Olokizumab plus methotrexate: safety and efficacy over 106 weeks of treatment.

OBJECTIVE: To report long-term safety and tolerability of olokizumab (OKZ) in combination with methotrexate (MTX) in subjects with active rheumatoid arthritis (RA), using pooled data from three randomised clinical trials (RCT) followed by open-label extension (OLE) study. METHODS: Cumulative data from three phase 3 core trials and their OLE were analysed. Safety variables assessed included treatment-emergent adverse events (AEs), serious AEs (SAEs), AEs of special interest and laboratory results. Efficacy assessments included ACR20/50/70 responses, Disease Activity Score 28 (C-reactive protein) <3.2, CDAI remission and low disease activity (LDA), SDAI remission and LDA, HAQ-DI decrease of 0.22 unit and Boolean 2.0 remission. RESULTS: A total of 2304 patients received OKZ in combination with MTX either once every 2 weeks or once every 4 weeks. Event rates per 100 patient-years in OKZ every 2 weeks and OKZ every 4 weeks, respectively, were 9.57 and 9.13 for SAEs; 2.95 and 2.34 for serious infections; 0.09 and 0.05 for gastrointestinal perforations; 0.58 and 0.83 for major adverse cardiovascular events; and 0.45 and 0.50 for malignancies. No increase in the rate of any AE was observed over 106 weeks of treatment. The evaluation of laboratory variables demonstrated the expected changes, like neutropenia, elevation of liver enzymes and blood lipids. Clinical response rates remained stable during the OLE. CONCLUSION: The long-term safety and tolerability of OKZ in combination with MTX remained stable. The efficacy of OKZ was maintained through week 106. These findings support OKZ as a treatment option for patients with active RA.

An anti-mitotic compound, (+)-6-tuliposide A, isolated from the Canadian glacier lily, Erythronium grandiflorum.

The Canadian prairie ecosystem is subjected to abiotic and biotic conditions that induce plants to produce secondary metabolites that affect mammalian physiology. Extracts prepared from certain plant species native to Canadian prairie and montane cordillera ecosystems have previously been shown to have anti-mitotic activity on human cancer cell lines. In this study, we investigated the glacier lily, Erythronium grandiflorum (Liliaceae), in which the species was the most phylogenetically distant from Asteraceae and had anti-mitotic activity. When added to cell lines, E. grandiflorum extracts induced rounded cell morphology and arrested cells in the G2/M phase of the cell cycle. Of the cells that displayed a rounded phenotype, all were positive for phospho-histone H3 and contained a distorted mitotic spindle. This anti-mitotic activity was distinct from that of the compound colchicine, which has been previously isolated from the Liliaceae family. By biology-guided fractionation, we isolated the natural product (+)-6-tuliposide A and are the first to report its anti-mitotic activity. These results reveal a chemical motif in secondary metabolites and expand the range of Canadian prairie plants with anti-mitotic activity that can become new scientific tools or used in the development of anti-proliferative medicines.

GUT MICROBIOME DIVERSITY OF THREE RHINOCEROS SPECIES IN EUROPEAN ZOOS.

The wild rhinoceros populations have declined drastically in the past decades because the rhinoceros are heavily hunted for their horns. Zoological institutions aim to conserve rhinoceros populations in captivity, but one of the challenges of ex situ conservation is to provide food sources that resemble those available in the wild. Considering that the mammalian gut microbiota is a pivotal player in their host's health, the gut microbiota of rhinoceros may also play a role in the bioavailability of nutrients. Therefore, this study aims to characterize the fecal microbiome composition of grazing white rhinoceros (WR; Ceratotherium simum) and greater one-horned rhinoceros (GOHR; Rhinoceros unicornis) as well as the browsing black rhinoceros (BR; Diceros bicornis) kept in European zoos. Over the course of 1 yr, 166 fecal samples in total were collected from 9 BR (n = 39), 10 GOHR (n = 56), and 14 WR (n = 71) from 23 zoological institutions. The bacterial composition in the samples was determined using 16S rRNA gene Illumina sequencing. The fecal microbiomes of rhinoceros clustered by species, with BR clustering more distantly from GOHR and WR. Furthermore, the data report clustering of rhinoceros microbiota according to individual rhinoceros and institutional origin, showing that zoological institutions play a significant role in shaping the gut microbiome of rhinoceros species. In addition, BR exhibit a relatively higher microbial diversity than GOHR and WR. BR seem more susceptible to microbial gut changes and appear to have a more diverse microbiome composition among individuals than GOHR and WR. These data expand on the role of gut microbes and can provide baseline data for continued efforts in rhinoceros conservation and health status.

