Awareness of social care needs in people with epilepsy and intellectual disability.

BACKGROUND: Nearly a quarter of people with intellectual disability (ID) have epilepsy with large numbers experiencing drug-resistant epilepsy, and premature mortality. To mitigate epilepsy risks the environment and social care needs, particularly in professional care settings, need to be met. PURPOSE: To compare professional care groups as regards their subjective confidence and perceived responsibility when managing the need of people with ID and epilepsy. METHOD: A multi-agency expert panel developed a questionnaire with embedded case vignettes with quantitative and qualitative elements to understand training and confidence in the health and social determinants of people with ID and epilepsy. The cross-sectional survey was disseminated amongst health and social care professionals working with people with ID in the UK using an exponential non-discriminative snow-balling methodology. Group comparisons were undertaken using suitable statistical tests including Fisher's exact, Kruskal-Wallis, and Mann-Whitney. Bonferroni correction was applied to significant (p < 0.05) results. Content analysis was conducted and relevant categories and themes were identified. RESULTS: Social and health professionals (n = 54) rated their confidence to manage the needs of people with ID and epilepsy equally. Health professionals showed better awareness (p < 0.001) of the findings/recommendations of the latest evidence on premature deaths and identifying and managing epilepsy-related risks, including the relevance of nocturnal monitoring. The content analysis highlighted the need for clearer roles, improved care pathways, better epilepsy-specific knowledge, increased resources, and better multi-disciplinary work. CONCLUSIONS: A gap exists between health and social care professionals in awareness of epilepsy needs for people with ID, requiring essential training and national pathways.

Death from drought in tropical forests is triggered by hydraulics not carbon starvation.

Drought threatens tropical rainforests over seasonal to decadal timescales, but the drivers of tree mortality following drought remain poorly understood. It has been suggested that reduced availability of non-structural carbohydrates (NSC) critically increases mortality risk through insufficient carbon supply to metabolism ('carbon starvation'). However, little is known about how NSC stores are affected by drought, especially over the long term, and whether they are more important than hydraulic processes in determining drought-induced mortality. Using data from the world's longest-running experimental drought study in tropical rainforest (in the Brazilian Amazon), we test whether carbon starvation or deterioration of the water-conducting pathways from soil to leaf trigger tree mortality. Biomass loss from mortality in the experimentally droughted forest increased substantially after >10 years of reduced soil moisture availability. The mortality signal was dominated by the death of large trees, which were at a much greater risk of hydraulic deterioration than smaller trees. However, we find no evidence that the droughted trees suffered carbon starvation, as their NSC concentrations were similar to those of non-droughted trees, and growth rates did not decline in either living or dying trees. Our results indicate that hydraulics, rather than carbon starvation, triggers tree death from drought in tropical rainforest.

The impact of an epilepsy nurse competency framework on the costs of supporting adults with epilepsy and intellectual disability: findings from the EpAID study.

BACKGROUND: The development of a nurse-led approach to managing epilepsy in adults with an intellectual disability (ID) offers the potential of improved outcomes and lower costs of care. We undertook a cluster randomised trial to assess the impact on costs and outcomes of the provision of ID nurses working to a designated epilepsy nurse competency framework. Here, we report the impact of the intervention on costs. METHOD: Across the United Kingdom, eight sites randomly allocated to the intervention recruited 184 participants and nine sites allocated to treatment as usual recruited 128 participants. Cost and outcome data were collected mainly by telephone interview at baseline and after 6 months. Total costs at 6 months were compared from the perspective of health and social services and society, with adjustments for pre-specified participant and cluster characteristics at baseline including costs. Missing data were imputed using multiple imputation. Uncertainty was quantified by bootstrapping. RESULTS: The intervention was associated with lower per participant costs from a health and social services perspective of -£357 (2014/2015 GBP) (95% confidence interval -£986, £294) and from a societal perspective of -£631 (95% confidence interval -£1473, £181). Results were not sensitive to the exclusion of accommodation costs. CONCLUSIONS: Our findings suggest that the competency framework is unlikely to increase the cost of caring for people with epilepsy and ID and may reduce costs.

Effect of ageing on the calibration of ballistic gelatin.

