De-escalating aggression in acute inpatient mental health settings: a behaviour change theory-informed, secondary qualitative analysis of staff and patient perspectives.

BACKGROUND: De-escalation is often advocated to reduce harm associated with violence and use of restrictive interventions, but there is insufficient understanding of factors that influence de-escalation behaviour in practice. For the first time, using behaviour change and implementation science methodology, this paper aims to identify the drivers that will enhance de-escalation in acute inpatient and psychiatric intensive care mental health settings. METHODS: Secondary analysis of 46 qualitative interviews with ward staff (n = 20) and patients (n = 26) informed by the Theoretical Domains Framework. RESULTS: Capabilities for de-escalation included knowledge (impact of trauma on memory and self-regulation and the aetiology and experience of voice hearing) and skills (emotional self-regulation, distress validation, reducing social distance, confirming autonomy, setting limits and problem-solving). Opportunities for de-escalation were limited by dysfunctional risk management cultures/ relationships between ward staff and clinical leadership, and a lack of patient involvement in safety maintenance. Motivation to engage in de-escalation was limited by negative emotion associated with moral formulations of patients and internal attributions for behaviour. CONCLUSION: In addition to training that enhances knowledge and skills, interventions to enhance de-escalation should target ward and organisational cultures, as well as making fundamental changes to the social and physical structure of inpatient mental health wards. Psychological interventions targeting negative emotion in staff are needed to increase motivation. This paper provides a new evidence-based framework of indicative changes that will enhance de-escalation in adult acute mental health inpatient and PICU settings.

The fate of an inhaled cigarette puff in the human respiratory tract.

OBJECTIVE: Cigarette smoking can lead to a host of adverse health effects such as lung and heart disease. Increased lung cancer risk is associated with inhalation of carcinogens present in a puff of smoke. These carcinogenic compounds deposit in the lung at different sites and trigger a cascade of events leading to adverse outcomes. Understanding the site-specific deposition of various smoke constituents will inform the study of respiratory diseases from cigarette smoking. We previously developed a deposition model for inhalation of aerosol from electronic nicotine delivery systems. In this study, the model was modified to simulate inhalation of cigarette smoke consisting of soluble and insoluble tar, nicotine, and cigarette-specific constituents that are known or possible human carcinogens. MATERIALS AND METHODS: The deposition model was further modified to account for nicotine protonation and other cigarette-specific physics-based mechanisms that affect smoke deposition. Model predictions showed a total respiratory tract uptake in the lung for formaldehyde (99%), nicotine (80%), and benzo[a]pyrene (60%). RESULTS: The site of deposition and uptake depended primarily on the constituent's saturation vapor pressure. High vapor pressure constituents such as formaldehyde were preferentially absorbed in the oral cavity and proximal lung regions, while low vapor pressure constituents such as benzo[a]pyrene were deposited in the deep lung regions. Model predictions of exhaled droplet size, droplet retention, nicotine retention, and uptake of aldehydes compared favorably with experimental data. CONCLUSION: The deposition model can be integrated into exposure assessments and other studies that evaluate potential adverse health effects from cigarette smoking.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

Staff support for workplace trauma: a freedom of information act request survey for NHS trusts providing mental health care in England.

INTRODUCTION: Workplace trauma in mental health settings is defined as exposure to verbal and physical aggression, witnessing self-harm or hearing about patients' histories of abuse. Support for workplace trauma is important for staff well-being, staff retention and ultimately patient care. Assessing the extent and adequacy of staff support for workplace trauma in mental health settings is important in identifying areas of need and good practice. AIM: To determine what staff support systems are in place for workplace trauma in mental health services across England. METHODS: Freedom of Information Act requests were sent to all 57 National Health Service Trusts providing mental health care in England to identify policies on the support to mental health staff after traumatic incidents that they have experienced in the course of their clinical duties. RESULTS: Fifty-five Trusts provided usable data. Only half provided evidence of a psychologically informed incident response that went beyond a fact-finding exercise and only a fifth of Trusts used an established model for the response process. A small proportion of policies acknowledged workplace traumas related to staff discrimination on the basis of protected characteristics. CONCLUSION: There is insufficient attention to supporting mental health staff with the effects of workplace trauma.

Naturally occurring cancer-associated mutations disrupt oligomerization and activity of protein arginine methyltransferase 1 (PRMT1).

