Impacts of radiation exposure on the bacterial and fungal microbiome of small mammals in the Chernobyl Exclusion Zone.

Environmental impacts of the 1986 Chernobyl Nuclear Power Plant accident are much debated, but the effects of radiation on host microbiomes have received little attention to date. We present the first analysis of small mammal gut microbiomes from the Chernobyl Exclusion Zone in relation to total absorbed dose rate, including both caecum and faeces samples. We provide novel evidence that host species determines fungal community composition, and that associations between microbiome (both bacterial and fungal) communities and radiation exposure vary between host species. Using ambient versus total weighted absorbed dose rates in analyses produced different results, with the latter more robust for interpreting microbiome changes at the individual level. We found considerable variation between results for faecal and gut samples of bank voles, suggesting faecal samples are not an accurate indicator of gut composition. Associations between radiation exposure and microbiome composition of gut samples were not robust against geographical variation, although we identified families of bacteria (Lachnospiraceae and Muribaculaceae) and fungi (Steccherinaceae and Strophariaceae) in the guts of bank voles that may serve as biomarkers of radiation exposure. Further studies considering a range of small mammal species are needed to establish the robustness of these potential biomarkers.

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I-II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5-34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I-III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.

Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate.

The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1nu and NOD/SCID mice and treated with intratumoral injection of 30 µg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1nu mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.

Hospital-acquired pressure injuries: Are they accurately reported? A prospective descriptive study in a large tertiary hospital in Australia.

AIM: The aim of this study was to (1) examine the reasons for the increased incidence of hospital-acquired pressure injuries (HAPIs) reported in the Incident Information Management System (IIMS), and (2) gain feedback from nurses regarding HAPI being reported in the IIMS at one tertiary hospital in Australia. MATERIALS AND METHODS: This prospective descriptive study included a review of patients with a reported HAPI from July 2015 to June 2016. Patient assessment and semi-structured interviews with nurses were conducted. Interview data were anonymised and content thematically analysed. RESULTS: Data were collected on 417 patients who were reported to have a HAPI; of these, 363 patients were clinically assessed. 69.7% (253/363) were inaccurately reported in the IIMS, based on stage, location, not a true pressure injury or not hospital-acquired. A high number of patients (176/363, 48.5%) were found to have various skin conditions that were not HAPIs. Three themes were identified from the interviews: (1) meeting the mandated reporting requirements; (2) incident reporting and communication; (3) difficulties documenting aetiology. CONCLUSION: This study identified inaccuracies in diagnosing, classifying and reporting pressure injuries. Nurses described barriers and challenges to classifying and reporting HAPIs. Inaccurate reporting can lead to incorrect conclusions especially when reported data alone is relied upon for patient treatment, benchmarking and analysis. Guidelines are needed at a national and international level to support the quality of clinical assessment, reporting and documentation. Findings from this study have led to a new approach to patient assessment and to minimise errors in incident reporting at this organisation.

Knowledge and Attitudes of Nurses Toward Pressure Injury Prevention: A Cross-Sectional Multisite Study.

PURPOSE: The purpose of the study was to examine the knowledge and attitudes of nurses on pressure injury prevention and determine if there was a relationship between knowledge, attitude, and years of experience following an unexplained increase in reported hospital-acquired pressure injuries across 1 health district in Sydney, Australia. DESIGN: Multisite cross-sectional study. SUBJECTS AND SETTING: Registered and enrolled nurses working in acute, medical, and rehabilitation units in 4 hospitals and 5 community health centers across a local health district. METHODS: Using a modified version of the Pressure Ulcer Knowledge Test and the Staff Attitude Scale, nurses were invited to complete the survey online or on paper. RESULTS: A total of 3123 surveys were distributed and 998 were returned yielding a response rate of 32%. Approximately one-third of nurse respondents who participated in the survey had been practicing for 5 to 10 years. Almost 80% of participants scored 33/47 or more (70% or more correct) on the knowledge survey; the mean score was 35.21. The mean score for the attitudes test was 44.43 ± 4.77, out of 55 (80.7%), indicating a positive attitude toward pressure injury prevention. There was a significant positive correlation between nurses' years of experience and attitudes, but there was no correlation between years of experience and knowledge. Knowledge and attitudes were also significantly positively correlated. CONCLUSIONS: Nurses had sound knowledge and held positive attitudes toward pressure injury prevention. Positive attitudes were associated with greater time spent in the workforce. Additional research is required to examine relationships between knowledge of and attitude toward pressure injury prevention and clinical practice. Further research is also needed to determine if improving knowledge and attitudes results in a sustained reduction of hospital-acquired pressure injuries.