PURPOSE: Ballistic gelatin is commonly used as a validated surrogate for soft tissue during terminal ballistic testing. However, the effect of a delay between production and testing of a gelatin mould remains unknown. The aim of this study was to determine any potential effects of ageing on ballistic gelatin. METHODS: Depth of penetration (DoP) of 4.5 mm spherical fragment simulating projectiles was ascertained using mixtures of 10%, 11.25% and 20% Type A 250 Bloom ballistic gelatin. Testing was performed daily for 5 days using velocities between 75 and 210 m/s. DoP at day 5 was statistically compared with day 1, and net mass change was recorded daily. RESULTS: No significant difference was found for DoP observed with time in any of the samples (P>0.05). Spearman correlation was excellent in all moulds. The moulds with known standard calibrations remained in calibration throughout the study period. Mass loss of less than 1% was noted in all samples. CONCLUSION: Mass loss was the only quantifiable measure of changes in the blocks with time, but did not correlate with any changes in DoP. This may provide reassurance when undertaking such testing that an inadvertent delay will not significantly alter the penetration properties of the mould. Future research is recommended to determine any potential effect on the mechanical properties of gelatin at higher velocity impacts and whether the calibration corresponds to an adequate simulation under such conditions.

Influence of rib impact on thoracic gunshot trauma.

INTRODUCTION: The influence of rib impact on thoracic gunshot trauma remains unclear, despite its high occurrence. This study therefore investigates the effect of rib impact on a bullet's terminal properties and injury severity. METHODS: Two bullets were used: 5.56×45 mm (full charge and reduced charge) and 7.62×51 mm (full charge). For each bullet, three impact groups were tested: (1) plain 10% ballistic gelatin (control) conditioned at 4°C, (2) intercostal impact, and (3) rib impact, the latter two tested with samples of porcine thoracic walls embedded in gelatin. Analysis included penetration depth, trajectory change, yaw, fragmentation, velocity reduction, energy deposition and temporary and permanent cavity characteristics. RESULTS: No significant differences were observed for most variables. Differences were found between rib (and intercostal) impact and the control groups, suggesting that the inclusion of thoracic walls produces an effect more significant than the anatomical impact site. Effects were ammunition specific. For the 7.62×51 mm round, rib impact caused an earlier onset of yaw and more superficial permanent gelatin damage compared with plain gelatin. This round also formed a larger temporary cavity on rib impact than intercostal impact. Rib (and intercostal impact) created a smaller temporary cavity than the control for the 5.56×45 mm round. For the reduced-charge 5.56×45 mm round, rib and intercostal impact produced greater velocity reduction compared with plain gelatin. CONCLUSIONS: This study provides new insights into the role of rib impact in thoracic gunshot injuries, and indicates that the effects are ammunition dependent. Unlike the 5.56×45 mm rounds, rib impact with the 7.62×51 mm rounds increases the risk of severe wounding.

The incidence and prevalence of epilepsy in the United Kingdom 2013-2018: A retrospective cohort study of UK primary care data.

PURPOSE: The aim of this study was to update overall incidence and prevalence calculations for epilepsy of the United Kingdom (UK) and its constituent nations (England, Northern Ireland, Scotland, and Wales). METHODS: We used data from primary care practices contributing to the Clinical Practice Research Datalink (CRPD), based on the electronic health records of 14 million patients, representing approximately 20% of the population. CPRD contains data from two different health record systems: the Vision clinical system (CPRD GOLD database) and the EMIS Web® clinical system (CPRD Aurum database). We calculated incidence and prevalence rates with 95% confidence intervals (CIs). Data were stratified by age, gender, deprivation, country (England, Scotland, Wales and Northern Ireland) and region (England only). RESULTS: In the UK, the estimated overall point prevalence for epilepsy was 9.37 per 1000 persons / year (95% CI 9.34-9.40) and the overall estimated incidence rate was 42.68 per 100,000 person-years (95% 42.18-43.18) using the CPRD GOLD database. In England, the estimated incidence (37.41 (95% CI 36.96-37.83)) and prevalence (8.85 (95% CI 8.83-8.87)) was lower (combined databases) compared to figures for Scotland (incidence 47.76 (95% CI 46.15-49.42)); prevalence 10.13 (95% CI 10.06-10.20)) (CPRD GOLD only), Wales (incidence 54.84 (95% CI 52.79-56.95); prevalence 11.40 (95% CI 11.31-11.49)) (CPRD GOLD only) and Northern Ireland (incidence 46.18 (95% CI 43.13-49.90); prevalence 12.08 (95% CI 11.93-12.23))(combined databases). Prevalence and incidence were higher in more deprived regions. CONCLUSION: The prevalence and incidence of epilepsy in the UK is broadly in line with other high income countries, showing the usual pattern of high incidence in the young and the old, with a nadir in middle age. The prevalence of epilepsy has fallen slightly since 2011. There is significant geographical variation (between countries and between regions), and a suggestion of a relationship between deprivation and epilepsy which needs further investigation.

