Tantalum oxide and silicon oxide mixture coatings deposited using microwave plasma assisted co-sputtering for optical mirror coatings in gravitational wave detectors.

This work presents the characterization of the optical and mechanical properties of thin films based on (T a 2 O 5)1-x (S i O 2)x mixed oxides deposited by microwave plasma assisted co-sputtering, including post-annealing treatments. The deposition of low mechanical loss materials (3×10-5) with a high refractive index (1.93) while maintaining low processing costs was achieved and the following trends were demonstrated: The energy band gap increased as the S i O 2 concentration was increased in the mixture, and the disorder constant decreased when the annealing temperatures increased. Annealing of the mixtures also showed positive effects to reduce the mechanical losses and the optical absorption. This demonstrates their potential as an alternative high-index material for optical coatings in gravitational wave detectors using a low-cost process.

Amorphous dielectric optical coatings deposited by plasma ion-assisted electron beam evaporation for gravitational wave detectors.

Coating thermal noise (CTN) in amorphous coatings is a drawback hindering their application in precision experiments such as gravitational wave detectors (GWDs). Mirrors for GWDs are Bragg's reflectors consisting of a bilayer-based stack of high- and low-refractive-index materials showing high reflectivity and low CTN. In this paper, we report the characterization of morphological, structural, optical, and mechanical properties of high-index materials such as scandium sesquioxide and hafnium dioxide and a low-index material such as magnesium fluoride deposited by plasma ion-assisted electron beam evaporation. We also evaluate their properties under different annealing treatments and discuss their potential for GWDs.

Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial.

Importance: Bleeding is the most common cause of preventable death after trauma. Objective: To determine the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) when used in the emergency department along with standard care vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage. Design, Setting, and Participants: Pragmatic, bayesian, randomized clinical trial conducted at 16 major trauma centers in the UK. Patients aged 16 years or older with exsanguinating hemorrhage were enrolled between October 2017 and March 2022 and followed up for 90 days. Intervention: Patients were randomly assigned (1:1 allocation) to a strategy that included REBOA and standard care (n = 46) or standard care alone (n = 44). Main Outcomes and Measures: The primary outcome was all-cause mortality at 90 days. Ten secondary outcomes included mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours; the need for definitive hemorrhage control procedures; time to commencement of definitive hemorrhage control procedures; complications; length of stay; blood product use; and cause of death. Results: Of the 90 patients (median age, 41 years [IQR, 31-59 years]; 62 [69%] were male; and the median Injury Severity Score was 41 [IQR, 29-50]) randomized, 89 were included in the primary outcome analysis because 1 patient in the standard care alone group declined to provide consent for continued participation and data collection 4 days after enrollment. At 90 days, 25 of 46 patients (54%) had experienced all-cause mortality in the REBOA and standard care group vs 18 of 43 patients (42%) in the standard care alone group (odds ratio [OR], 1.58 [95% credible interval, 0.72-3.52]; posterior probability of an OR >1 [indicating increased odds of death with REBOA], 86.9%). Among the 10 secondary outcomes, the ORs for mortality and the posterior probabilities of an OR greater than 1 for 6-month, in-hospital, and 24-, 6-, or 3-hour mortality were all increased in the REBOA and standard care group, and the ORs were increased with earlier mortality end points. There were more deaths due to bleeding in the REBOA and standard care group (8 of 25 patients [32%]) than in standard care alone group (3 of 18 patients [17%]), and most occurred within 24 hours. Conclusions and Relevance: In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone. Trial Registration: isrctn.org Identifier: ISRCTN16184981.

Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products.

Twenty-five years have passed since the first clinical trial utilising mesenchymal stomal/stem cells (MSCs) in 1995. In this time academic research has grown our understanding of MSC biochemistry and our ability to manipulate these cells in vitro using chemical, biomaterial, and mechanical methods. Research has been emboldened by the promise that MSCs can treat illness and repair damaged tissues through their capacity for immunomodulation and differentiation. Since 1995, 31 therapeutic products containing MSCs and/or progenitors have reached the market with the level of in vitro manipulation varying significantly. In this review, we summarise existing therapeutic products containing MSCs or mesenchymal progenitor cells and examine the challenges faced when developing new therapeutic products. Successful progression to clinical trial, and ultimately market, requires a thorough understanding of these hurdles at the earliest stages of in vitro pre-clinical development. It is beneficial to understand the health economic benefit for a new product and the reimbursement potential within various healthcare systems. Pre-clinical studies should be selected to demonstrate efficacy and safety for the specific clinical indication in humans, to avoid duplication of effort and minimise animal usage. Early consideration should also be given to manufacturing: how cell manipulation methods will integrate into highly controlled workflows and how they will be scaled up to produce clinically relevant quantities of cells. Finally, we summarise the main regulatory pathways for these clinical products, which can help shape early therapeutic design and testing.

