Low fitness, low body mass and prior injury predict injury risk during military recruit training: a prospective cohort study in the British Army

Background Injuries sustained by military recruits during initial training impede training progression and military readiness while increasing financial costs. This study investigated training-related injuries and injury risk factors among British Army infantry recruits. Methods Recruits starting infantry training at the British Army Infantry Training Centre between September 2008 and March 2010 were eligible to take part. Information regarding lifestyle behaviours and injury history was collected using the Military Pre-training Questionnaire. Sociodemographic, anthropometric, physical fitness and injury (lower limb and lower back) data were obtained from Army databases. Univariable and multivariable Cox regression models were used to explore the association between time to first training injury and potential risk factors. Results 58% (95% CI 55% to 60%) of 1810 recruits sustained at least 1 injury during training. Overuse injuries were more common than traumatic injuries (65% and 35%, respectively). The lower leg accounted for 81% of all injuries, and non-specific soft tissue damage was the leading diagnosis (55% of all injuries). Injuries resulted in 122 (118 to 126) training days lost per 1000 person-days. Slower 2.4 km run time, low body mass, past injury and shin pain were independently associated with higher risk of any injury. Conclusions There was a high incidence of overuse injuries in British Army recruits undertaking infantry training. Recruits with lower pretraining fitness levels, low body mass and past injuries were at higher risk. Faster 2.4 km run time performance and minimal body mass standards should be considered for physical entry criteria

Neuronal pentraxins mediate synaptic refinement in the developing visual system

Peer reviewedPublisher PD

PPAR-γ in Macrophages Limits Pulmonary Inflammation and Promotes Host Recovery Following Respiratory Viral Infection

Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections.IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections

Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile

Persistent near real-time passive acoustic monitoring for baleen whales from a moored buoy: System description and evaluation

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Baumgartner, M. F., Bonnell, J., Van Parijs, S. M., Corkeron, P. J., Hotchkin, C., Ball, K., Pelletier, L., Partan, J., Peters, D., Kemp, J., Pietro, J., Newhall, K., Stokes, A., Cole, T. V. N., Quintana, E., & Kraus, S. D. Persistent near real-time passive acoustic monitoring for baleen whales from a moored buoy: System description and evaluation. Methods in Ecology and Evolution, 10(9), (2019): 1476-1489, doi: 10.1111/2041-210X.13244.1. Managing interactions between human activities and marine mammals often relies on an understanding of the real‐time distribution or occurrence of animals. Visual surveys typically cannot provide persistent monitoring because of expense and weather limitations, and while passive acoustic recorders can monitor continuously, the data they collect are often not accessible until the recorder is recovered. 2. We have developed a moored passive acoustic monitoring system that provides near real‐time occurrence estimates for humpback, sei, fin and North Atlantic right whales from a single site for a year, and makes those occurrence estimates available via a publicly accessible website, email and text messages, a smartphone/tablet app and the U.S. Coast Guard's maritime domain awareness software. We evaluated this system using a buoy deployed off the coast of Massachusetts during 2015–2016 and redeployed again during 2016–2017. Near real‐time estimates of whale occurrence were compared to simultaneously collected archived audio as well as whale sightings collected near the buoy by aerial surveys. 3. False detection rates for right, humpback and sei whales were 0% and nearly 0% for fin whales, whereas missed detection rates at daily time scales were modest (12%–42%). Missed detections were significantly associated with low calling rates for all species. We observed strong associations between right whale visual sightings and near real‐time acoustic detections over a monitoring range 30–40 km and temporal scales of 24–48 hr, suggesting that silent animals were not especially problematic for estimating occurrence of right whales in the study area. There was no association between acoustic detections and visual sightings of humpback whales. 4. The moored buoy has been used to reduce the risk of ship strikes for right whales in a U.S. Coast Guard gunnery range, and can be applied to other mitigation applications.We thank Annamaria Izzi, Danielle Cholewiak and Genevieve Davis of the NOAA NEFSC for assistance in developing the analyst protocol. We are grateful to the NOAA NEFSC aerial survey observers (Leah Crowe, Pete Duley, Jen Gatzke, Allison Henry, Christin Khan and Karen Vale) and the NEAq aerial survey observers (Angela Bostwick, Marianna Hagbloom and Paul Nagelkirk). Danielle Cholewiak and three anonymous reviewers provided constructive criticism on earlier drafts of the manuscript. Funding for this project was provided by the NOAA NEFSC, NOAA Advanced Sampling Technology Work Group, Environmental Security Technology Certification Program of the U.S. Department of Defense, the U.S. Navy's Living Marine Resources Program, Massachusetts Clean Energy Center and the Bureau of Ocean Energy Management. Funding from NOAA was facilitated by the Cooperative Institute for the North Atlantic Region (CINAR) under Cooperative Agreement NA14OAR4320158

Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates

Opportunities for improving animal welfare in rodent models of epilepsy and seizures

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)

Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin

Oral abstracts 1: SpondyloarthropathiesO1. Detecting axial spondyloarthritis amongst primary care back pain referrals

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn's disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interes