Protein arginine methylation is a posttranslational modification catalyzed by the protein arginine methyltransferase (PRMT) enzyme family. Dysregulated protein arginine methylation is linked to cancer and a variety of other human diseases. PRMT1 is the predominant PRMT isoform in mammalian cells and acts in pathways regulating transcription, DNA repair, apoptosis, and cell proliferation. PRMT1 dimer formation, which is required for methyltransferase activity, is mediated by interactions between a structure called the dimerization arm on one monomer and a surface of the Rossman Fold of the other monomer. Given the link between PRMT1 dysregulation and disease and the link between PRMT1 dimerization and activity, we searched the Catalogue of Somatic Mutations in Cancer (COSMIC) database to identify potential inactivating mutations occurring in the PRMT1 dimerization arm. We identified three mutations that correspond to W215L, Y220N, and M224V substitutions in human PRMT1V2 (isoform 1) (W197L, Y202N, M206V in rat PRMT1V1). Using a combination of site-directed mutagenesis, analytical ultracentrifugation, native PAGE, and activity assays, we found that these conservative substitutions surprisingly disrupt oligomer formation and substantially impair both S-adenosyl-L-methionine (AdoMet) binding and methyltransferase activity. Molecular dynamics simulations suggest that these substitutions introduce novel interactions within the dimerization arm that lock it in a conformation not conducive to dimer formation. These findings provide a clear, if putative, rationale for the contribution of these mutations to impaired arginine methylation in cells and corresponding health consequences.

A highly versatile fungal glucosyltransferase for specific production of quercetin-7-O-ß-D-glucoside and quercetin-3-O-ß-D-glucoside in different hosts.

Glycosylation is an effective way to improve the water solubility of natural products. In this work, a novel glycosyltransferase gene (BbGT) was discovered from Beauveria bassiana ATCC 7159 and heterologously expressed in Escherichia coli. The purified enzyme was functionally characterized through in vitro enzymatic reactions as a UDP-glucosyltransferase, converting quercetin to five monoglucosylated and one diglucosylated products. The optimal pH and temperature for BbGT are 35 ℃ and 8.0, respectively. The activity of BbGT was stimulated by Ca2+, Mg2+, and Mn2+, but inhibited by Zn2+. BbGT enzyme is flexible and can glycosylate a variety of substrates such as curcumin, resveratrol, and zearalenone. The enzyme was also expressed in other microbial hosts including Saccharomyces cerevisiae, Pseudomonas putida, and Pichia pastoris. Interestingly, the major glycosylation product of quercetin in E. coli, P. putida, and P. pastoris was quercetin-7-O-ß-D-glucoside, while the enzyme dominantly produced quercetin-3-O-ß-D-glucoside in S. cerevisiae. The BbGT-harboring E. coli and S. cerevisiae strains were used as whole-cell biocatalysts to specifically produce the two valuable quercetin glucosides, respectively. The titer of quercetin-7-O-ß-D-glucosides was 0.34 ± 0.02 mM from 0.83 mM quercetin in 24 h by BbGT-harboring E. coli. The yield of quercetin-3-O-ß-D-glucoside was 0.22 ± 0.02 mM from 0.41 mM quercetin in 12 h by BbGT-harboring S. cerevisiae. This work thus provides an efficient way to produce two valuable quercetin glucosides through the expression of a versatile glucosyltransferase in different hosts. KEY POINTS: • A highly versatile glucosyltransferase was identified from B. bassiana ATCC 7159. • BbGT converts quercetin to five mono- and one di-glucosylated derivatives in vitro. • Different quercetin glucosides were produced by BbGT in E. coli and S. cerevisiae.

A cluster randomised controlled trial of a ward-based intervention to improve access to psychologically-informed care and psychological therapy for mental health in-patients.

BACKGROUND: There is good evidence that psychological interventions improve patient well-being and independent living, but patients on acute mental health wards often do not have access to evidence-based psychological therapies which are strongly advised by NICE guidance for severe mental health problems. The overall aim of this programme of work is to increase patient access to psychological therapies on acute mental health inpatient wards. Stage one of the programme (which is complete) aimed to identify barriers and facilitators to delivering therapy in these settings through a large qualitative study. The key output of stage one was an intervention protocol that is designed to be delivered on acute wards to increase patient access to psychologically-informed care and therapy. Stage two of the programme aims to test the effects of the intervention on patient wellbeing and serious incidents on the ward (primary outcomes), patient social functioning and symptoms, staff burnout, ward atmosphere from staff and patient perspectives and cost effectiveness of the intervention (secondary outcomes). METHODS: The study is a single blind, pragmatic, cluster randomised controlled trial and will recruit thirty-four wards across England that will be randomised to receive the new intervention plus treatment as usual, or treatment as usual only. Primary and secondary outcomes will be assessed at baseline and 6-month and 9-month follow-ups, with serious incidents on the ward collected at an additional 3-month follow-up. DISCUSSION: The key output will be a potentially effective and cost-effective ward-based psychological intervention that increases patient access to psychological therapy in inpatient settings, is feasible to deliver in inpatient settings and is acceptable to patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03950388. Registered 15th May 2019. https://clinicaltrials.gov/ct2/show/NCT03950388.