Viability of Bos taurus scapulae as a flat bone proxy for ballistic testing.

BACKGROUND: Handguns and rifles are often involved in violent deaths such as homicide and suicide. Consequently, forensic investigations are important to clarify the nature of ballistic trauma. METHODS: This study investigated the differences in entrance and exit wound morphology with Bos taurus (bovine) scapulae that have two cortical layers surrounding a central cancellous bone section which are comparable with human flat bones, with a series of experiments using six different calibres (0.22 Long Rifle, 9×19 mm North Atlantic Treaty Organization, 0.40 Smith & Wesson, 0.45 Automatic Colt Pistol, 5.56×45 mm and 7.62×51 mm). B. taurus (bovine) scapulae were used for closed range 30 cm simulated executions. RESULTS: The ballistic experiments presented similarities in entrance wound morphology and exit wound bevelling with that of recognised forensic cases. As muzzle velocity increased, bevelling increased. Circumferential delamination is clearly visible with full metal jacket rounds, yielding similar bone damage morphology as human crania. CONCLUSION: Bovine scapulae seem appropriate for ballistic simulations of flat bone injuries on the macroscopic level, if the correct portion of the scapulae is deployed. More research is needed to further substantiate these interpretations.

Microscopic and macroscopic comparisons of 0.223 soft point and full metal jacket ammunition with bos taurus scapulae as a proxy to human flat bones.

BACKGROUND: The prevalence of civilian 0.223 ammunition is widespread. Due to low costs and the same dimensions as a 5.56×45 mm North Atlantic Treaty Organization, this round is exceptionally popular. However, recent mass shootings have employed soft point (SP) expanding ammunition to cause grievous wounds compared with military full metal jacket (FMJ) rounds that do not rapidly expand on impact. METHODS: The aim of this given study is to compare FMJ and SP rounds to determine if there are diagnostic differences between the bullet types in the wounds inflicted to flat bones. Bos taurus scapulae were used for 25 m simulated cranial gunshot injuries. Scanning electron microscopy was employed to assess the difference in wound morphology and elemental analysis between SP and FMJ rounds. RESULTS: Entrance and exit wound morphology change significantly between the two different types of ammunition as seen with circumferential delamination which is indicative of FMJ rounds and is not seen with the softer SP hunting rounds. Lead staining of the entrance wound is visible on only the SP rounds. CONCLUSION: Gunshot flat bone wound morphology is distinctively different between SP and FMJ rounds. Circumferential delamination is only seen with FMJ due to the hardness of the round. Lead staining is only seen with SP rounds due to bullet composition.

The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens.

Mice expressing the minor lymphocyte stimulation antigens, Mls-1a, -2a, or -3a, singly on the B10.BR background have been generated. Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome. The open reading frames within the 3' long terminal repeats of the integrated MTVs 1, 3, 6, and 13 encode V beta 3-specific superantigens. Sequence data for these viral superantigens is presented, indicating that it is the COOH-terminal portion of the viral superantigen that interacts with the T cell receptor V beta element.

The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire.

