Evaluation of a portable, lightweight modular system to deliver high inspired oxygen to trauma casualties without the use of pressurised cylinders.

INTRODUCTION: Administering supplemental oxygen is a standard of care for trauma casualties to minimise the deleterious effects of hypoxaemia. Forward deployment of oxygen using pressurised cylinders is challenging, for example, logistics (weight and finite resource) and environmental risk (fire and explosion). Oxygen concentrators may overcome these challenges. Although previous studies successfully demonstrated fractional inspired oxygen (FiO2) >0.8 using oxygen concentrators and ventilators, the systems did not fulfil the size, weight and power requirements of agile military medical units. This study evaluated whether a modular system of commercially available clinical devices could supply high FiO2 to either ventilated or spontaneously breathing casualties. METHODS: As a proof of principle, we configured an Inogen One G5 oxygen concentrator, Ventway Sparrow ventilator and Wenoll rebreather system to ventilate a simulated lung (tidal volume 500 mL). Casualty oxygen consumption (gas withdrawal inspiratory limb) and carbon dioxide (CO2) production (CO2 added expiratory limb) were simulated (respiratory quotient of 0.7-0.8). Three circuit configurations were evaluated: open (supplementary oxygen introduced into air inlet of ventilator); semiclosed (ventilator replaces rebreather bag of Wenoll, oxygen connected to either ventilator or Wenoll); and semiclosed with reservoir tubing (addition of 'deadspace' tube between ventilator patient circuit and Wenoll). Data presented as mean and 95% reference range. RESULTS: There were modest increases in FiO2 with increasing Inogen settings in 'open' configuration 0.23 (0.23-0.24) and 0.30 (0.28-0.32) (Inogen output 420 and 1260 mL/min, respectively). With the 'semiclosed' configuration and oxygen added directly into rebreather circuit, FiO2 increased to 0.36 (0.36-0.37). The addition of the 'reservoir tubing' elevated FiO2 to 0.78 (0.71-0.85). FiO2 remained stable over a 4-hour evaluation period. Fractional inspired carbon dioxide CO2 increased over time, reaching 0.005 after 170 (157-182) min. CONCLUSION: Combining existing lightweight devices can deliver high (>0.8) FiO2 and offers a potential solution for the forward deployment of oxygen without needing pressurised cylinders.

LMIC Research Centers' Experiences Hosting U.S. and LMIC Trainees: Evaluation of the Fogarty Global Health Fellows and Scholars Program, 2012 to 2020.

In this mixed-methods study, we explore themes that emerged from a survey assessing the programmatic experiences of mentors and administrators at institutions in low- and middle-income countries (LMICs) hosting trainees supported by the Fogarty International Center's Global Health Program for Fellows and Scholars. A total of 89 of 170 potential respondents representing 31 countries completed the survey (response rate, 52.4%). There was agreement among respondents that their institutions received sufficient funds to support trainees and had the capacity to manage operational and financial aspects of the program. A majority also agreed that both LMIC and U.S. trainees were beneficial to the host institutions, and that trainee projects were relevant to the needs of the host country. Respondents felt that program benefits to LMIC trainees could be improved by increasing the research consumables budget, increasing the flexibility of program timelines, and increasing engagement between LMIC and U.S. trainees and institutions. Respondents indicated that both U.S. and LMIC trainees behaved professionally (including demonstrating respectful and ethical behavior) and took appropriate initiative to conduct their research projects. Findings from this study will help inform innovations to similar training initiatives that will enhance sustainability and improve program performance, and will be responsive to local needs.

Building Physician-Scientist Skills in R Programming:A Short Workshop Report.

