421 research outputs found
Study protocol for a prospective, longitudinal cohort study investigating the medical and psychosocial outcomes of UK combat casualties from the Afghanistan war: the ADVANCE Study.
INTRODUCTION: The Afghanistan war (2003-2014) was a unique period in military medicine. Many service personnel survived injuries of a severity that would have been fatal at any other time in history; the long-term health outcomes of such injuries are unknown. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) study aims to determine the long-term effects on both medical and psychosocial health of servicemen surviving this severe combat related trauma. METHODS AND ANALYSIS: ADVANCE is a prospective cohort study. 1200 Afghanistan-deployed male UK military personnel and veterans will be recruited and will be studied at 0, 3, 6, 10, 15 and 20 years. Half are personnel who sustained combat trauma; a comparison group of the same size has been frequency matched based on deployment to Afghanistan, age, sex, service, rank and role. Participants undergo a series of physical health tests and questionnaires through which information is collected on cardiovascular disease (CVD), CVD risk factors, musculoskeletal disease, mental health, functional and social outcomes, quality of life, employment and mortality. ETHICS AND DISSEMINATION: The ADVANCE Study has approval from the Ministry of Defence Research Ethics Committee (protocol no:357/PPE/12) agreed 15 January 2013. Its results will be disseminated through manuscripts in clinical/academic journals and presentations at professional conferences, and through participant and stakeholder communications. TRIAL REGISTRATION NUMBER: The ADVANCE Study is registered at ISRCTN ID: ISRCTN57285353
ADVANCE-TBI study protocol: traumatic brain injury outcomes in UK military personnel serving in Afghanistan between 2003 and 2014 - a longitudinal cohort study
INTRODUCTION: Outcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort. METHODS AND ANALYSIS: The ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3-5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions. ETHICS AND DISSEMINATION: The ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Ethics Committee (ref: 2126/MODREC/22). Findings will be disseminated via publications in peer-reviewed journals and presentations at conferences
Relationship between combat-related traumatic injury and ultrashort term heart rate variability in a UK military cohort: findings from the ADVANCE study
Introduction Combat-related traumatic injury (CRTI)
has been linked to an increased cardiovascular disease
(CVD) risk. The long-term impact of CRTI on heart rate
variability (HRV)—a robust CVD risk marker—has not
been explored. This study investigated the relationship
between CRTI, the mechanism of injury and injury severity
on HRV.
Methods This was an analysis of baseline data from
the ArmeD SerVices TrAuma and RehabilitatioN OutComE
(ADVANCE) prospective cohort study. The sample
consisted of UK servicemen with CRTI sustained during
deployment (Afghanistan, 2003–2014) and an uninjured
comparison group who were frequency matched to the
injured group based on age, rank, deployment period and
role in theatre. Root mean square of successive differences (RMSSD) was measured as a measure of ultrashort
term HRV via <16 s continuous recording of the femoral
arterial pulse waveform signal (Vicorder). Other measures
included injury severity (New Injury Severity Scores (NISS))
and injury mechanism.
Results Overall, 862 participants aged 33.9±5.4 years
were included, of whom 428 (49.6%) were injured and
434 (50.3%) were uninjured. The mean time from injury/
deployment to assessment was 7.91±2.05 years. The
median (IQR) NISS for those injured was 12 (6–27) with
blast being the predominant injury mechanism (76.8%).
The median (IQR) RMSSD was significantly lower in the
injured versus the uninjured (39.47 ms (27.77–59.77) vs
46.22 ms (31.14–67.84), p<0.001). Using multiple linear
regression (adjusting for age, rank, ethnicity and time from
injury), geometric mean ratio (GMR) was reported. CRTI
was associated with a 13% lower RMSSD versus the uninjured group (GMR 0.87, 95% CI 0.80–0.94, p<0.001).
A higher injury severity (NISS ≥25) (GMR 0.78, 95% CI
0.69–0.89, p<0.001) and blast injury (GMR 0.86, 95% CI
0.79–0.93, p<0.001) were also independently associated
with lower RMSSD.
