Mathematical and computational models for bone tissue engineering in bioreactor systems

Research into cellular engineered bone grafts offers a promising solution to problems associated with the currently used auto- and allografts. Bioreactor systems can facilitate the development of functional cellular bone grafts by augmenting mass transport through media convection and shear flow-induced mechanical stimulation. Developing successful and reproducible protocols for growing bone tissue in vitro is dependent on tuning the bioreactor operating conditions to the specific cell type and graft design. This process, largely reliant on a trial-and-error approach, is challenging, time-consuming and expensive. Modelling can streamline the process by providing further insight into the effect of the bioreactor environment on the cell culture, and by identifying a beneficial range of operational settings to stimulate tissue production. Models can explore the impact of changing flow speeds, scaffold properties, and nutrient and growth factor concentrations. Aiming to act as an introductory reference for bone tissue engineers looking to direct their experimental work, this article presents a comprehensive framework of mathematical models on various aspects of bioreactor bone cultures and overviews modelling case studies from literature

Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan

Extraluminal Amyloidoma of the Pelvic Cavity Causing Large Bowel Obstruction

Amyloidosis is a group of diverse disorders that fall into several major categories: primary, secondary, dialysis-associated, and hereditary forms. Clinically, amyloidosis may be categorized as localized or systemic. The gastrointestinal tract is among the most common places for deposition of amyloid, but large, localized amyloid deposits are an uncommon occurrence and rarely cause extraluminal bowel compression resulting in obstruction as was seen in the case presented in this clinical scenario

Findings from the Longitudinal CINRG Becker Natural History Study

BACKGROUND: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. OBJECTIVE: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials. METHODS: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes. RESULTS: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter. CONCLUSIONS: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset

Volunteered information on nature-based solutions — Dredging for data on deculverting

Much has been written about the potential contribution of citizen-science approaches to further urban environmental sustainability, and associated interventions such as nature-based solutions (NBS). Engagements between researchers and stakeholders relying on bottom-up information provision, for instance community mapping, are often purported to play a vital role in developing shared knowledge, achieving greater impact and stimulating innovation. However, relatively few studies within the realm of NBS have reported on experiences in using volunteered information, or their results. This reflects an important gap, not least because of the proliferation of proposals and bids that rely upon or integrate such methods into their approach. We report on experiences with gathering information using a ‘bottom-up’ map-based wiki tool, which effectively sought to crowd-source data, contributed by members of the public and professional stakeholders. As we approach the milestone of ‘10 years on’ from the inception of the website www.daylighting.org.uk, we reflect on our approach, the opportunities presented, constraints encountered, progress made and results delivered. This is contrasted with other resources and data-gathering projects having similar aims for different urban NBS. Findings are presented on the substantive issue of the uptake of deculverting as a particular form of NBS, including land-use contexts, scheme costs and achievement of stated objectives. Reflections are given on potential contributions of such methods in relation to other, more established approaches and new techniques in urban knowledge co-productio

Analysing energy innovation portfolios from a systemic perspective

A systemic perspective on energy innovation is required to design effective portfolios of directed innovation activity. We contribute a standardised set of technology-specific indicators which describe processes throughout the energy technology innovation system, ranging from patents and publications to policy mixes, collaborative activity, and market share. Using these indicators, we then conceptualise and develop benchmark tests for three portfolio design criteria: balance, consistency, and alignment. Portfolio balance refers to the relative emphasis on specific technologies. Portfolio consistency refers to the relative emphasis on related innovation system processes. Portfolio alignment refers to the relative emphasis on innovation system processes for delivering targeted outcomes. We demonstrate the application of these benchmark tests using data for the EU's Strategic Energy Technology (SET) Plan which spans six technology fields. We find the SET Plan portfolio generally performs well particularly in areas over which portfolio managers have direct influence such as RD&D funding. However we also identify potential areas of imbalance, inconsistency, and misalignment which warrant further attention and potential redress by portfolio managers. Overall, we show how energy innovation portfolios can be analysed from a systemic perspective using a replicable, standardised set of measures of diverse innovation system processes

Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI

Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 mice in the widely used model of transient middle cerebral artery occlusion (tMCAO) by multimodal ultra-high field magnetic resonance imaging (MRI)

Machine learning for the Zwicky transient facility

The Zwicky Transient Facility is a large optical survey in multiple filters producing hundreds of thousands of transient alerts per night. We describe here various machine learning (ML) implementations and plans to make the maximal use of the large data set by taking advantage of the temporal nature of the data, and further combining it with other data sets. We start with the initial steps of separating bogus candidates from real ones, separating stars and galaxies, and go on to the classification of real objects into various classes. Besides the usual methods (e.g., based on features extracted from light curves) we also describe early plans for alternate methods including the use of domain adaptation, and deep learning. In a similar fashion we describe efforts to detect fast moving asteroids. We also describe the use of the Zooniverse platform for helping with classifications through the creation of training samples, and active learning. Finally we mention the synergistic aspects of ZTF and LSST from the ML perspective