Alopecia areata: A multifactorial autoimmune condition.

Alopecia areata is an autoimmune disease that results in non-scarring hair loss, and it is clinically characterised by small patches of baldness on the scalp and/or around the body. It can later progress to total loss of scalp hair (Alopecia totalis) and/or total loss of all body hair (Alopecia universalis). The rapid rate of hair loss and disfiguration caused by the condition causes anxiety on patients and increases the risks of developing psychological and psychiatric complications. Hair loss in alopecia areata is caused by lymphocytic infiltrations around the hair follicles and IFN-γ. IgG antibodies against the hair follicle cells are also found in alopecia areata sufferers. In addition, the disease coexists with other autoimmune disorders and can come secondary to infections or inflammation. However, despite the growing knowledge about alopecia areata, the aetiology and pathophysiology of disease are not well defined. In this review we discuss various genetic and environmental factors that cause autoimmunity and describe the immune mechanisms that lead to hair loss in alopecia areata patients.

Mirror Coating Solution for the Cryogenic Einstein Telescope.

Planned cryogenic gravitational-wave detectors will require improved coatings with a strain thermal noise reduced by a factor of 25 compared to Advanced LIGO. We present investigations of HfO_{2} doped with SiO_{2} as a new coating material for future detectors. Our measurements show an extinction coefficient of k=6×10^{-6} and a mechanical loss of ϕ=3.8×10^{-4} at 10 K, which is a factor of 2 below that of SiO_{2}, the currently used low refractive-index coating material. These properties make HfO_{2} doped with SiO_{2} ideally suited as a low-index partner material for use with a-Si in the lower part of a multimaterial coating. Based on these results, we present a multimaterial coating design which, for the first time, can simultaneously meet the strict requirements on optical absorption and thermal noise of the cryogenic Einstein Telescope.

Integrated robotics platform with haptic control differentiates subjects with Parkinson's disease from controls and quantifies the motor effects of levodopa.

BACKGROUND: The use of integrated robotic technology to quantify the spectrum of motor symptoms of Parkinson's Disease (PD) has the potential to facilitate objective assessment that is independent of clinical ratings. The purpose of this study is to use the KINARM exoskeleton robot to (1) differentiate subjects with PD from controls and (2) quantify the motor effects of dopamine replacement therapies (DRTs). METHODS: Twenty-six subjects (Hoehn and Yahr mean 2.2; disease duration 0.5 to 15 years) were evaluated OFF (after > 12 h of their last dose) and ON their DRTs with the Unified Parkinson's Disease Rating Scale (UPDRS) and the KINARM exoskeleton robot. Bilateral upper extremity bradykinesia, rigidity, and postural stability were quantified using a repetitive movement task to hit moving targets, a passive stretch task, and a torque unloading task, respectively. Performance was compared against healthy age-matched controls. RESULTS: Mean hand speed was 41% slower and 25% fewer targets were hit in subjects with PD OFF medication than in controls. Receiver operating characteristic (ROC) area for hand speed was 0.94. The torque required to stop elbow movement during the passive stretch task was 34% lower in PD subjects versus controls and resulted in an ROC area of 0.91. The torque unloading task showed a maximum displacement that was 29% shorter than controls and had an ROC area of 0.71. Laterality indices for speed and end total torque were correlated to the most affected side. Hand speed laterality index had an ROC area of 0.80 against healthy controls. DRT administration resulted in a significant reduction in a cumulative score of parameter Z-scores (a measure of global performance compared to healthy controls) in subjects with clinically effective levodopa doses. The cumulative score was also correlated to UPDRS scores for the effect of DRT. CONCLUSIONS: Robotic assessment is able to objectively quantify parkinsonian symptoms of bradykinesia, rigidity and postural stability similar to the UPDRS. This integrated testing platform has the potential to aid clinicians in the management of PD and help assess the effects of novel therapies.

Control of cell behaviour through nanovibrational stimulation: nanokicking.