Conclusion These results suggest an inverse association
between CRTI, higher severity and blast injury with HRV.
Longitudinal studies and examination of potential mediating factors in this CRTI-HRV relationship are needed
ADVANCE-TBI study protocol: traumatic brain injury outcomes in UK military personnel serving in Afghanistan between 2003 and 2014 - a longitudinal cohort study
INTRODUCTION: Outcomes of traumatic brain injury (TBI) are highly variable, with cognitive and psychiatric problems often present in survivors, including an increased dementia risk in the long term. Military personnel are at an increased occupational risk of TBI, with high rates of complex polytrauma including TBI characterising the UK campaign in Afghanistan. The ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE)-TBI substudy will describe the patterns, associations and long-term outcomes of TBI in the established ADVANCE cohort. METHODS AND ANALYSIS: The ADVANCE cohort comprises 579 military personnel exposed to major battlefield trauma requiring medical evacuation, and 566 matched military personnel without major trauma. TBI exposure has been captured at baseline using a standardised interview and registry data, and will be refined at first follow-up visit with the Ohio State Method TBI interview (a National Institute of Neurological Disorders and Stroke TBI common data element). Participants will undergo blood sampling, MRI and detailed neuropsychological assessment longitudinally as part of their follow-up visits every 3-5 years over a 20-year period. Biomarkers of injury, neuroinflammation and degeneration will be quantified in blood, and polygenic risk scores calculated for neurodegeneration. Age-matched healthy volunteers will be recruited as controls for MRI analyses. We will describe TBI exposure across the cohort, and consider any relationship with advanced biomarkers of injury and clinical outcomes including cognitive performance, neuropsychiatric symptom burden and function. The influence of genotype will be assessed. This research will explore the relationship between military head injury exposure and long-term outcomes, providing insights into underlying disease mechanisms and informing prevention interventions. ETHICS AND DISSEMINATION: The ADVANCE-TBI substudy has received a favourable opinion from the Ministry of Defence Research Ethics Committee (ref: 2126/MODREC/22). Findings will be disseminated via publications in peer-reviewed journals and presentations at conferences
Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions
We report on a search for metastable positively and negatively charged states
of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864.
We have sampled approximately six billion 10% most central Au+Pb interactions
and have observed no strangelet states (baryon number A < 100 droplets of
strange quark matter). We thus set upper limits on the production of these
exotic states at the level of 1-6 x 10^{-8} per central collision. These limits
are the best and most model independent for this colliding system. We discuss
the implications of our results on strangelet production mechanisms, and also
on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover
memorial edition
Design and function of superfast muscles : new insights into the physiology of skeletal muscle
First published online as a Review in Advance on October 24, 2005. (Some corrections may occur before final publication online and in print)Author Posting. © Annual Reviews, 2005. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Physiology 68 (2006): 22.1-22.29, doi:10.1146/annurev.physiol.68.040104.105418.Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.This work was made possible by support from NIH grants AR38404 and AR46125
as well as the University of Pennsylvania Research Foundation
Attenuation of microvascular function in those with cardiovascular disease is similar in patients of Indian Asian and European descent
addresses: Institute of Biomedical and Clinical Science, Peninsula Medical School (Exeter), University of Exeter, UK. [email protected]: PMCID: PMC2823616types: Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't© 2010 Strain et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Indian Asians are at increased risk of cardiovascular death which does not appear to be explained by conventional risk factors. As microvascular disease is also more prevalent in Indian Asians, and as it is thought to play a role in the development of macrovascular disease, we decided to determine whether impaired microcirculation could contribute to this increased cardiovascular risk in Indian Asians
Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution
During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit
The genomes of two key bumblebee species with primitive eusocial organization
Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation
Optimization of a Low Cost and Broadly Sensitive Genotyping Assay for HIV-1 Drug Resistance Surveillance and Monitoring in Resource-Limited Settings
Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX
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