Incontinence, Incontinence-Associated Dermatitis, and Pressure Injuries in a Health District in Australia: A Mixed-Methods Study.

PURPOSE: This purpose of this study was to measure the prevalence of incontinence, incontinence-associated dermatitis (IAD), and pressure injuries (PIs) in a local health district in Australia. We also aimed to determine associated evidence-into-practice gaps. DESIGN: Multisite mixed-methods study. SUBJECTS AND SETTINGS: The sample comprised 250 adult patients in 12 units across 4 hospitals; their mean age was 73 years. Nurses caring for the patient at the time of the audit were questioned on nursing practice for patients with incontinence. METHODS: A 2-page audit tool was developed and used to capture demographic data, continence and mobility status, IAD and PI, incontinence products, nursing practice observations, and nurses' comments. Each patient was assessed by 2 senior nurses. Quantitative analysis included descriptive statistics and bivariate analysis using a χ test to examine the association between mobility and incontinence and a Fisher exact test to examine the association between IAD and PI. Content analysis was used to analyze qualitative data and develop themes. RESULTS: Almost half of patients had incontinence (n = 111/250), 20.7% of patients with incontinence (n = 23/111) had IAD, and 6.3% (n = 7/111) had hospital-acquired PI. There was a significant association between incontinence and mobility, and between IAD and PIs. In addition, 22.3% of patients who were continent (31/139) were wearing an incontinence product. Analysis of qualitative data found that both incontinence management and language used to refer to incontinence pads were incompatible with current best practices. CONCLUSION: The prevalence of incontinence among patients observed in this study was similar to rates reported internationally, but the prevalence of IAD was slightly lower. The association between IAD and PIs, as well as incontinence and mobility, was statistically and clinically significant. Nurses commonly used interventions with little or no evidence. Hospitals should put measures in place to improve nurses' knowledge of incontinence, IAD, and PI practices.

Education and training in radioecology during the EU-COMET project-successes and suggestions for the future.

The 2014 Strategic Research Agenda (SRA) for Radioecology identified the key challenge in education and training (E&T) as being 'to maintain and develop a skilled workforce in Europe and world-wide, through university candidates and professionals trained within radioecology' since 'scientific research in radioecology and application of that knowledge … requires scientists and workers with adequate competence and appropriate skills.' Radioecology is a multidisciplinary science and E&T is needed by both students and professionals within research, industry and radiation protection. In order to address these needs, the EU COMET project has developed an E&T web platform and arranged a number of field courses, training courses, PhD and MSc courses, refresher courses and workshops, drawing on the COMET consortium to assemble relevant experts. In addition, COMET has been engaged in discussions with stakeholders for more long-term solutions to maintain the sustainability of radioecology E&T after the end of the project. Despite much progress in some areas, many of the challenges outlined in the 2014 SRA remain, mainly due to the lack of sustainable dedicated funding. Future plans within the ALLIANCE radioecology platform and the CONCERT-European Joint Programme for the Integration of Radiation Protection Research must urgently address this lack of sustainability if radioecological competence is to be maintained in Europe.

Medical device-related pressure injuries: An exploratory descriptive study in an acute tertiary hospital in Australia.