Mechanical signals are ubiquitous in our everyday life and the process of converting these mechanical signals into a biological signalling response is known as mechanotransduction. Our understanding of mechanotransduction, and its contribution to vital cellular responses, is a rapidly expanding field of research involving complex processes that are still not clearly understood. The use of mechanical vibration as a stimulus of mechanotransduction, including variation of frequency and amplitude, allows an alternative method to control specific cell behaviour without chemical stimulation (e.g. growth factors). Chemical-independent control of cell behaviour could be highly advantageous for fields including drug discovery and clinical tissue engineering. In this review, a novel technique is described based on nanoscale sinusoidal vibration. Using finite-element analysis in conjunction with laser interferometry, techniques that are used within the field of gravitational wave detection, optimization of apparatus design and calibration of vibration application have been performed. We further discuss the application of nanovibrational stimulation, or 'nanokicking', to eukaryotic and prokaryotic cells including the differentiation of mesenchymal stem cells towards an osteoblast cell lineage. Mechanotransductive mechanisms are discussed including mediation through the Rho-A kinase signalling pathway. Optimization of this technique was first performed in two-dimensional culture using a simple vibration platform with an optimal frequency and amplitude of 1 kHz and 22 nm. A novel bioreactor was developed to scale up cell production, with recent research demonstrating that mesenchymal stem cell differentiation can be efficiently triggered in soft gel constructs. This important step provides first evidence that clinically relevant (three-dimensional) volumes of osteoblasts can be produced for the purpose of bone grafting, without complex scaffolds and/or chemical induction. Initial findings have shown that nanovibrational stimulation can also reduce biofilm formation in a number of clinically relevant bacteria. This demonstrates additional utility of the bioreactor to investigate mechanotransduction in other fields of research.This article is part of a discussion meeting issue 'The promises of gravitational-wave astronomy'.

Predicting the public health benefit of vaccinating cattle against Escherichia coli O157.

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle-human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human-animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases.

Foodborne bacterial pathogens: genome-based approaches for enduring and emerging threats in a complex and changing world.

Foodborne illnesses pose a substantial health and economic burden, presenting challenges in prevention due to the diverse microbial hazards that can enter and spread within food systems. Various factors, including natural, political and commercial drivers, influence food production and distribution. The risks of foodborne illness will continue to evolve in step with these drivers and with changes to food systems. For example, climate impacts on water availability for agriculture, changes in food sustainability targets and evolving customer preferences can all have an impact on the ecology of foodborne pathogens and the agrifood niches that can carry microorganisms. Whole-genome and metagenome sequencing, combined with microbial surveillance schemes and insights from the food system, can provide authorities and businesses with transformative information to address risks and implement new food safety interventions across the food chain. In this Review, we describe how genome-based approaches have advanced our understanding of the evolution and spread of enduring bacterial foodborne hazards as well as their role in identifying emerging foodborne hazards. Furthermore, foodborne hazards exist in complex microbial communities across the entire food chain, and consideration of these co-existing organisms is essential to understanding the entire ecology supporting pathogen persistence and transmission in an evolving food system.

Developing and Investigating a Nanovibration Intervention for the Prevention/Reversal of Bone Loss Following Spinal Cord Injury.

Osteoporosis disrupts the fine-tuned balance between bone formation and resorption, leading to reductions in bone quantity and quality and ultimately increasing fracture risk. Prevention and treatment of osteoporotic fractures is essential for reductions in mortality, morbidity, and the economic burden, particularly considering the aging global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralyzed limbs following complete spinal cord injury (SCI). In vitro nanoscale vibration (1 kHz, 30 or 90 nm amplitude) has been shown to drive differentiation of mesenchymal stem cells toward osteoblast-like phenotypes, enhancing osteogenesis and inhibiting osteoclastogenesis simultaneously. Here, we develop and characterize a wearable device designed to deliver and monitor continuous nanoamplitude vibration to the hindlimb long bones of rats with complete SCI. We investigate whether a clinically feasible dose of nanovibration (two 2 h/day, 5 days/week for 6 weeks) is effective at reversing the established SCI-induced osteoporosis. Laser interferometry and finite element analysis confirmed transmission of nanovibration into the bone, and microcomputed tomography and serum bone formation and resorption markers assessed effectiveness. The intervention did not reverse SCI-induced osteoporosis. However, serum analysis indicated an elevated concentration of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) in rats receiving 40 nm amplitude nanovibration, suggesting increased synthesis of type 1 collagen, the major organic component of bone. Therefore, enhanced doses of nanovibrational stimulus may yet prove beneficial in attenuating/reversing osteoporosis, particularly in less severe forms of osteoporosis.

