The Effects of Fire Fighting and On-Scene Rehabilitation on Hemostatis

Fire fighting is a dangerous occupation – in part because firefighters are called upon to perform strenuous physical activity in hot, hostile environments. Each year, approximately 100 firefighters lose their lives in the line of duty and tens of thousands are injured. Over the past 15 years, approximately 45% of line of duty deaths have been attributed to heart attacks and another 650-1,000 firefighters suffer non-fatal heart attacks in the line of duty each year. From 1990 to 2004, the total number of fireground injuries has declined, yet during this same period, the number of cases related to the leading cause of injury - overexertion/strain – remained relatively constant. It is well recognized that fire fighting leads to increased cardiovascular and thermal strain. However, the time course of recovery from fire fighting is not well documented, despite the fact that a large percentage of fire fighting fatalities occur after fire fighting activity. Furthermore, on scene rehabilitation (OSR) has been broadly recommended to mitigate the cardiovascular and thermal strain associated with performing strenuous fire fighting activity, yet the efficacy of different rehabilitation interventions has not been documented. Twenty-five firefighters were recruited to participate in a “within-subjects, repeated measures” study designed to describe the acute effects of fire fighting on a broad array of physiological and psychological measures and several key cardiovascular variables. This study provided the first detailed documentation of the time course of recovery during 2½ hours post-fire fighting. Additionally, we compared two OSR strategies (standard and enhanced) to determine their effectiveness.published or submitted for publicationnot peer reviewe

Investigation of the functional roles of host cell proteins involved in Coronavirus infection using highly specific and scalable RNA interference (RNAi) approach

Since its identification in the 1990s, the RNA interference (RNAi) pathway has proven extremely useful in elucidating the function of proteins in the context of cells and even whole organisms. In particular, this sequence-specific and powerful loss-of-function approach has greatly simplified the study of the role of host cell factors implicated in the life cycle of viruses. Here, we detail the RNAi method we have developed and used to specifically knock down the expression of ezrin, an actin binding protein that was identified by yeast two-hybrid screening to interact with the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) spike (S) protein. This method was used to study the role of ezrin, specifically during the entry stage of SARS-CoV infection

Distributed probing of chromatin structure in vivo reveals pervasive chromatin accessibility for expressed and non-expressed genes during tissue differentiation in C. elegans

<p>Abstract</p> <p>Background</p> <p>Tissue differentiation is accompanied by genome-wide changes in the underlying chromatin structure and dynamics, or epigenome. By controlling when, where, and what regulatory factors have access to the underlying genomic DNA, the epigenome influences the cell's transcriptome and ultimately its function. Existing genomic methods for analyzing cell-type-specific changes in chromatin generally involve two elements: (i) a source for purified cells (or nuclei) of distinct types, and (ii) a specific treatment that partitions or degrades chromatin by activity or structural features. For many cell types of great interest, such assays are limited by our inability to isolate the relevant cell populations in an organism or complex tissue containing an intertwined mixture of other cells. This limitation has confined available knowledge of chromatin dynamics to a narrow range of biological systems (cell types that can be sorted/separated/dissected in large numbers and tissue culture models) or to amalgamations of diverse cell types (tissue chunks, whole organisms).</p> <p>Results</p> <p>Transgene-driven expression of DNA/chromatin modifying enzymes provides one opportunity to query chromatin structures in expression-defined cell subsets. In this work we combine <it>in vivo </it>expression of a bacterial DNA adenine methyltransferase (DAM) with high throughput sequencing to sample tissue-specific chromatin accessibility on a genome-wide scale. We have applied the method (DALEC: Direct Asymmetric Ligation End Capture) towards mapping a cell-type-specific view of genome accessibility as a function of differentiated state. Taking advantage of <it>C. elegans </it>strains expressing the DAM enzyme in diverse tissues (body wall muscle, gut, and hypodermis), our efforts yield a genome-wide dataset measuring chromatin accessibility at each of 538,000 DAM target sites in the <it>C. elegans </it>(diploid) genome.</p> <p>Conclusions</p> <p>Validating the DALEC mapping results, we observe a strong association between observed coverage by nucleosomes and low DAM accessibility. Strikingly, we observed no extended regions of inaccessible chromatin for any of the tissues examined. These results are consistent with "local choreography" models in which differential gene expression is driven by intricate local rearrangements of chromatin structure rather than gross impenetrability of large chromosomal regions.</p

Can Fire and Rescue Services and the National Health Service work together to improve the safety and wellbeing of vulnerable older people? Design of a proof of concept study