AIM: To examine and explore medical device-related pressure injuries in an 800-bed tertiary hospital. MATERIALS AND METHODS: An exploratory descriptive study design was employed. A prospective review of all data on reported hospital-acquired pressure injuries was conducted on a weekly basis from July 2015 to August 2016. This included a patient assessment and medical record review as well as brief semi-structured interviews with nurses. RESULTS: The overall incidence of medical device-related pressure injuries was 27.9% (50/179) with the majority (68%, 34/50) occurring in intensive care. The most common cause of a medical device-related pressure injury was oxygen tubing behind ears (n = 21) and endotracheal tubes (n = 13). Nurses were unaware of the implications of medical devices in contact with the skin and patient medical records did not present a valuable source of information in relation to pressure injury prevention. CONCLUSION: Medical device-related pressure injuries were represented in 27.9% of our entire patient cohort; primarily occurring on the ear from oxygen tubing and on the mouth from endotracheal tubes in patients in intensive care. Additional support, education and monitoring for nurses at a local level on the prevention of medical device-related pressure injuries is necessary to prevent their occurrence. Furthermore, consensus on the classification and reporting of medical device-related pressure injuries is still in development, making reporting and monitoring challenging. Medical device-related pressure injuries are a continuing clinical issue that require further exploration.

Evaluation of a nurse practitioner-led extended hours mental health liaison nurse service based in the emergency department.

OBJECTIVE: To evaluate a nurse practitioner (NP)-led extended hours mental health liaison nurse (MHLN) service based in the emergency department (ED) of an inner city teaching hospital in Sydney and to explicate a model of care that is transferable across a broad range of ED settings, both in metropolitan and rural contexts. METHODS: This mixed-methods evaluation encompassed descriptive data on ED mental health presentations, quantifying waiting times for MHLN involvement and interviews with MHLN team members at the commencement of the evaluation and 12 months later. Interviews were also conducted with a snapshot of ED patients, and a sample of ED and psychiatry staff. RESULTS: The expanded MHLN service was rapidly incorporated into the ED structure, enthusiastically endorsed by ED patients and highly valued by staff and the organisation. The MHLN team saw 55% of referred patients within the first hour of arrival (frequently before medical assessment), thereby initiating and expediting co-ordination of care at an early stage of the ED process. CONCLUSIONS: An NP-led extended hours MHLN team based in the ED provides prompt and effective access to specialised mental health care for people with 'undifferentiated health problems', and removes a significant workload from nursing and medical staff. Embedding the NP-led MHLN service within the ED structure was pivotal to the success and sustainability of this model of care.

Long-term outcomes in advanced anterior skull base malignancy: a single quaternary institution experience.

BACKGROUND: Advanced skull base malignancies are a heterogenous subset of head and neck cancers, and management is often complex. In recent times, there has been a paradigm shift in surgical technique and the advent of novel systemic options. Our goal was to analyse the long-term outcomes of a single quaternary head and neck and skull base service. METHODS: A retrospective review of 127 patients with advanced anterior skull base malignancies that were treated at our institution between 1999 and 2015 was performed. Multiple variables were investigated to assess their significance on 5 and 10-year outcomes. RESULTS: The mean age was 60.9 (± 12.6 SD). Sixty-four percent were males and 36% were females. Ninety percent of patients had T4 disease. Median survival time was 133 months. The 5-year overall survival (OS) was 66.2%, disease-specific survival (DSS) was 74.7%, and recurrence-free survival (RFS) was 65.0%. The 10-year OS was 55.1%, DSS was 72.1%, and RFS was 53.4%. Histological type and margin status significantly affected OS & DSS. CONCLUSION: Surgical management of advanced skull base tumours has evolved over the last few decades at our institution with acceptable survival outcomes and complication rates. Histological diagnosis and margin status are the main predictors of survival. The addition of neoadjuvant systemic agents in current trials may improve outcomes.

Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

Current ionising radiation doses in the Chernobyl Exclusion Zone do not directly impact on soil biological activity.

