Prospects for studying how high-intensity compression waves cause damage in human blast injuries

Since World War I, explosions have accounted for over 70% of all injuries in conflict. With the development of improved personnel protection of the torso, improved medical care and faster aeromedical evacuation, casualties are surviving with more severe injuries to the extremities. Understanding the processes involved in the transfer of blast-induced shock waves through biological tissues is essential for supporting efforts aimed at mitigating and treating blast injury. Given the inherent heterogeneities in the human body, we argue that studying these processes demands a highly integrated approach requiring expertise in shock physics, biomechanics and fundamental biological processes. This multidisciplinary systems approach enables one to develop the experimental framework for investigating the material properties of human tissues that are subjected to high compression waves in blast conditions and the fundamental cellular processes altered by this type of stimuli. Ultimately, we hope to use the information gained from these studies in translational research aimed at developing improved protection for those at risk and improved clinical outcomes for those who have been injured from a blast wave.

Analysis of damage to buildings following the 2010–11 Eastern Australia floods

This research analyses the extent of damage to buildings in Brisbane, Ipswich and Grantham during the recent Eastern Australia flooding and explore the role planning and design/construction regulations played in these failures. It highlights weaknesses in the current systems and propose effective solutions to mitigate future damage and financial loss under current or future climates. 2010 and early 2011 saw major flooding throughout much of Eastern Australia. Queensland and Victoria were particularly hard hit, with insured losses in these states reaching $2.5 billion and many thousands of homes inundated. The Queensland cities of Brisbane and Ipswich were the worst affected; around two-thirds of all inundated property/buildings were in these two areas. Other local government areas to record high levels of inundation were Central Highlands and Rockhampton Regional Councils in Queensland, and Buloke, Campaspe, Central Gold Fields and Loddon in Victoria. Flash flooding was a problem in a number of Victorian councils, but the Lockyer Valley west of Ipswich suffered the most extensive damage with 19 lives lost and more than 100 homes completely destroyed. In all more than 28,000 properties were inundated in Queensland and around 2,500 buildings affected in Victoria. Of the residential properties affected in Brisbane, around 90% were in areas developed prior to the introduction of floodplain development controls, with many also suffering inundation during the 1974 floods. The project developed a predictive model for estimating flood loss and occupant displacement. This model can now be used for flood risk assessments or rapid assessment of impacts following a flood event.

Systematic differences in membrane acyl composition associated with varying body mass in mammals occur in all phospholipid classes : an analysis of kidney and brain

The acyl composition of membrane phospholipids in kidney and brain of mammals of different body mass was examined. It was hypothesized that reduction in unsaturation index (number of double bonds per 100 acyl chains) of membrane phospholipids with increasing body mass in mammals would be made-up of similar changes in acyl composition across all phospholipid classes and that phospholipid class distribution would be regulated and similar in the same tissues of the different-sized mammals. The results of this study supported both hypotheses. Differences in membrane phospholipid acyl composition (i. e. decreased omega-3 fats, increased monounsaturated fats and decreased unsaturation index with increasing body size) were not restricted to any specific phospholipid molecule or to any specific phospholipid class but were observed in all phospholipid classes. With increase in body mass of mammals both monounsaturates and use of less unsaturated polyunsaturates increases at the expense of the long-chain highly unsaturated omega-3 and omega-6 polyunsaturates, producing decreases in membrane unsaturation. The distribution of membrane phospholipid classes was essentially the same in the different-sized mammals with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) together constituting similar to 91% and similar to 88% of all phospholipids in kidney and brain, respectively. The lack of sphingomyelin in the mouse tissues and higher levels in larger mammals suggests an increased presence of membrane lipid rafts in larger mammals. The results of this study support the proposal that the physical properties of membranes are likely to be involved in changing metabolic rate.

Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice : real-time PCR quantitation

Orthotopic or intracardiac injection of human breast cancer cell lines into immunocompromised mice allows study of the molecular basis of breast cancer metastasis. We have established a quantitative real-time PCR approach to analyze metastatic spread of human breast cancer cells inoculated into nude mice via these routes. We employed MDA-MB-231 human breast cancer cells genetically tagged with a bacterial β-galactosidase (Lac-Z) retroviral vector, enabling their detection by TaqMan® real-time PCR. PCR detection was linear, specific, more sensitive than conventional PCR, and could be used to directly quantitate metastatic burden in bone and soft organs. Attesting to the sensitivity and specificity of the PCR detection strategy, as few as several hundred metastatic MDA-MB-231 cells were detectable in 100 μm segments of paraffin-embedded lung tissue, and only in samples adjacent to sections that scored positive by histological detection. Moreover, the measured real-time PCR metastatic burden in the bone environment (mouse hind-limbs, n = 48) displayed a high correlation to the degree of osteolytic damage observed by high resolution X-ray analysis (r2 = 0.972). Such a direct linear relationship to tumor burden and bone damage substantiates the so-called 'vicious cycle' hypothesis in which metastatic tumor cells promote the release of factors from the bone which continue to stimulate the tumor cells. The technique provides a useful tool for molecular and cellular analysis of human breast cancer metastasis to bone and soft organs, can easily be extended to other cell/marker/organ systems, and should also find application in preclinical assessment of anti-metastatic modalities.