Barriers to fire spread in northern Australian tropical savannas, deriving fire edge metrics from long term high-frequency fire histories.

The savannas of northern Australia are amongst the most fire-prone landscapes in the world. However, over the last fifteen years, increasing effort has been put into reducing fire extent and severity using prescribed burning strategies early in the dry season. This study seeks to improve the application of strategic fire management by providing a more detailed understanding of the landscape features that impede fire spread in Australia's tropical savannas using long-term satellite-derived fire histories. Spatial analysis of fire edges in Kakadu National Park based on fine-scale (30 m) Landsat imagery found that most fires stopped along linear edges, which were primarily associated with known features (roads, rivers and cliffs). Further analysis found linear features with the highest stopping ability covered only 13% of the park but divided the whole park into smaller containment regions. The stopping power of each feature type was found to vary according to their width and to change during the fire season, results that could help plan strategic fuel reduction burns. Similar results were seen with the lower-resolution continental-scale MODIS satellite-derived edge data. The MODIS dataset provided a means for applying fire edge analysis to support planning in areas of northern Australia that lack fine scale fire history mapping.

'Commanded to be ill, accused of being well' a lived-experience-led, qualitative investigation of service user perspectives on the impact of emotionally unstable personality disorder diagnosis on self-concept.

BACKGROUND: Emotionally unstable personality disorder (EUPD) is a mental disorder impairing health and functioning and increasing suicide risk and it is a stigmatised condition among healthcare professionals. EUPD diagnosis may significantly affect self-concept, yet no previous investigation has explicitly examined this. AIMS: To explore service user perspectives on (a) the impact of EUPD diagnosis on self-concept and (b) mediators of positive and negative impacts. METHODS: Service user-led, qualitative semi-structured interviews with n = 10 participants with EUPD. RESULTS: Perceived impacts of diagnosis on self-concept were, broadly, negative. Factors mediating between positive and negative impacts included: exposure to online stigma and public understanding, the responses of relatives, friends, intimate partners and trusted communities, and the attitudes and behaviours of healthcare staff. There were indications that recent guideline and practice developments (guidelines recommending alternatives to inpatient admissions for people with EUPD and "recovery-focused" approaches to self-harm) may have worsened inpatient staff attitudes and led to more rejecting service user experiences. CONCLUSION: Mitigating negative impacts of EUPD diagnosis on self-concept may require addressing hateful, online content related to EUPD; revisiting use of the personality disorder label; improving medical communication around diagnosis and improving practice and policy in the management of EUPD in inpatient settings.

Australian forests, megafires and the risk of dwindling carbon stocks.

Over the Austral spring and summer of 2019/20 > 7 million ha of Eucalyptus forest and woodland, including some of Australia's most carbon dense ecosystems, were burnt on the east coast of Australia. We estimated bootstrapped mean CO2 emissions of c. 0.67 Pg, with other available estimates ranging from 0.55 to 0.85 Pg. Eucalyptus forests are renowned for their ability to resist and recover from wildfire so it would be expected that emitted CO2 will be reabsorbed. The combination of drought and frequent fires is likely reducing the capacity to recover from the fire so future Australian forests may store less carbon. Broadscale prescribed burning is a widely promoted approach to reduce uncontrolled wildfires, yet the benefits for the management of carbon stores are controversial. Prescribed burning can reduce carbon losses from subsequent wildfire, yet the "carbon costs" of it may equal or outweigh the "carbon benefits" in reduced wildfire emissions. Likewise, mechanical thinning of vegetation to reduce fuel loads also carries heavy carbon costs with uncertain carbon benefits. Research involving empirical measurements, modelling and a mix of large-scale management intervention is urgently required to determine what interventions can maximise carbon storage in the face of climate change-driven fires.

