientific solutions to diseases that affect high-income countries. Avoiding prescribing a course of action for the way forward in terms of research agendas, we do briefly outline one possible ethical framework ‘Responsible Research Innovation’ as an oversight model should 3D bioprinting promises are ever realised. 3D bioprinting has a lot to offer in the course of time should it move beyond a conceptual therapy, but is an area that requires ethical oversight and regulation and debate, in the here and now. The purpose of this article is to begin that discussion

Water and health. [Chapter 6 of 'Sustainable water: chemical science priorities summary report']

Water transports contaminants, including inorganic, organic and biological materials, from various sources both natural and man-made. Such contaminants can enter the human body via water by ingestion, inhalation of water droplets and contact, particularly with broken skin. Water borne diseases have historically had the greatest impact upon human health and continue to contribute to millions of deaths globally per year. Water use and sanitation in the form of hygiene practices act as an important barrier to disease transmission. Disease incidences in countries without basic water and sanitation services are estimated to be eleven times higher for than those in areas with clean water, hygiene practices, and the safe disposal of human wastes. Naturally occurring arsenic compounds (in particular toxic organic species) contaminate substantial groundwater sources. The most seriously affected areas in Sustainable Water: Chemical Science Priorities Royal Society of Chemistry report the world are in India and Bangladesh. Here, 60–100 million people are currently at risk of poisoning as a result of drinking contaminated groundwater where the arsenic arises from the natural bedrock geology. There is a need for portable field-testing kits that are quick, accurate, cheap and reliable that can support remediation efforts. Additionally there is a need for arsenic mitigation technologies that are effective and appropriate for use by local populations. There is also a growing problem with uranium contamination of groundwater, particularly in Eastern Europe. Society is reliant upon man-made chemicals, particularly for food and health, and inevitably such chemicals end up in water systems. Typically these chemical contaminants are either neurotoxins, pharmaceutically active or endocrine disruptors. Additionally there is growing concern over multiple chemical sensitivity1, although scientific evidence is insufficient to prove or disprove this theory at this time. There are two specific problems with man-made chemicals in wastewater: firstly, treatment plants are not designed to remove these chemical products; secondly, chemicals entrained in sediments can be mobilised by chemical and biological processes. Traditionally, pollution by man-made chemicals is reduced by either dilution or through end of pipe remediation technologies. This can be minimised by adopting good practice and integrated pollution prevention and control. This would include measures such as minimising the quantity of materials used and recovering unused materials. Additionally, industrial waste streams should be concentrated as far as possible and mixtures of materials should be avoided, as this will require additional treatment steps and effort