Cervical spine immobilisation following blunt trauma in pre-hospital and emergency care: A systematic review.

OBJECTIVES: To assess whether different cervical spine immobilisation strategies (full immobilisation, movement minimisation or no immobilisation), impact neurological and/or other outcomes for patients with suspected cervical spinal injury in the pre-hospital and emergency department setting. DESIGN: Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Library and two research registers were searched until September 2023. ELIGIBILITY CRITERIA: All comparative studies (prospective or retrospective) that examined the potential benefits and/or harms of immobilisation practices during pre-hospital and emergency care of patients with a potential cervical spine injury (pre-imaging) following blunt trauma. DATA EXTRACTION AND SYNTHESIS: Two authors independently selected and extracted data. Risk of bias was appraised using the Cochrane ROBINS-I tool for non-randomised studies. Data were synthesised without meta-analysis. RESULTS: Six observational studies met the inclusion criteria. The methodological quality was variable, with most studies having serious or critical risk of bias. The effect of cervical spine immobilisation practices such as full immobilisation or movement minimisation during pre-hospital and emergency care did not show clear evidence of benefit for the prevention of neurological deterioration, spinal injuries and death compared with no immobilisation. However, increased pain, discomfort and anatomical complications were associated with collar application during immobilisation. CONCLUSIONS: Despite the limited evidence, weak designs and limited generalisability, the available data suggest that pre-hospital cervical spine immobilisation (full immobilisation or movement minimisation) was of uncertain value due to the lack of demonstrable benefit and may lead to potential complications and adverse outcomes. High-quality randomised comparative studies are required to address this important question. TRIAL REGISTRATION: PROSPERO REGISTRATION Fiona Lecky, Abdullah Pandor, Munira Essat, Anthea Sutton, Carl Marincowitz, Gordon Fuller, Stuart Reid, Jason Smith. A systematic review of cervical spine immobilisation following blunt trauma in pre-hospital and emergency care. PROSPERO 2022 CRD42022349600 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022349600.

Surface-Modified Piezoelectric Copolymer Poly(vinylidene fluoride-trifluoroethylene) Supporting Physiological Extracellular Matrixes to Enhance Mesenchymal Stem Cell Adhesion for Nanoscale Mechanical Stimulation.

There is an unmet clinical need to provide viable bone grafts for clinical use. Autologous bone, one of the most commonly transplanted tissues, is often used but is associated with donor site morbidity. Tissue engineering strategies to differentiate an autologous cell source, such as mesenchymal stromal cells (MSCs), into a potential bone-graft material could help to fulfill clinical demand. However, osteogenesis of MSCs can typically require long culture periods that are impractical in a clinical setting and can lead to significant cost. Investigation into strategies that optimize cell production is essential. Here, we use the piezoelectric copolymer poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE), functionalized with a poly(ethyl acrylate) (PEA) coating that drives fibronectin network formation, to enhance MSC adhesion and to present growth factors in the solid phase. Dynamic electrical cues are then incorporated, via a nanovibrational bioreactor, and the MSC response to electromechanical stimulation is investigated.

An ecological approach to assessing the epidemiology of antimicrobial resistance in animal and human populations.

We examined long-term surveillance data on antimicrobial resistance (AMR) in Salmonella Typhimurium DT104 (DT104) isolates from concurrently sampled and sympatric human and animal populations in Scotland. Using novel ecological and epidemiological approaches to examine diversity, and phenotypic and temporal relatedness of the resistance profiles, we assessed the more probable source of resistance of these two populations. The ecological diversity of AMR phenotypes was significantly greater in human isolates than in animal isolates, at the resolution of both sample and population. Of 5200 isolates, there were 65 resistance phenotypes, 13 unique to animals, 30 unique to humans and 22 were common to both. Of these 22, 11 were identified first in the human isolates, whereas only five were identified first in the animal isolates. We conclude that, while ecologically connected, animals and humans have distinguishable DT104 communities, differing in prevalence, linkage and diversity. Furthermore, we infer that the sympatric animal population is unlikely to be the major source of resistance diversity for humans. This suggests that current policy emphasis on restricting antimicrobial use in domestic animals may be overly simplistic. While these conclusions pertain to DT104 in Scotland, this approach could be applied to AMR in other bacteria-host ecosystems.