A Weight-of-the-Evidence Approach for Evaluating, in Lieu of Animal Studies, the Potential of a Novel Polysaccharide Polymer to Produce Lung Overload.

The United States Environmental Protection Agency (EPA) is concerned about the respiratory effects caused by respirable particles of water-insoluble high molecular weight polymers. The EPA has proposed a tiered approach to evaluate polymer lung overload, a kinetic event. Kinetic polymer lung overload in itself is not necessarily adverse, however, inhalation of respirable particulate matter can have adverse effects (i.e., inflammation, fibrosis, etc.). If Tier I testing demonstrates that particles may reach the distal lung (i.e., a non-negligible amount of respirable particles/droplets ≤10 µm in diameter and lack of biosolubility), then animal inhalation testing in Tiers II-IV would be requested. In silico, in chemico, and in vitro alternatives should be considered versus in vivo testing for animal welfare purposes. An in chemico measure of biosolubility was used to demonstrate that a novel α-1,3-glucan polysaccharide, made by enzymatic polymerization of glucose from sucrose, is biosoluble and fits a simple exponential decay model with a half-life on the order of 66 days. The multiple-path particle dosimetry (MPPD) in silico model was used to predict lung burden for the novel α-1,3-glucan polysaccharide. MPPD was validated with measurements in rats exposed to a toner particulate and showed good agreement with lung burden measurements. A simulated 24 month rat exposure yielded 10-20 times less lung burden for the polysaccharide compared to the toner at equivalent exposure concentrations. The MPPD model was refined to include biosolubility data for the polysaccharide polymer. Data for amorphous silica were used to validate the clearance model, and the model incorporating dissolution predicted the amorphous silica lung burden within 20% of measured values. Human equivalent concentrations (HECs) were calculated for each toner rat exposure concentration. HECs were also determined for the polysaccharide at exposure concentrations yielding the same predicted internal doses as the toner. The in vitro, in chemico and in silico studies described here for the novel polysaccharide provide a useful weight of evidence approach in the absence of animal studies for the evaluation of polymer substances where polymer lung overload may be a concern.

Rapid and direct measurement of methyltransferase activity in about 30 min.

Protein arginine methylation is a widespread eukaryotic posttranslational modification that occurs to both histone and non-histone proteins. The S-adenosyl-L-methionine (AdoMet or SAM)-dependent modification is catalyzed by the protein arginine methyltransferase (PRMT) family of enzymes. In the last several years a series of both direct and indirect assay formats have been described that allow the rate of methylation to be measured. Here we provide a detailed protocol to directly measure PRMT activity using radiolabeled AdoMet, reversed-phase resin-filled pipette tips (ZipTips®) and a liquid scintillation counter. Because the ZipTips® based quantitation relies only on the straightforward separation of unreacted AdoMet from a methylated substrate, this protocol should be readily adaptable to other methyltransferases. The method is fast, simple to employ with both peptide and protein substrates, and produces very little radioactive waste.

A study on the feasibility of delivering a psychologically informed ward-based intervention on an acute mental health ward.

Acute mental health inpatient wards have been criticized for being nontherapeutic. The study aimed to test the feasibility of delivering a psychologically informed intervention in these settings. This single-arm study evaluated the feasibility of clinical psychologists delivering a ward-based psychological service model over a 6-month period on two acute mental health wards. Data were gathered to assess trial design parameters and the feasibility of gathering patient/staff outcome data. Psychologists were able to deliver key elements of the intervention. Baseline staff and patient participant recruitment targets were met. However, there was significant patient attrition at follow-up, with incorrect contact details on discharge being the primary reason. Implementation of a ward-based psychological intervention appears feasible when implemented flexibly. It is feasible to recruit staff and patient participants and to collect staff outcome measures over a 6-month period. However, greater efforts need to be taken to trace patient movement following discharge.

Evaluation of a research awareness training programme to support research involvement of older people with dementia and their care partners.