Although soil organisms are essential for ecosystem function, the impacts of radiation on soil biological activity at highly contaminated sites has been relatively poorly studied. In April-May 2016, we conducted the first largescale deployment of bait lamina to estimate soil organism (largely soil invertebrate) feeding activity in situ at study plots in the Chernobyl Exclusion Zone (CEZ). Across our 53 study plots, estimated weighted absorbed dose rates to soil organisms ranged from 0.7 µGy h-1 to 1753 µGy h-1. There was no significant relationship between soil organism feeding activity and estimated weighted absorbed dose rate. Soil biological activity did show significant relationships with soil moisture content, bulk density (used as a proxy for soil organic matter) and pH. At plots in the Red Forest (an area of coniferous plantation where trees died because of high radiation exposure in 1986) soil biological activity was low compared to plots elsewhere in the CEZ. It is possible that the lower biological activity observed in the Red Forest is a residual consequence of what was in effect an acute high exposure to radiation in 1986.

Wildfires in the Chornobyl exclusion zone-Risks and consequences.

Following the 1986 Chornobyl accident, an area approaching 5000 km2 surrounding the nuclear plant was abandoned, creating the Chornobyl exclusion zone (CEZ). Although this area likely contains the most radioactive terrestrial ecosystem on earth, the absence of humans and associated activities for nearly 35 years since the accident has resulted in increases in wildlife numbers. Both the Belarussian and Ukrainian components of the CEZ are now designated as nature reserves; together they form one of Europe's largest protected areas and have been described as an iconic example of rewilding. Forests and former agricultural land (now scrub) dominate the CEZ and wildfires are an annual event. In April 2020, the CEZ suffered its most widespread fires to date when greater than 800 km2 of the 2600 km2 Ukrainian portion of the CEZ was burnt. Large-scale fires in the CEZ have implications for wildlife, as they do elsewhere, but they also pose additional radioecological and radiological protection questions. We discuss the implications of wildfires in the CEZ, considering effects on wildlife and changes in radionuclide mobility. We also demonstrate that the risk to firefighters and the wider public from the inhalation of radionuclides in smoke resulting from fires in the CEZ is likely to be low. However, further experimental and modeling work to evaluate potential doses to firefighters from inhaled radioactive particles would be valuable, not least for reassurance purposes. Integr Environ Assess Manag 2021;17:1141-1150 © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Whole-body to tissue concentration ratios for use in biota dose assessments for animals.

Environmental monitoring programs often measure contaminant concentrations in animal tissues consumed by humans (e.g., muscle). By comparison, demonstration of the protection of biota from the potential effects of radionuclides involves a comparison of whole-body doses to radiological dose benchmarks. Consequently, methods for deriving whole-body concentration ratios based on tissue-specific data are required to make best use of the available information. This paper provides a series of look-up tables with whole-body:tissue-specific concentration ratios for non-human biota. Focus was placed on relatively broad animal categories (including molluscs, crustaceans, freshwater fishes, marine fishes, amphibians, reptiles, birds and mammals) and commonly measured tissues (specifically, bone, muscle, liver and kidney). Depending upon organism, whole-body to tissue concentration ratios were derived for between 12 and 47 elements. The whole-body to tissue concentration ratios can be used to estimate whole-body concentrations from tissue-specific measurements. However, we recommend that any given whole-body to tissue concentration ratio should not be used if the value falls between 0.75 and 1.5. Instead, a value of one should be assumed.

Transfer of natural and anthropogenic radionuclides to ants, bryophytes and lichen in a semi-natural ecosystem.

Few data are available to quantify the transfer of both natural and anthropogenic radionuclides to detritivorous invertebrates to facilitate estimation of the internal dose to such biota in models used to assess radiation exposure. To enhance the available data, activity concentrations of (137)Cs, (40)K, (90)Sr, (239 + 240)Pu, (241)Am, (235)U and (238)U were measured in ants (Formicidae) and corresponding undisturbed soil collected from the Zlatibor mountain in Serbia and ant/soil concentration ratios (CR) calculated. The (241)Am concentration ratios for ants were fourfold higher than those calculated for ants in a previous study whereas they are similar to the more numerous data previously reported for a range of detritivorous invertebrates in other studies. CR values for (137)Cs in ants were similar to the few other reported values and slightly lower than those for a range of detritivorous invertebrates. Those for (239 + 240)Pu were slightly higher than those for ants in two other studies but they were close to upper limit of a range of data reported for detritivorous invertebrates. All the CR values will be included in a future revision of the ERICA Tool database and will particularly improve the information available for uranium.