Most laboratory strains of mice have between two and eight endogenous superantigens. These viral superantigens (vSAGs) are coded by genes in the 3' long terminal repeats of endogenous mammary tumor viruses (Mtv's). A line of Mtv-negative mice and several lines of mice containing single Mtv's were created by inbreeding the F2 progeny of CBA/CaJ and C58/J mice, which have no Mtv integrants in common. This allowed the T cell repertoire of H-2k mice, unaffected by Mtv superantigens, as well as the effects of vSAGs upon that repertoire, to be studied. Although each individual mouse had a different mix of C58/J and CBA/CaJ background genes, the T cell repertoires of different Mtv-negative mice were very similar and were reproducible. Since the background genes did not affect the V beta repertoire, there are no super-antigens, other than those encoded by Mtv's, that differ between CBA/CaJ and C58/J. CD4 and CD8 T cells had quite different repertoires in the Mtv-negative mice because of the effects of class I and class II major histocompatibility complex molecules on positive and negative selection. vSAG3 was found to delete V beta 5 T cells, while vSAG8 deleted V beta 7 T cells, and vSAG9 deleted V beta 13 T cells in addition to their previously reported specificities. vSAG17 deletes a small proportion of CD4+ T cells bearing V beta 11 and -12. vSAG14 and -30 have little effect on the T cell repertoire and are not expressed in thymocytes and splenocytes. An endogenous superantigen that has a low avidity for a particular V beta may positively select thymocytes, leading to an increased frequency of peripheral T cells bearing the relevant V beta s. We found evidence that vSAG11 may positively select T cells bearing V beta 8.2. Our data, which analyzed the effects of seven endogenous Mtv's, showed little evidence of positive selection by any other vSAGs on T cells bearing any V beta tested, despite published reports to the contrary.

Antigen recognition properties of mutant V beta 3+ T cell receptors are consistent with an immunoglobulin-like structure for the receptor.

We examined the effect of mutations in the V beta portion of a pigeon cytochrome c (cyto c)-specific V beta 3+/V alpha 11+ T cell receptor on its ability to recognize cyto c/IEk and various superantigens. The results were consistent with an immunoglobulin-like structure for the receptor V beta domain and with separate interaction sites on V beta for conventional antigen and superantigens. An amino acid predicted to lie in CDR1 was critical for cyto c/IEk but not superantigen recognition, while several amino acids predicted to lie in the hypervariable region 4 loop were critical for superantigen but not cyto c/IEk recognition.

Surprisingly uneven distribution of the T cell receptor V beta repertoire in wild mice.

We have examined TCR V beta expression in a collection of wild mice. Many of the mice were homozygous for a large deletion at the V beta locus, and many animals also suppressed expression of several V betas using self superantigens. Expression of V beta 8.2 was unexpectedly suppressed by a self superantigen in some wild mice, which was due to the presence in these animals of a variant V beta 8.2 gene. The amino acid changes in this gene product suggest contact sites between V beta and the superantigen. Although all V betas are expressed within each wild mouse population, individual mice have a limited and variable V beta repertoire. The independent origin of multiple V beta deletions and the presence of polymorphic self superantigens suggest that this variation may be maintained by balancing selection.

Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta.

Superantigen bound to major histocompatibility complex (MHC) products have been shown to stimulate T cells in a V beta-specific manner. Mouse T cells bearing V beta 8.1 usually respond to the self superantigen, Mls-1a, whereas T cells bearing V beta 8.2a do not. Previously, using site-directed mutational analysis, we identified the residues of natural variants of T cell receptor (TCR) V beta 8.2 that conferred Mls-1a reactivity. These residues are predicted to lie on a beta-pleated sheet of the TCR V beta element, well away from the expected binding site for antigen and MHC proteins. This study was undertaken to determine the effect of glycosylation on this beta-pleated sheet on Mls-1a reactivity and to map the extent of the interaction site on V beta 8.2 for Mls-1a. to Mls-1a, as well as to peptides derived from the conventional protein antigen, chicken ovalbumin. Here we demonstrate that first, N-linked carbohydrate on the lateral surface of V beta blocks the interaction of the TCR V beta with the self superantigen, Mls-1a, but has no effect on the TCR interaction with peptide antigen and MHC, second, that the interaction site for Mls-1a extends over the surface of the solvent-exposed beta-pleated sheet on the side of the TCR, and third, that mutations which affect both superantigen and peptide antigen reactivity lie at the beginning of the first complementarity determining region of V beta, consistent with models of the trimolecular complex of TCR-peptide-MHC.