Using sequence data to identify alternative routes and risk of infection: a case-study of campylobacter in Scotland.

BACKGROUND: Genetic typing data are a potentially powerful resource for determining how infection is acquired. In this paper MLST typing was used to distinguish the routes and risks of infection of humans with Campylobacter jejuni from poultry and ruminant sources METHODS: C. jejuni samples from animal and environmental sources and from reported human cases confirmed between June 2005 and September 2006 were typed using MLST. The STRUCTURE software was used to assign the specific sequence types of the sporadic human cases to a particular source. We then used mixed case-case logistic regression analysis to compare the risk factors for being infected with C. jejuni from different sources. RESULTS: A total of 1,599 (46.3%) cases were assigned to poultry, 1,070 (31.0%) to ruminant and 67 (1.9%) to wild bird sources; the remaining 715 (20.7%) did not have a source that could be assigned with a probability of greater than 0.95. Compared to ruminant sources, cases attributed to poultry sources were typically among adults (odds ratio (OR) = 1.497, 95% confidence intervals (CIs) = 1.211, 1.852), not among males (OR = 0.834, 95% CIs = 0.712, 0.977), in areas with population density of greater than 500 people/km2 (OR = 1.213, 95% CIs = 1.030, 1.431), reported in the winter (OR = 1.272, 95% CIs = 1.067, 1.517) and had undertaken recent overseas travel (OR = 1.618, 95% CIs = 1.056, 2.481). The poultry assigned strains had a similar epidemiology to the unassigned strains, with the exception of a significantly higher likelihood of reporting overseas travel in unassigned strains. CONCLUSIONS: Rather than estimate relative risks for acquiring infection, our analyses show that individuals acquire C. jejuni infection from different sources have different associated risk factors. By enhancing our ability to identify at-risk groups and the times at which these groups are likely to be at risk, this work allows public health messages to be targeted more effectively. The rapidly increasing capacity to conduct genetic typing of pathogens makes such traced epidemiological analysis more accessible and has the potential to substantially enhance epidemiological risk factor studies.

Gasterophilosis: a major cause of rectal prolapse in working donkeys in Ethiopia.

A retrospective study was conducted to investigate the cause of rectal prolapse in working donkeys in Ethiopia. Analysis of data on rectal prolapse cases obtained from the Donkey Health and Welfare Project clinic at the School of Veterinary Medicine, Addis Ababa University, from 1995 to 2004 revealed that 83.6% (n = 177) of the cases were associated with Gasterophilus nasalis. The rest 10.7% and 5.7% were associated with work-related (overloading) cause and diarrhoea, respectively. The mean and median numbers of G. nasalis recovered from the rectum of infected donkeys were 66 and 64, respectively, with a range of 2-195. Over 100 G. nasalis larvae were recovered from the rectum of 22% of the donkeys. Circular demarcated ulcer-like and deep circumferential pits or ring-like mucosal lesions were found at the larval attachment sites. G. nasalis infection and the associated rectal prolapse were observed year round. However, the intensity of rectal larval infection and incidence of rectal prolapse were significantly higher during the rainy season (P < 0.01). Age and sex of the donkeys had no significant effect on the intensity of rectal larval infection and incidence of rectal prolapse (P > 0.05).

Spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury in skeletally mature rats.

Objective: Characterise the spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury (SCI) in the skeletally mature rat in the acute (4-week) period following injury. Methods: The spinal cord of 5-month old male rats was transected at the T9 level. Outcome measures were assessed using micro-computed tomography, three-point bending and serum markers at 1-, 2-, and 4-weeks post-transection. Comparison was made with time-0 and sham animals. Results: Lower levels of circulating serum bone formation markers and higher bone resorption markers suggested uncoupled bone turnover as early at 1-week post-transection. Micro-computed tomography showed metaphyseal and epiphyseal trabecular bone loss was observed only at 4-weeks post-transection. The bone loss was site-specific with a more severe reduction in trabecular BV/TV observed in the metaphyseal (50%) relative to epiphyseal (19%) region. Metaphyseal trabecular bone exhibited a 54% reduction in connectivity density while the epiphyseal trabecular bone was unaffected. Cortical bone deficits were not seen over the time periods examined. Conclusions: The study demonstrates that the skeletally mature spinal cord transected rat model replicates the biphasic pattern of osteoporotic changes observed in the human SCI population, providing a relevant model for testing the efficacy of interventions against SCI-induced osteoporosis.