BACKGROUND: Best-practice guidelines recommend that appropriate support be provided to public contributors to facilitate their involvement in research. One form of support is research awareness training. Older people with dementia and care partners were involved in four Research User Groups (RUGs) in the UK, France, Cyprus and Greece. We delivered research awareness training (RAT) to the RUGs. The aim of this study was to evaluate the acceptability and perceived outcomes of the training from the perspective of RUG members. METHODS: At the end of each research training session, participants completed the Training Acceptability Rating Scale-section 2, which records the respondent's impressions of the training process and the outcomes of training. Participants were also invited to take part in semi-structured interviews at the end of the programme. RESULTS: Thirty-four RUG members completed the TARS-section 2 with 23 completing semi-structured interviews. Over two-thirds (67%) of participants rated their overall satisfaction with the RAT 'a great deal'. Qualitative responses indicated that participants found group work to be beneficial for learning, the structure of training activities and topics covered appropriate. The type and format of the training materials were viewed as helpful, and they valued the new knowledge gained. CONCLUSIONS: The training contents were applicable, useful and relevant to the participants' role within the research. We highlight the importance of facilitating participation by (a) fostering awareness of relevant research issues and (b) tailoring delivery of training according to the needs of the participants.

Restraint minimisation in mental health care: legitimate or illegitimate force? An ethnographic study.

Coercive practices, such as physical restraint, are used globally to respond to violent, aggressive and other behaviours displayed by mental health service users.1 A number of approaches have been designed to aid staff working within services to minimise the use of restraint and other restrictive practices. One such approach, the 'REsTRAIN Yourself' (RYS) initiative, has been evaluated in the UK. Rapid ethnography was used to explore the aspects of organisational culture and staff behaviour exhibited by teams of staff working within 14 acute admission mental health wards in the North West region of the English NHS. Findings comprise four core themes of space and place; legitimation; meaningful activity; and, therapeutic engagement that represent characteristics of daily life on the wards before and after implementation of the RYS intervention. Tensions between staff commitments to therapeutic relations and constraining factors were revealed in demarcations of ward space and limitations on availability of meaningful activities. The physical, relational and discursive means by which ward spaces are segregated prompts attention to the observed materialities of routine care. Legitimation was identified as a crucial discursive practice in the context of staff reliance upon coercion. Trauma-informed care represents a potentially alternative legitimacy.

The influence of planting size and configuration on landscape fire risk.

Revegetating cleared land with native trees and shrubs is increasingly used as a means of addressing loss of biodiversity, degraded soil and water resources and sequestration of carbon. However, revegetation also brings a potential to alter fire risk due to changing fuel types across the landscape. Previous research has found that increasing the area of revegetation does not increase the risk of fire at a landscape scale, but it remains unclear whether the design of revegetation can be optimised to minimise risk. We evaluated if size and arrangement of revegetation affects fire size and intensity within an agricultural setting using a simulation modelling approach. Three revegetation planting designs were assessed, including small (3.2 ha) dispersed plantings, small (3.2 ha) plantings clustered into one third of the landscape, and large (29.2 ha) dispersed plantings, all resulting in the same overall percentage of revegetation (approximately 10% of the landscape). We simulated fires using Phoenix Rapidfire under varying planting design, weather, surrounding pasture conditions, and fire suppression. Planting design had little effect on fire sizes across the landscape, with larger plantings resulting in slightly larger fire sizes. Fires were smaller in landscapes with all planting designs compared with current landscape patterns. There was no significant influence of planting design on fire intensity. Weather and suppression had the strongest influence on both fire size and intensity, with larger and more intense fires under extreme weather conditions, with higher adjacent pasture loads and with no simulated suppression. Management of fuel loads in the pasture surrounding revegetation, weather and suppression are far greater risk factors for fire in these landscapes than planting design.

Phe71 in Type III Trypanosomal Protein Arginine Methyltransferase 7 (TbPRMT7) Restricts the Enzyme to Monomethylation.

Protein arginine methyltransferase 7 (PRMT7) is unique within the PRMT family as it is the only isoform known to exclusively make monomethylarginine (MMA). Given its role in epigenetics, the mechanistic basis for the strict monomethylation activity is under investigation. It is thought that PRMT7 enzymes are unable to add a second methyl group because of steric hindrance in the active site that restricts them to monomethylation. To test this, we probed the active site of trypanosomal PRMT7 (TbPRMT7) using accelerated molecular dynamics, site-directed mutagenesis, kinetic, binding, and product analyses. Both the dynamics simulations and experimental results show that the mutation of Phe71 to Ile converts the enzyme from a type III methyltransferase into a mixed type I/II, that is, an enzyme that can now perform dimethylation. In contrast, the serine and alanine mutants of Phe71 preserve the type III behavior of the native enzyme. These results are inconsistent with a sterics-only model to explain product specificity. Instead, molecular dynamics simulations of these variants bound to peptides show hydrogen bonding between would-be substrates and Glu172 of TbPRMT7. Only in the case of the Phe71 to Ile mutation is this interaction between MMA and the enzyme maintained, and the geometry for optimal SN2 methyl transfer is obtained. The results of these studies highlight the benefit of combined computational and experimental methods in providing a better understanding for how product specificity is dictated by PRMTs.