Introduction: Statistical analysis programs require coding experience and a basic understanding of programming, skills which are not taught as part of medical school or residency curricula. Methods: We conducted a five-day course for early-career Nigerian physician-scientists interested in learning common statistical tests and acquiring R programming skills. The workshop included didactic presentations, small group learning activities, and interactive discussions. A baseline questionnaire captured participant demographics and solicited participants' level of confidence in understanding/performing common statistical tests. REDCap questionnaires were emailed to obtain feedback on educational format and content. A post-workshop assessment covered participants' overall impression of the program. Results: A total of 23 participants attended the program. Most participants were male (n=14, 60.9%) and at an early stage in their career (assistant professor, n=20, 87.0%). Approximately 70% of respondents indicated having received some prior training in statistics. The proportion of participants without experience using R and SAS software (90% and 85%, respectively) was greater than the corresponding proportions for Stata (55%) and SPSS (20%). Prior to the workshop, most respondents expressed being "not at all confident" in performing one-way ANOVA (60%), logistic regression (68%), simple linear regression (60%), and McNemar's test (80%). There was a statistically significant post-workshop improvement in the level of confidence in understanding and performing common statistical tests. The course was rated on a 0-100 scale as "moderately difficult" (mean ± SD: 51.7 ± 19.5). Most participants felt comfortable in putting the knowledge learned into practice (82.2 ± 17.1). Conclusion and Public Health Implications: Introductory R can be taught to junior physician-scientists in resource-limited settings and can inform the development and implementation of similar training initiatives in analogous settings.

A canine distemper virus seroprevalence study of dogs on three islands in the Torres Strait region, Australia.

Canine distemper virus (CDV) can cause mortality in domestic dogs, which is easily prevented by the consistent application of vaccination protocols. The aim of this study was to determine if the dog populations of three strategically located islands in the Torres Strait of Australia, adjacent to Papua New Guinea, are infected by CDV. Eighty-four serum samples were collected from 70 dogs resident on Saibai, Dauan and Boigu Islands during 2017-2018. Sera were tested for CDV antibodies by a virus neutralization test (VNT). Overall, 7 (8.3%) sera from 6 (8.6%) dogs resident on all three islands were test positive. VNT titres ranged from 20 to >1280. Male adult dogs were more commonly seropositive than female and juvenile dogs. Considering the origin and age of test positive dogs, and veterinary visits to these islands, it was concluded that there is evidence of exposure to a field strain of CDV - rather than previous vaccination - in 4 of the 70 dogs (5.7%) tested in this study. Given the strategic location of these islands in a zone of high biosecurity risk, ongoing surveillance of pathogens such as CDV could inform on potential disease spread pathways in this region. In addition, the presence of high serological titres in the apparent absence of clinical disease requires further investigation.

Neutron activation analysis for the characterization of seawater uranium adsorbents.

This work details the development of an iterative neutron activation analysis (NAA) based workflow to precisely quantify metal ion uptake in an adsorbent. The workflow is iterative because it explores the dependence between independent variables defining the adsorbent fabrication procedure and the time-dependent uptake. It can be adapted to other adsorbents provided they have an affinity for ions which are amenable to efficient quantification using NAA. For this work, the ability of silver nanoparticles to mitigate the negative effects of biofouling on uranium transfer to an adsorbent was ultimately of interest, and hence motivates the development of this method. The limits of U detection and quantification were found to be 0.609 and 3.01µgg-1, respectively; these were obtained using modest irradiation and counting times. The uncertainties arising from the NAA procedure were no more than 9.9%, far smaller than other sources of uncertainty present in the analysis. These results provided solid evidence that adsorbent shape and structure, rather than uniformity of composition, drives variability in adsorption of uranium.

Clinical care in the "Hot Zone".

The threat of chemical, biological, radiological and nuclear incidents is unlikely to decrease and preparations to deal with this type of incident are well established in most European emergency medical systems. In the UK medical care is not currently provided in the "Hot" or contaminated zone. This article discusses the background to the current threat and suggests that, where survivors are present in the "Hot Zone", medical care should be started there to minimise delay and maximise the chances of survival.

Differential regulation of immune responses by odontoblasts.