Contrasting long-term dynamics of antimicrobial resistance and virulence plasmids in Salmonella Typhimurium from animals.

Plasmids are mobile elements that can carry genes encoding traits of clinical concern, including antimicrobial resistance (AMR) and virulence. Population-level studies of Enterobacterales, including Escherichia coli, Shigella and Klebsiella, indicate that plasmids are important drivers of lineage expansions and dissemination of AMR genes. Salmonella Typhimurium is the second most common cause of salmonellosis in humans and livestock in the UK and Europe. The long-term dynamics of plasmids between S. Typhimurium were investigated using isolates collected through national surveillance of animals in England and Wales over a 25-year period. The population structure of S. Typhimurium and its virulence plasmid (where present) were inferred through phylogenetic analyses using whole-genome sequence data for 496 isolates. Antimicrobial resistance genes and plasmid markers were detected in silico. Phenotypic plasmid characterization, using the Kado and Liu method, was used to confirm the number and size of plasmids. The differences in AMR and plasmids between clades were striking, with livestock clades more likely to carry one or more AMR plasmid and be multi-drug-resistant compared to clades associated with wildlife and companion animals. Multiple small non-AMR plasmids were distributed across clades. However, all hybrid AMR-virulence plasmids and most AMR plasmids were highly clade-associated and persisted over decades, with minimal evidence of horizontal transfer between clades. This contrasts with the role of plasmids in the short-term dissemination of AMR between diverse strains in other Enterobacterales in high-antimicrobial-use settings, with implications for predicting plasmid dissemination amongst S. Typhimurium.

Generating social network data using partially described networks: an example informing avian influenza control in the British poultry industry.

BACKGROUND: Targeted sampling can capture the characteristics of more vulnerable sectors of a population, but may bias the picture of population level disease risk. When sampling network data, an incomplete description of the population may arise leading to biased estimates of between-host connectivity. Avian influenza (AI) control planning in Great Britain (GB) provides one example where network data for the poultry industry (the Poultry Network Database or PND), targeted large premises and is consequently demographically biased. Exposing the effect of such biases on the geographical distribution of network properties could help target future poultry network data collection exercises. These data will be important for informing the control of potential future disease outbreaks. RESULTS: The PND was used to compute between-farm association frequencies, assuming that farms sharing the same slaughterhouse or catching company, or through integration, are potentially epidemiologically linked. The fitted statistical models were extrapolated to the Great Britain Poultry Register (GBPR); this dataset is more representative of the poultry industry but lacks network information. This comparison showed how systematic biases in the demographic characterisation of a network, resulting from targeted sampling procedures, can bias the derived picture of between-host connectivity within the network. CONCLUSIONS: With particular reference to the predictive modeling of AI in GB, we find significantly different connectivity patterns across GB when network estimates incorporate the more demographically representative information provided by the GBPR; this has not been accounted for by previous epidemiological analyses. We recommend ranking geographical regions, based on relative confidence in extrapolated estimates, for prioritising further data collection. Evaluating whether and how the between-farm association frequencies impact on the risk of between-farm transmission will be the focus of future work.

Gravitational Wave Detection by Interferometry (Ground and Space).

Significant progress has been made in recent years on the development of gravitational-wave detectors. Sources such as coalescing compact binary systems, neutron stars in low-mass X-ray binaries, stellar collapses and pulsars are all possible candidates for detection. The most promising design of gravitational-wave detector uses test masses a long distance apart and freely suspended as pendulums on Earth or in drag-free spacecraft. The main theme of this review is a discussion of the mechanical and optical principles used in the various long baseline systems in operation around the world - LIGO (USA), Virgo (Italy/France), TAMA300 and LCGT (Japan), and GEO600 (Germany/U.K.) - and in LISA, a proposed space-borne interferometer. A review of recent science runs from the current generation of ground-based detectors will be discussed, in addition to highlighting the astrophysical results gained thus far. Looking to the future, the major upgrades to LIGO (Advanced LIGO), Virgo (Advanced Virgo), LCGT and GEO600 (GEO-HF) will be completed over the coming years, which will create a network of detectors with the significantly improved sensitivity required to detect gravitational waves. Beyond this, the concept and design of possible future "third generation" gravitational-wave detectors, such as the Einstein Telescope (ET), will be discussed.