Increase in presynaptic territory of C-terminals on lumbar motoneurons of G93A SOD1 mice during disease progression.

Compensatory synaptic plasticity is reported in muscle and the central nervous system of motor neuron disease patients, and transgenic SOD1 mice, but direct ultrastructural evidence for spinal motoneurons is lacking. Prompted by our observation in spinal cords from autopsied patients suggesting selective enlargement of the ultrastructurally distinctive C-type terminal synapsing with spinal motoneurons, we examined the ultrastructural synaptology of lumbar motoneurons during disease progression in age- and sex-matched wild-type mice, transgenic G93A SOD1 mice, and mice overexpressing normal human SOD1 (Wt(SOD1)). Prescribed criteria classified presynaptic terminals of motoneurons into five ultrastructural classes (S, F, T, M, and C). Computerized morphometry on electronmicrographs was used to measure their appositional lengths, coverage of the motoneuron membrane, and sizes of postsynaptic structures. No terminal degeneration occurred in wild-type or Wt(SOD1) mice. In transgenic mice, degeneration of motoneurons and S-terminals and F-terminals commenced presymptomatically (10 weeks), and continued into the symptomatic stage (18 weeks). However, C-terminals were preserved. Morphometry confirmed significant reductions in frequency and membrane coverage for S-terminals and F-terminals between 10 and 18 weeks, but a maintained frequency of C-terminals coupled with increased appositional length and coverage of the motoneuron membrane. Increased C-terminal size was matched by growth of its characterizing postsynaptic cistern and Nissl body. The results reveal selective preservation and increased presynaptic territory of the C-type terminal. As C-terminals derive from cholinergic intrasegmental propriospinal interneurons and may modulate motoneuron excitability, their increased presynaptic territory on surviving motoneurons of transgenic SOD1 mice may represent a means of maintaining excitability, compensating for the loss of overall presynaptic input.

Full deflection profile calculation and Young's modulus optimisation for engineered high performance materials.

New engineered materials have critical applications in different fields in medicine, engineering and technology but their enhanced mechanical performances are significantly affected by the microstructural design and the sintering process used in their manufacture. This work introduces (i) a methodology for the calculation of the full deflection profile from video recordings of bending tests, (ii) an optimisation algorithm for the characterisation of Young's modulus, (iii) a quantification of the effects of optical distortions and (iv) a comparison with other standard tests. The results presented in this paper show the capabilities of this procedure to evaluate the Young's modulus of highly stiff materials with greater accuracy than previously possible with bending tests, by employing all the available information from the video recording of the tests. This methodology extends to this class of materials the possibility to evaluate both the elastic modulus and the tensile strength with a single mechanical test, without the need for other experimental tools.

Resilience of the Asian atmospheric circulation shown by Paleogene dust provenance.

The onset of modern central Asian atmospheric circulation is traditionally linked to the interplay of surface uplift of the Mongolian and Tibetan-Himalayan orogens, retreat of the Paratethys sea from central Asia and Cenozoic global cooling. Although the role of these players has not yet been unravelled, the vast dust deposits of central China support the presence of arid conditions and modern atmospheric pathways for the last 25 million years (Myr). Here, we present provenance data from older (42-33 Myr) dust deposits, at a time when the Tibetan Plateau was less developed, the Paratethys sea still present in central Asia and atmospheric pCO2 much higher. Our results show that dust sources and near-surface atmospheric circulation have changed little since at least 42 Myr. Our findings indicate that the locus of central Asian high pressures and concurrent aridity is a resilient feature only modulated by mountain building, global cooling and sea retreat.

The pro and the active form of matrix metalloproteinase-9 is increased in serum of patients with amyotrophic lateral sclerosis.