Odontoblasts (OBs) are cells lining the inner surface of the tooth. Their potential role in host defenses within the tooth is suggested by their production of antimicrobial beta-defensins, but their role needs confirmation. The present study sought to define the roles of human OBs in microbial recognition and innate host responses. Toll-like receptor 2 (TLR2) and TLR4, as well as CCR6, were immunolocalized in human OBs and their dentinal processes in situ. To examine OB function we used organotypic tooth crown cultures to maintain human OBs within their dentin scaffold. Cells in the OB layer of cultured and non-cultured crown preparations expressed mRNA for several markers of innate immunity including chemokine CCL20, chemokine receptor CCR6, TLR2, TLR4 and the OB marker dentin sialophosphoprotein (DSPP). Expression of human beta-defensin 1 (hBD1), hBD2, hBD3, interleukin-8 (IL-8), and CCL20 increased with time in culture. Tooth crown odontoblast (TcOB) cultures were stimulated with agonist that was specific for TLR2 (Pam3CSK4) or TLR4 [Escherichia coli lipopolysaccharide (LPS)]. Nuclear factor-kappaB assays confirmed the TLR2 activity of Pam3CSK4 and the TLR4 activity of LPS. LPS up-regulated IL-1beta, tumor necrosis factor-alpha (TNF-alpha), CCL20, hBD2, IL-8, TLR2 and TLR4; however, Pam3CSK4 down-regulated these mRNAs. IL-1beta, TNF-alpha, CCL20 were also up-regulated from six-fold to 30-fold in TcOB preparations from decayed teeth. Our results show for the first time that OBs express microbial pattern recognition receptors in situ, thus allowing differential responses to gram-positive and gram-negative bacteria, and suggest that pro-inflammatory cytokines and innate immune responses in decayed teeth may result from TLR4 signaling.

Respiratory protection for Health Care Workers.

Chemical, Biological, Radiological and Nuclear incidents are rare, but the likelihood of any medical facility having to deal with contaminated or contagious casualties is not, Health Care Workers (HCW) often being exposed to infectious or toxic substances. Although medical staff routinely take measures to protect themselves against exposure to infection by wearing protective clothing, they rarely consider the inhalational route as a threat. This paper presents a series of cases where HCW's have been exposed to toxic or infectious material through the respiratory route, discusses standards of respiratory protection and describes how this risk can be mitigated to protect medical personnel.

Accidental hypothermia.

Hypothermia is a multi-system disorder that significantly increases morbidity and mortality in the injured patient. It is an environmental hazard that can kill in its own right. The most difficult differentiation and management decisions are likely to be with victims in Stage II or Stage III hypothermia. Following successful rescue in these cases, arresting any further cooling of the core temperature, instituting rewarming strategies and careful patient handling will be the key factors in reducing morbidity and mortality.

Altered localization of Cav1.2 (L-type) calcium channels in nerve fibers, Schwann cells, odontoblasts, and fibroblasts of tooth pulp after tooth injury.

We have determined the localization of Cav1.2 (L-Type) Ca2+ channels in the cells and nerve fibers in molars of normal or injured rats. We observed high levels of immunostaining of L-type Ca2+ channels in odontoblast cell bodies and their processes, in fibroblast cell bodies and in Schwann cells. Many Cav1.2-containing unmyelinated and myelinated axons were also present in root nerves and proximal branches in coronal pulp, but were usually missing from nerve fibers in dentin. Labeling in the larger fibers was present along the axonal membrane, localized in axonal vesicles, and in nodal regions. After focal tooth injury, there is a marked loss of Cav1.2 channels in injured teeth. Immunostaining of Cav1.2 channels was lost selectively in nerve fibers and local cells of the tooth pulp within 10 min of the lesion, without loss of other Cav channel or pulpal labels. By 60 min, Cav1.2 channels in odontoblasts were detected again but at levels below controls, whereas fibroblasts were labeled well above control levels, similar to upregulation of Cav1.2 channels in astrocytes after injury. By 3 days after the injury, Cav1.2 channels were again detected in nerve fibers and immunostaining of fibroblasts and odontoblasts had returned to control levels. These findings provide new insight into the localization of Cav1.2 channels in dental pulp and sensory fibers, and demonstrate unexpected plasticity of channel distribution in response to nerve injury.

Prevalence of ROPS--equipped tractors and farm/farmer characteristics.