Validity of accelerometry for measurement of activity in people with brain injury

Purpose To evaluate the validity of a uniaxial accelerometer (MTI Actigraph) for measuring physical activity in people with acquired brain injury (ABI) using portable indirect calorimetry (Cosmed K4b(2)) as a criterion measure. Methods Fourteen people with ABI and related gait pattern impairment (age 32 +/- 8 yr) wore an MTI Actigraph that measured activity (counts(.)min-(1)) and a Cosmed K4b(2) that measured oxygen consumption (mL(.)kg(-1.)min(-1)) during four activities: quiet sitting (QS) and comfortable paced (CP), brisk paced (BP), and fast paced (FP) walking. MET levels were predicted from Actigraph counts using a published equation and compared with Cosmed measures. Predicted METs for each of the 56 activity bouts (14 participants X 4 bouts) were classified (light, moderate, vigorous, or very vigorous intensity) and compared with Cosmed-based classifications. Results Repeated-measures ANOVA indicated that walking condition intensities were significantly different (P < 0.05) and the Actigraph detected the differences. Overall correlation between measured and predicted METs was positive, moderate, and significant (r = 0.74). Mean predicted METs were not significantly different from measured for CP and BP, but for FP walking, predicted METs were significantly less than measured (P < 0.05). The Actigraph correctly classified intensity for 76.8% of all activity bouts and 91.5% of light- and moderate-intensity bouts. Conclusions Actigraph counts provide a valid index of activity across the intensities investigated in this study. For light to moderate activity, Actigraph-based estimates of METs are acceptable for group-level analysis and are a valid means of classifying activity intensity. The Actigraph significantly underestimated higher intensity activity, although, in practice, this limitation will have minimal impact on activity measurement of most community-dwelling people with ABI.

International hermelin brain tumor symposium on matricellular proteins in normal and cancer cell-matrix interactions

The second of the Hermelin Brain Tumor Center Symposia was held once again at Henry Ford Hospital in Detroit, Michigan on October 24th and 25th, 2003. A public conference was held on the 24th while a closed-door session took place on the 25th. The purpose of these symposia is to bring together experts in a particular field of study with the aim to share information with each other and the public, but then to meet privately to present novel data, hold discussions, and share concepts. While the interaction is intended to benefit all involved, the incentive is the expectation that the shared information will aid researchers at the Hermelin Brain Tumor Center in their quest to identify potential therapeutic targets and explore translational therapeutic strategies for the treatment of patients suffering nervous system tumors...

Field validation of controlled Monte Carlo data generation for statistical damage identification employing Mahalanobis squared distance

This article presents the field applications and validations for the controlled Monte Carlo data generation scheme. This scheme was previously derived to assist the Mahalanobis squared distance–based damage identification method to cope with data-shortage problems which often cause inadequate data multinormality and unreliable identification outcome. To do so, real-vibration datasets from two actual civil engineering structures with such data (and identification) problems are selected as the test objects which are then shown to be in need of enhancement to consolidate their conditions. By utilizing the robust probability measures of the data condition indices in controlled Monte Carlo data generation and statistical sensitivity analysis of the Mahalanobis squared distance computational system, well-conditioned synthetic data generated by an optimal controlled Monte Carlo data generation configurations can be unbiasedly evaluated against those generated by other set-ups and against the original data. The analysis results reconfirm that controlled Monte Carlo data generation is able to overcome the shortage of observations, improve the data multinormality and enhance the reliability of the Mahalanobis squared distance–based damage identification method particularly with respect to false-positive errors. The results also highlight the dynamic structure of controlled Monte Carlo data generation that makes this scheme well adaptive to any type of input data with any (original) distributional condition.

Brain decoding based on functional magnetic resonance imaging using machine learning : a comparative study

Brain decoding of functional Magnetic Resonance Imaging data is a pattern analysis task that links brain activity patterns to the experimental conditions. Classifiers predict the neural states from the spatial and temporal pattern of brain activity extracted from multiple voxels in the functional images in a certain period of time. The prediction results offer insight into the nature of neural representations and cognitive mechanisms and the classification accuracy determines our confidence in understanding the relationship between brain activity and stimuli. In this paper, we compared the efficacy of three machine learning algorithms: neural network, support vector machines, and conditional random field to decode the visual stimuli or neural cognitive states from functional Magnetic Resonance data. Leave-one-out cross validation was performed to quantify the generalization accuracy of each algorithm on unseen data. The results indicated support vector machine and conditional random field have comparable performance and the potential of the latter is worthy of further investigation.

Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing

Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory

MicroRNAs are small non-coding RNAs that mediate post-transcriptional gene silencing. Fear-extinction learning in C57/Bl6J mice led to increased expression of the brain-specific microRNA miR-128b, which disrupted stability of several plasticity-related target genes and regulated formation of fear-extinction memory. Increased miR-128b activity may therefore facilitate the transition from retrieval of the original fear memory toward the formation of a new fear-extinction memory.