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 other’s 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