Older adults are at increased risk both of falling and of experiencing accidental domestic fire. In addition to advanced age, these adverse events share the risk factors of balance or mobility problems, cognitive impairment and socioeconomic deprivation. For both events, the consequences include significant injury and death, and considerable socioeconomic costs for the individual and informal carers, as well as for emergency services, health and social care agencies.Secondary prevention services for older people who have fallen or who are identifiable as being at high risk of falling include NHS Falls clinics, where a multidisciplinary team offers an individualised multifactorial targeted intervention including strength and balance exercise programmes, medication changes and home hazard modification. A similar preventative approach is employed by most Fire and Rescue Services who conduct Home Fire Safety Visits to assess and, if necessary, remedy domestic fire risk, fit free smoke alarms with instruction for use and maintenance, and plan an escape route. We propose that the similarity of population at risk, location, specific risk factors and the commonality of preventative approaches employed could offer net gains in terms of feasibility, effectiveness and acceptability if activities within these two preventative approaches were to be combined

The Risk of Unexploded Ordnance on Construction Sites in London

Greater London, among many large cities, was subject to bombing by the German military in both the World Wars and was the target of many air raids during the Second World War (WW2). This was particularly the case during the Blitz, September 1940 – May 1941, when over 28,000 high explosive bombs and parachute mines were dropped on London. Post war research conducted in 1949 estimated that approximately 12,750 t of bombs, including V1 and V2 rockets, were dropped on London. The night of 16th – 17th April 1941 was one of the worst bombing raids, when 446 t of bombs were dropped on London and over 58 t did not detonate. Unexploded bombs remain buried underground today, as they were unidentified at the time or abandoned owing to difficulties in recovering them. Uncharted bombs continue to pose a potentially significant hazard for developments around London. This paper considers the probability of discovering unexploded ordnance (UXO), particularly WW2 ordnance, during intrusive groundworks in London. The prevalence of unexploded ordnance has been assessed using data obtained from governmental organisations to estimate the likelihood of discovery in London

Inducible systemic RNA silencing in Caenorhabditis elegans

Introduction of double-stranded RNA (dsRNA) can elicit a gene-specific RNA interference response in a variety of organisms and cell types. In many cases, this response has a systemic character in that silencing of gene expression is observed in cells distal from the site of dsRNA delivery. The molecular mechanisms underlying the mobile nature of RNA silencing are unknown. For example, although cellular entry of dsRNA is possible, cellular exit of dsRNA from normal animal cells has not been directly observed. We provide evidence that transgenic strains of Caenorhabditis elegans transcribing dsRNA from a tissue-specific promoter do not exhibit comprehensive systemic RNA interference phenotypes. In these same animals, modifications of environmental conditions can result in more robust systemic RNA silencing. Additionally, we find that genetic mutations can influence the systemic character of RNA silencing in C. elegans and can separate mechanisms underlying systemic RNA silencing into tissue-specific components. These data suggest that trafficking of RNA silencing signals in C. elegans is regulated by specific physiological and genetic factors

Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant

Predicting invasive fungal disease due to Candida species in non-neutropenic, critically ill, adult patients in United Kingdom critical care units.

BACKGROUND: Given the predominance of invasive fungal disease (IFD) amongst the non-immunocompromised adult critically ill population, the potential benefit of antifungal prophylaxis and the lack of generalisable tools to identify high risk patients, the aim of the current study was to describe the epidemiology of IFD in UK critical care units, and to develop and validate a clinical risk prediction tool to identify non-neutropenic, critically ill adult patients at high risk of IFD who would benefit from antifungal prophylaxis. METHODS: Data on risk factors for, and outcomes from, IFD were collected for consecutive admissions to adult, general critical care units in the UK participating in the Fungal Infection Risk Evaluation (FIRE) Study. Three risk prediction models were developed to model the risk of subsequent Candida IFD based on information available at three time points: admission to the critical care unit, at the end of 24 h and at the end of calendar day 3 of the critical care unit stay. The final model at each time point was evaluated in the three external validation samples. RESULTS: Between July 2009 and April 2011, 60,778 admissions from 96 critical care units were recruited. In total, 359 admissions (0.6 %) were admitted with, or developed, Candida IFD (66 % Candida albicans). At the rate of candidaemia of 3.3 per 1000 admissions, blood was the most common Candida IFD infection site. Of the initial 46 potential variables, the final admission model and the 24-h model both contained seven variables while the end of calendar day 3 model contained five variables. The end of calendar day 3 model performed the best with a c index of 0.709 in the full validation sample. CONCLUSIONS: Incidence of Candida IFD in UK critical care units in this study was consistent with reports from other European epidemiological studies, but lower than that suggested by previous hospital-wide surveillance in the UK during the 1990s. Risk modeling using classical statistical methods produced relatively simple risk models, and associated clinical decision rules, that provided acceptable discrimination for identifying patients at 'high risk' of Candida IFD. TRIAL REGISTRATION: The FIRE Study was reviewed and approved by the Bolton NHS Research Ethics Committee (reference: 08/H1009/85), the Scotland A Research Ethics Committee (reference: 09/MRE00/76) and the National Information Governance Board (approval number: PIAG 2-10(f)/2005)