Expression of innate resistance factors in mammary secretion from periparturient dairy heifers and their association with subsequent infection status.

Mastitis in dairy heifers in the peripartum period is a common and costly problem for producers, and mammary innate resistance is of key importance in defense of the gland from bacterial invasion. A prospective observational study was undertaken in 97 dairy heifers to measure associations between expression of eight innate resistance factors in mammary secretions collected from the same animals within 14 days prior to calving and at calving, and intramammary infection (IMI) status at calving, and to describe changes in expression of these factors over time. Relative expression (RE) of eight candidate resistance mediator genes from cells from intramammary secretion was measured by quantitative real time polymerase chain reaction. Glands which were IMI-free pre-calving and did not develop a new IMI had significantly higher RE of molecule possessing ankyrin-repeat (MAIL) and beta defensin (Bdef) genes compared to glands which subsequently did develop a new IMI. Also, Bdef RE increased up to the day of calving in glands that did not develop a new IMI, but was unresponsive in glands that did develop a new IMI. Relative expression of complement 5 alpha receptor, interleukin 1beta and interleukin 8 increased in glands that did develop a new IMI. Serum amyloid A3 and toll-like receptor 2 RE increased in all glands up to the day of calving. Transforming growth factor beta RE was not associated with new infection status or time relative to calving. These findings support further investigation of function and gene polymorphisms of MAIL and Bdef as potential markers of mastitis resistance in dairy heifers.

CXCR4 and PD-1 Expression in Head and Neck Cancer with Perineural Spread.

Background Perineural spread (PNS) is a marker of aggressiveness and has been shown to occur in cranial nerves due to advanced mucosal and cutaneous head and neck cancer. Receptors CXC chemokine receptor 4 (CXCR4) and programmed cell death-1 (PD-1) have been shown to be overexpressed in a variety of cancers with PNS, with the inhibition of these pathways offering a potential future treatment. Methods Retrospective immunohistochemical staining for the CXCR4 and PD-1 receptors was performed on 28 head and neck specimens that demonstrated PNS from January 2017 to August 2017, at Royal Brisbane and Women's Hospital, Brisbane, Australia. Results CXCR4 staining was positive in 52 and 60% of the squamous cell carcinoma (SCC) and adenoid cystic carcinoma PNS specimens, respectively. Cutaneous SCC tumors with no PNS stained positively in 33%. No significant staining for PD-1 in peritumoral lymphocytes or tumor specimens was seen. Conclusion CXCR4 is overexpressed in advanced skin cancer and head and neck tumors that demonstrated PNS to large cranial nerves. Overall, these results provide strong support for using CXCR4 as a biomarker and further investigation of immunotherapeutic agents that could inhibit tumor progression via targeting CXCR4 expression.

Nurse confidence in gynaecological oncology practice and the evaluation of a professional development module.

BACKGROUND: A tertiary-based education program on gynaecological oncology was attended by 62 registered nurses (RN). AIMS: The program aimed to update nurses' knowledge, improve skills and ability to manage common situations and to assess program efficacy. DESIGN: Evaluation framework with specifically designed pre-post questionnaire about program content and nurse confidence. METHOD: RN interested in gynaecological oncology were invited to attend. Nurses rated their confidence about gynaecological oncology skills one week prior to the program, immediately post-course, 3 months post and 12 months post. Speaker presentations were evaluated immediately post-course. RESULTS: Participants indicated improved confidence immediately after participating in the course (z = -6.515, p < .001); whilst confidence subsequently declined and stabilised up to 12 months post-course, it still remained significantly higher than before the course: 3 months post- (z = -5.284, p < .001) and 12 months post- (z = -4.155, p < .001). CONCLUSIONS: Results support the value of continuing professional education for improving nurse confidence in the gynaecological oncology setting.