Data were collected on tractor safety status and the prevalence of ROPS as part of the Ohio Farm Family Health and Hazard Surveillance Program (FFHHSP) "walk-around" hazard assessments of cash grain farms in central Ohio. Principal operator (PO) characteristics thought a priori to have a possible association with ROPS utilization included age, education, percent time spent farming, total years in agriculture, and previous training in occupational injury prevention. Farm characteristics of interest were farm size, acres of cropland in use, sales value during the past 12 months, and current number of farm workers. Descriptive and logistic regression analyses were conducted to evaluate potential associations between these factors and ROPS utilization patterns. Of 1,044 tractors encountered on 306 farms, 359 (34.4%) were equipped with ROPS, 29 (9.5%) had nothing but ROPS-equipped tractors, and 117 (38.2%) did not have any ROPS-equipped tractors. The absence/presence of ROPS-equipped tractors in our sample was found to vary by several factors, and over a wide range. Results of invariable logistic regression analyses (excluding the relatively small number of tractors manufactured after 1985) indicated that younger POs with at least a high school education who spent more than half their time working in agriculture, employed three or more workers, had 500 or more acres of total farm land and cropland in use, and had a 12-month sales value exceeding $250,000 were more likely to have at least one ROPS-equipped tractor on their farms. However, time spent farming, number of workers, and the 12-month sales value were not strongly predictive in multivariable models. Although more than 20% of the POs in our sample reported having had training in occupational injury prevention, this factor had essentially no value in predicting the absence/presence of ROPS-equipped tractors on their farms. The results of this study illustrate the need for interventions to encourage ROPS retrofitting that target POs with less education and who work on smaller and less productive farms. However, the low overall ROPS utilization rates suggest that all farmers could benefit from intervention efforts.

Patterns of fluoro-gold entry into rat molar enamel, dentin, and pulp.

Permeabilities of enamel and dentin are not fully understood despite their importance for caries, restorative materials, and pulp-dentin-enamel interactions. We have found that Fluoro-Gold is useful for examining tooth permeability, and we designed studies to test the effects of aging, injury, neural function, and dentinal repair on its influx into vital rat teeth. We used fluorescence microscopy and immunocytochemistry to show that Fluoro-Gold rapidly penetrates enamel, the dentin-enamel junction, and outer dentinal acellular tubules, and then concentrates in odontoblasts, where it remains for weeks. As predicted, influx was greatest in immature teeth, and formation of reparative dentin impeded it. We expected that denervation would disrupt influx, because of neural regulation of dentinal fluid movement, but it did not. Damage to odontoblasts under injured dentin caused increased influx and efflux of Fluoro-Gold. Analysis of our data suggests that permeabilities of enamel and dentin to Fluoro-Gold are age-related, inter-dependent, and regulated by odontoblasts.

Differential roles for signal transducers and activators of transcription 5a and 5b in PRL stimulation of ERalpha and ERbeta transcription.

PRL has been shown to stimulate mRNA expression of both ERalpha and ERbeta in the rat corpus luteum and decidua of pregnancy. To investigate whether PRL may stimulate ER expression at the level of transcription and which transcription factors may mediate this stimulation, we have cloned the 5'-flanking regions of both rat ER genes. A constitutively active PRL receptor (PRL-R(CA)) stimulated both ERalpha and ERbeta promoter activity, indicating that PRL is acting to stimulate ER transcription. Putative signal transducer and activator of transcription (Stat)5 response elements were identified at -189 in the ERalpha promoter and at -330 in the ERbeta promoter. Mutation of these response elements or overexpression of dominant negative Stat5 prevented stimulation of ERalpha and ERbeta promoter activity, indicating that PRL regulation of ER expression requires both intact Stat5 binding sites as well as functional Stat5. Interestingly, either Stat5a or Stat5b could stimulate ERalpha transcription while stimulation of ERbeta occurred only in the presence of Stat5b. Through mutational analysis, a single nucleotide difference between the ERalpha and ERbeta Stat5 response elements was shown to be responsible for the lack of Stat5a-mediated stimulation of ERbeta. These findings indicate that PRL stimulation of ER expression occurs at the level of transcription and that PRL regulation of ERalpha can be mediated by either Stat5a or Stat5b, while regulation of ERbeta appears to be mediated only by Stat5b.