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Collagen scaffolds as a tool for understanding the biological effect of silicates
Dietary silicon is essential in the maintenance of bone and cartilage. However, the mechanism by which silicon, in the form of silicates, triggers a biological response has never been uncovered. Here we demonstrate the incorporation of orthosilicic acid (Si(OH)4), the form of silicon in the body, within collagen scaffolds for use as an in vitro platform to identify key genes affected by silicates. Ice-templated collagenâsilicate scaffolds, containing 0.21 wt% silicon, were validated by examining the mRNA levels for an array of genes in human osteoblasts and mesenchymal stromal cells (MSC) after 48 h in culture. Several novel genes, such as tumor necrosis factor alpha (TNF), were identified as having potential links to orthosilicic acid, verifying that collagenâsilicate scaffolds are a versatile platform for identifying novel mechanisms in which silicates regulate musculoskeletal tissue.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust , ERC Advanced Grant 320598 3D-E and from the National Institute for Health Research. RJ is supported by the Medical Research Council (Grant number MC_US_A090_0008/Unit Programme number U1059).This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0167577X15300203#
Adapting tissue-engineered in vitro CNS models for high-throughput study of neurodegeneration
Neurodegenerative conditions remain difficult to treat, with the continuing failure to see therapeutic research successfully advance to clinical trials. One of the obstacles that must be overcome is to develop enhanced models of disease. Tissue engineering techniques enable us to create organised artificial central nervous system tissue that has the potential to improve the drug development process. This study presents a replicable model of neurodegenerative pathology through the use of engineered neural tissue co-cultures that can incorporate cells from various sources and allow degeneration and protection of neurons to be observed easily and measured, following exposure to neurotoxic compounds - okadaic acid and 1-methyl-4-phenylpyridinium. Furthermore, the technology has been miniaturised through development of a mould with 6 mm length that recreates the advantageous features of engineered neural tissue co-cultures at a scale suitable for commercial research and development. Integration of human-derived induced pluripotent stem cells aids more accurate modelling of human diseases, creating new possibilities for engineered neural tissue co-cultures and their use in drug screening
Homeostatic competition drives tumor growth and metastasis nucleation
We propose a mechanism for tumor growth emphasizing the role of homeostatic
regulation and tissue stability. We show that competition between surface and
bulk effects leads to the existence of a critical size that must be overcome by
metastases to reach macroscopic sizes. This property can qualitatively explain
the observed size distributions of metastases, while size-independent growth
rates cannot account for clinical and experimental data. In addition, it
potentially explains the observed preferential growth of metastases on tissue
surfaces and membranes such as the pleural and peritoneal layers, suggests a
mechanism underlying the seed and soil hypothesis introduced by Stephen Paget
in 1889 and yields realistic values for metastatic inefficiency. We propose a
number of key experiments to test these concepts. The homeostatic pressure as
introduced in this work could constitute a quantitative, experimentally
accessible measure for the metastatic potential of early malignant growths.Comment: 13 pages, 11 figures, to be published in the HFSP Journa
Simulating Reionization: Character and Observability
In recent years there has been considerable progress in our understanding of
the nature and properties of the reionization process. In particular, the
numerical simulations of this epoch have made a qualitative leap forward,
reaching sufficiently large scales to derive the characteristic scales of the
reionization process and thus allowing for realistic observational predictions.
Our group has recently performed the first such large-scale radiative transfer
simulations of reionization, run on top of state-of-the-art simulations of
early structure formation. This allowed us to make the first realistic
observational predictions about the Epoch of Reionization based on detailed
radiative transfer and structure formation simulations. We discuss the basic
features of reionization derived from our simulations and some recent results
on the observational implications for the high-redshift Ly-alpha sources.Comment: 3 pages, to appear in the Proceedings of First Stars III, Santa Fe,
July 2007, AIP Conference Serie
Occupationally related bilateral calcific tendonitis of Flexor carpi ulnaris: case report
We present a case of bilateral calcific tendonitis of the Flexor Carpi Ulnaris attributable to repetitive wrist action which was occupationally related. This was treated conservatively with avoidance of aggravating movement, resting splints and anti inflammatory medication when acute flare ups occurred. Since avoidance of repetitive strain on the wrists he has had no further flare ups in over 2 years. This is the only case of bilateral calcific tendonitis of Flexor Carpi Ulnaris that has been reported in the literature, further more it is the only one which has been attributed to occupation and settled following a change of career
Likelihood inference for exponential-trawl processes
Integer-valued trawl processes are a class of serially correlated, stationary
and infinitely divisible processes that Ole E. Barndorff-Nielsen has been
working on in recent years. In this Chapter, we provide the first analysis of
likelihood inference for trawl processes by focusing on the so-called
exponential-trawl process, which is also a continuous time hidden Markov
process with countable state space. The core ideas include prediction
decomposition, filtering and smoothing, complete-data analysis and EM
algorithm. These can be easily scaled up to adapt to more general trawl
processes but with increasing computation efforts.Comment: 29 pages, 6 figures, forthcoming in: "A Fascinating Journey through
Probability, Statistics and Applications: In Honour of Ole E.
Barndorff-Nielsen's 80th Birthday", Springer, New Yor
Defining critical factors in multi-country studies of assisted reproductive technologies (ART): data from the US and UK health systems
As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each otherâs limitations
Psychological impact of injuries sustained in motor vehicle crashes: Systematic review and meta-analysis
Objective: The aim of this meta-analysis was to determine the psychological impact associated with motor vehicle crash (MVC)-related physical injuries. Design: Systematic review and meta-analysis. Data sources: Multiple search engines included MEDLINE (via OVID), PsycINFO and Embase, and studies were sourced from scientific journals, conference papers and doctoral theses. Study selection: A high-yield search strategy was employed. Terms like 'psychological distress', 'depression', 'PTSD' and 'motor vehicle accident' were employed. These key words were run primarily and secondary searches were then conducted in association with the major injury types. Studies needed to compare psychological distress in people injured in an MVC with uninjured controls who had not recently experienced an MVC. Data extraction: Searches resulted in the identification of 2537 articles, and after eliminating duplicates and studies not meeting inclusion criteria, 24 studies were selected involving 4502 injured participants. These studies were entered into separate meta-analyses for mild to moderate traumatic brain injury (mTBI), whiplash-associated disorder (WAD) and spinal cord injury (SCI). Results: Elevated psychological distress was associated with MVC-related injuries with a large summary effect size in WAD (0.90), medium to large effect size in SCI (0.69) and small to medium effect size in mTBI (0.23). No studies meeting inclusion criteria were found for burns, fractures and low back injury. Increased psychological distress remains elevated in SCI, mTBI and WAD for at least 3 years post-MVC. Conclusions: Rehabilitation strategies are needed to minimise distress subsequent to MVC-related physical injuries and the scientific robustness of studies requires improvement
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