Early exposure to environmental toxin contributes to neuronal vulnerability and axonal pathology in a model of familial ALS

Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of parkinsonism and dementia in some patients led to searches for an environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease

A reduced-order thermomechanical model and analytical solution for uniaxial shape memory alloy wire actuators

A lumped shape memory alloy (SMA) model is derived from the thermodynamic model of Chang et al (2006 Contin. Mech. Thermodyn. 18 83 118), using a set of simplifying assumptions, that reduces the system of partial differential equations for an SMA/bias spring actuator to a nonlinear, first-order, ordinary differential equation. Dimensionless state variables and parameters are defined that are useful for characterizing the actuator system and for studying its performance and scaling. A general analytical solution to the nonlinear differential equation governing phase transformation is found in terms of the Lambert function for a piecewise constant Joule heating input and a constant temperature convective environment. The analytical solution provides a useful and convenient tool for assessing the time-dependent, hysteretic response of this simple class of SMA actuators, with which design and optimization studies are performed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65088/2/sms9_6_065001.pd

Pre-hospital pain management by ambulance staff

BACKGROUND In the 2004 Healthcare Commission report the majority of patients (4 out of 5) said they had suffered pain from their presenting conditions while in the ambulance. Although 81% felt that the ambulance crew did everything they could to control pain, 1 in 5 wanted more pain relief: 14% said the crew did this to some extent and 5% that the crew did not do everything they could to control the pain. The management of pain in the pre-hospital environment has been shown to be an important determinant of subsequent pain in the emergency department. How ambulance services manage pain is therefore clinically important and a key indicator of quality of service. Management of pain can be differentiated into a number of essential components. Recording of pain both at the scene (either the patient's home or the scene of an emergency) and on arrival at hospital has been shown to be feasible using numerical, verbal 1 and visual analogue scales 2 . Recording pain scores is valuable, not only because it is a simple method of assessing pain, but because it has been shown to increase the likelihood of administration of analgesia and facilitates an estimation of the effectiveness of treatment. 3 In one study, a reduction in pain score of at least 20mm out of 100mm on a visual analogue scale corresponded to a clinically meaningful reduction in the level of pain reported by patients experiencing acute pain 4 . The type, dose, route 5;6 and timeliness 7 of analgesia are important determinants of the effectiveness of pain relief. Strong analgesics including opiates have been available for use by paramedics for the management of pain since the early 1990s.. The feasibility of pain assessment in the prehospital setting. Prehosp.Emerg.Care 2004;8:155-61. 2 Lord BA,.Parsell B. Measurement of pain in the prehospital setting using a visual analogue scale. Prehospital.Disaster.Med. 2003;18:353-8. 3 Silka PA, Roth MM, Moreno G, Merrill L, Geiderman JM, Pain scores improve analgesic administration patterns for trauma patients in the emergency department. Acad.Emerg.Med. 2004;11:264-70. 4 Kelly AM. Setting the benchmark for research in the management of acute pain in emergency departments. Emerg.Med.(Fremantle.) 2001;13:57-60. 5 Woollard M, Jones T, Pitt K, Vetter N. Hitting them where it hurts? Low dose nalbuphine therapy. Emerg.Med.J. et al. Less IS less: a randomised controlled trial comparing cautious and rapid nalbuphine dosing regimens. Emerg.Med.J. 2004;21:362-4. 7 Karlson BW, Sjolin M, Herlitz J. Clinical factors associated with pain in acute myocardial infarction. Cardiology 1993;83:107-17. RESEARCH AIMS The aim of the study is to examine whether factors such age, sex, condition of the patient, and distance from hospital etc affect decisions to assess pain and/or administer analgesia

Particle dynamics of a cartoon dune

The spatio-temporal evolution of a downsized model for a desert dune is observed experimentally in a narrow water flow channel. A particle tracking method reveals that the migration speed of the model dune is one order of magnitude smaller than that of individual grains. In particular, the erosion rate consists of comparable contributions from creeping (low energy) and saltating (high energy) particles. The saltation flow rate is slightly larger, whereas the number of saltating particles is one order of magnitude lower than that of the creeping ones. The velocity field of the saltating particles is comparable to the velocity field of the driving fluid. It can be observed that the spatial profile of the shear stress reaches its maximum value upstream of the crest, while its minimum lies at the downstream foot of the dune. The particle tracking method reveals that the deposition of entrained particles occurs primarily in the region between these two extrema of the shear stress. Moreover, it is demonstrated that the initial triangular heap evolves to a steady state with constant mass, shape, velocity, and packing fraction after one turnover time has elapsed. Within that time the mean distance between particles initially in contact reaches a value of approximately one quarter of the dune basis length

Shape memory alloy honeycombs: experiments & simulation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76238/1/AIAA-2007-1739-156.pd

IFN-γ-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain.

It is well established that IFN-γ is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN-γ during P. berghei ANKA infection have not been investigated, and it is not known whether IFN-γ production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN-γ reporter mice, we show that NK cells dominate the IFN-γ response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4(+) and CD8(+) T cells. Importantly, we demonstrate that IFN-γ-producing CD4(+) T cells, but not innate or CD8(+) T cells, can promote the development of ECM in normally resistant IFN-γ(-/-) mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4(+) T cells accumulate within the spleen, lung, and brain of IFN-γ(-/-) mice and induce ECM through active IFN-γ secretion, which increases the accumulation of endogenous IFN-γ(-/-) CD8(+) T cells within the brain. Depletion of endogenous IFN-γ(-/-) CD8(+) T cells abrogates the ability of wild-type CD4(+) T cells to promote ECM. Finally, we show that IFN-γ production, specifically by CD4(+) T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8(+) T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-γ-producing CD4(+) T cells promote the development of ECM during P. berghei ANKA infection

Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis?

Objectives: To conduct a geographically defined, UK-based case-control study, to examine any association between physical activity (PA) and amyotrophic lateral sclerosis (ALS). Methods: A novel historical PA questionnaire was designed, validated, and subsequently administered in individual face-to-face interviews of 175 newly diagnosed sporadic ALS cases and 317 age- and sex-matched community controls. Historical PA energy expenditure and time spent in vigorous-intensity PA were derived from questionnaire data and compared between cases and controls. Results: Participation in an extra 10kJ/kg/day of PA (equivalent to approximately 45minutes brisk walking) was consistently associated with an increased risk of ALS, with the strongest association observed for adulthood exercise-related PA (OR 1.47, 95% CI 1.10-1.97). An extra 10mins/day of vigorous PA was also associated with the odds of ALS (OR 1.03, 95% CI 1·01-1·05). Results were slightly attenuated following adjustment for smoking and educational attainment. Conclusions: To our knowledge this is the first study to demonstrate a positive association between ALS and PA participation using a specifically designed and validated historical PA questionnaire. Despite the well-established health benefits of PA, a high activity lifestyle may also be associated with elevated risk of ALS. Large-scale prospective studies in the future may help to confirm this association.This study was funded by a Medical Research Council/Motor Neurone Disease Association Lady Edith Wolfson Fellowship.This is the final version of the article. It first appeared from Taylor and Francis via https://doi.org/10.3109/21678421.2016.115457