Patient perspectives on barriers and enablers to the use and effectiveness of de-escalation techniques for the management of violence and aggression in mental health settings.

AIM: Investigate patient perspectives on barriers and enablers to the use and effectiveness of de-escalation techniques for aggression in mental health settings. BACKGROUND: De-escalation techniques are the recommended first-line intervention for the management of aggression in mental health settings internationally, yet use of higher risk restrictive practices persists. This indicates de-escalation techniques are not used at optimum frequency and/or there are important factors limiting their use and effect. DESIGN: Descriptive qualitative research using semi-structured interviews and Framework Analysis. METHODS: Inpatient interviews (N = 26) exploring staff, patient and environmental factors influencing the use and effectiveness of staff de-escalation were conducted mid-2014. Three service user researchers led analysis. RESULTS: Data were synthesized in three deductive themes relating to staff, patient and environmental influences on the use and effectiveness of de-escalation techniques. The dominant view was that restrictive practices, rather than de-escalation techniques, are used in response to escalating patient behaviour. Under-use of de-escalation techniques was attributed to: lack of staff reflection on culture and practice and a need to retain control/dominance over patients. Ward rules, patient factors and a lack of staff respect for patients diluted their effectiveness. Participants identified a systematic process of de-escalation, rule subversion, reduced social distance and staff authenticity as enablers of effective de-escalation. CONCLUSION: This study investigated patient perspectives on staff, patient and environmental influences on the use and effectiveness of de-escalation techniques. Our framework of barriers and enablers provides indicators of organizational/behaviour change targets for interventions seeking to reduce violence and restrictive practices through enhanced de-escalation techniques.

Suppression resource decisions are the dominant influence on containment of Australian forest and grass fires.

Fire agencies aim to contain wildfires before they impact on life, property and infrastructure and to reduce the risk of damage to the environment. Despite the large cost of suppression, there are few data on the success of suppression efforts under varying weather, fuel and resource scenarios. We examined over 2200 forest and 4600 grass fires in New South Wales, Australia to determine the dominant influences on the containment of wildfires. A random forest modelling approach was used to analyse the effect of a range of human and environmental factors. The number of suppression resources per area of fire were the dominant influence on the containment of both forest and grass fires. As fire weather conditions worsened the probability of containment decreased across all fires and as fuel loads and slope increased the probability of containment decreased for forest fires. Environmental controls limit the effectiveness of wildfire management. However, results suggest investment in suppression resources and strategic fuel management will increase the probability of containment.

Effects of Formulation Variables on Lung Dosimetry of Albuterol Sulfate Suspension and Beclomethasone Dipropionate Solution Metered Dose Inhalers.

The performance of pressurized metered dose inhalers (MDIs) is affected by formulation and device variables that impact delivered dose, aerodynamic particle size distribution, and consequently lung deposition and therapeutic effect. Specific formulation variables of relevance to two commercially available products-Proventil® HFA [albuterol sulfate (AS) suspension] and Qvar® [beclomethasone dipropionate (BDP) solution]-were evaluated to determine their influence on key performance attributes measured experimentally with in vitro cascade impaction studies. These commercial MDIs, utilized as model systems, provided mid-points for a design of experiments (DoE) plan to manufacture multiple suspension and solution MDI formulations. The experimental results were utilized as input variables in a computational dosimetry model to predict the effects of MDI formulation variables on lung deposition. For the BDP solution DoE MDIs, increased concentrations of surfactant oleic acid (0-2% w/w) increased lung deposition from 24 to 46%, whereas changes in concentration of the cosolvent ethanol (7-9% w/w) had no effect on lung deposition. For the AS suspension DoE MDIs, changes in oleic acid concentration (0.005-0.25% w/w) did not have significant effects on lung deposition, whereas lung deposition decreased from 48 to 26% as ethanol concentration increased from 2 to 20% w/w, and changes in micronized drug volumetric median particle size distribution (X50, 1.4-2.5 µm) increased deposition in the tracheobronchial airways from 5 to 11%. A direct correlation was observed between fine particle fraction and predicted lung deposition. These results demonstrate the value of using dosimetry models to further explore relationships between performance variables and lung deposition.