Pro and active-matrix metalloproteinase-9 (MMP-9) was measured in sera from patients with amyotrophic lateral sclerosis (ALS), Guillain-Barre syndome (GBS), and healthy subjects. Both forms of MMP-9 were elevated in sera of ALS and GBS patients, compared with healthy controls. It has been postulated that elevated MMP-9 reflects damage to peripheral nerve and muscle. This possibility was investigated in sera, and tissue extracts of sciatic nerves and muscle from mice 5 and 12 days after axotomy of the sciatic nerve. Pro-MMP-9 was elevated in sera and extracts of damaged nerve and muscle, suggesting such damage may be followed by elevated pro-MM9-9 in sera. Active MMP-9 was only elevated in the sera. However, in situ activation of MMP-9 is tightly regulated and localised, and probably difficult to demonstrate by ELISA, resulting in a short half-life active MMP-9, implying any active MMP-9 in the serum may have a more immediate origin than injured muscle or nerve, for example circulating blood cells.

The effects of altered distances between obstacles on the jump kinematics and apparent joint angulations of large agility dogs.

Canine agility is a rapidly growing sport in the UK. However, there is a paucity of scientific research examining jump kinematics and associated health and welfare implications of the discipline. The aim of this research was to examine differences in jump kinematics and apparent joint angulation of large (>431 mm at the withers) agility dogs (n = 54), when the distance between hurdles was altered (3.6 m, 4 m and 5 m apart) and to determine how level of skill impacted upon jump kinematics. Significant differences were observed for both the take-off (P <0.001) and landing distances (P <0.001) between the 3.6 m, 4 m and 5 m distances. Further differences were observed when level of skill was controlled for; take-off (F[3,55] = 5.686, P = 0.002) and landing (F[3,55] = 7.552, P <0.001) distances differed at the 3.6 m distance, as did the take-off distance at the 4 m hurdle distance (F[3,50] = 6.168, P = 0.001). Take-off and landing speeds differed for hurdle distances (P <0.001) and level of skill (P <0.001). There were significant differences in apparent neck angle during take-off and landing (P <0.001), lumbar spine angles during take-off, bascule and landing (P <0.01), and in shoulder angles during the bascule phase (P <0.05). The results indicate that agility dogs alter their jumping patterns to accommodate the spacing between hurdles, which ultimately may impact long term health and welfare due to altered kinematics.

Citrate synthase: an immunochemical investigation of interspecies diversity.

Rabbit antibodies have been raised to pig heart citrate synthase. Using purified IgG, competitive enzyme-linked immunoassays and assays of citrate synthase activity indicate the presence of antibodies to a number of antigenic sites on the enzyme, only some of which are essential for catalytic activity. From a comparison of citrate synthases from prokaryotic and eukaryotic organisms, the degree of interaction between antibody and enzyme was in the order: pig heart greater than pigeon breast greater than Bacillus megaterium greater than Escherichia coli. These findings are discussed in terms of the known interspecies diversity of the enzyme.

Quantitative synaptology of feline motoneurones to external anal sphincter muscle.

Motoneurones innervating the cat external anal sphincter muscle were labelled retrogradely following intramuscular injections with horseradish peroxidase (HRP). Labelled motoneurones were examined by correlative light and electron microscopy (LM and EM) with special regard to a qualitative and morphometric analysis of the axon terminals resident on the neuronal membrane. By LM, labelled motoneurones were (1) ipsilateral to the injections; (2) all in S1-S2; (3) found only in the superior dorsomedial region of Onuf's nucleus; and (4) exhibited a broad spectrum of diameters (25-72 micron, mean 47.4 +/- 11.3 micron). By EM, axon terminals on the neuronal membrane when classified according to size, vesicle shape, and synaptic complex ultrastructure conformed to the S-, F-, T-, M-, and C-type terminals previously described for cat lumbosacral motoneurones. C-terminals confirmed these sphincteric motoneurones to be skeletomotor. Pooled data from midnuclear sections through 15 random labelled motoneurones (20-64-micron diameter) revealed that S- and F-type terminals predominated, with numerically few M and C types. Notwithstanding their low frequency (0.3/100 micron membrane) C-terminals contributed 1% of the mean areal coverage by terminals, which implies a potentially larger synaptic influence relative to other terminal types. Linear relationships occurred between terminal frequency (or cover) and motoneurone diameter. While motoneurones greater than 40 micron in diameter exhibited all five terminal types, labelled motoneurones less than or equal to 30 micron generally possessed only S-, F-, and occasional T-type terminals, and in this respect resembled gamma motoneurones.