Hydraulic modeling of the Periyar River using HEC-RAS: unraveling flow dynamics.

The Periyar River, a vital component of Kerala's ecosystem in India, serves as a lifeline supporting agriculture, hydropower generation, and ecological equilibrium. This study adopts a multifaceted approach to address critical challenges in the Periyar basin, with a primary focus on flood mitigation due to the region's susceptibility to devastating floods. Covering a length of 67.85 km, the study intricately segments the Periyar River into distinct reaches for a comprehensive steady flow analysis, considering factors such as seasonal monsoon fluctuations, diverse catchment topography, and human-induced alterations. Utilizing advanced modeling techniques, particularly HEC-RAS software, the study effectively predicts and simulates shifts in hydraulic behavior. The results, including velocity plots and cross-sectional maps, offer accurate insights into critical parameters, enabling the identification of areas with high velocity occurrence. This information proves instrumental in making informed decisions for the construction of river restoration structures, crucial for mitigating the impact of floods. The study's findings contribute valuable tools for future forecasting and sustainable management of the Periyar River, addressing the complex interplay of natural and anthropogenic factors.

Road Traffic Emissions Lead to Much Enhanced New Particle Formation through Increased Growth Rates.

New particle formation (NPF) is a major source of atmospheric aerosol particles, including cloud condensation nuclei (CCN), by number globally. Previous research has highlighted that NPF is less frequent but more intense at roadsides compared to urban background. Here, we closely examine NPF at both background and roadside sites in urban Central Europe. We show that the concentration of oxygenated organic molecules (OOMs) is greater at the roadside, and the condensation of OOMs along with sulfuric acid onto new particles is sufficient to explain the growth at both sites. We identify a hitherto unreported traffic-related OOM source contributing 29% and 16% to total OOMs at the roadside and background, respectively. Critically, this hitherto undiscovered OOM source is an essential component of urban NPF. Without their contribution to growth rates and the subsequent enhancements to particle survival, the number of >50 nm particles produced by NPF would be reduced by a factor of 21 at the roadside site. Reductions to hydrocarbon emissions from road traffic may thereby reduce particle numbers and CCN counts.

Regional impact assessment of air quality improvement: The air quality lifecourse assessment tool (AQ-LAT) for the West Midlands combined authority (WMCA) area.

Poor air quality is the largest environmental health risk in England. In the West Midlands, UK, ∼2.9 million people are affected by air pollution with an average loss in life expectancy of up to 6 months. The 2021 Environment Act established a legal framework for local authorities in England to develop regional air quality plans, generating a policy need for predictive environmental impact assessment tools. In this context, we developed a novel Air Quality Lifecourse Assessment Tool (AQ-LAT) to estimate electoral ward-level impacts of PM2.5 and NO2 exposure on outcomes of interest to local authorities, namely morbidity (asthma, coronary heart disease (CHD), stroke, lung cancer), mortality, and associated healthcare costs. We apply the Tool to assess the health economic burden of air pollutant exposure and estimate benefits that would be generated by meeting WHO 2021 Global Air Quality Guidelines (AQGs) (annual average concentrations) for NO2 (10 µg/m3) and PM2.5 (5 µg/m3) in the West Midlands Combined Authority Area. All West Midlands residents live in areas which exceed WHO AQGs, with 2070 deaths, 2070 asthma diagnoses, 770 CHD diagnoses, 170 lung cancers and 650 strokes attributable to air pollution exposure annually. Reducing PM2.5 and NO2 concentrations to WHO AQGs would save 10,700 lives reducing regional mortality by 1.8%, gaining 92,000 quality-adjusted life years (QALYs), and preventing 20,500 asthma, 7400 CHD, 1400 lung cancer, and 5700 stroke diagnoses, with economic benefits of £3.2 billion over 20 years. Significantly, we estimate 30% of QALY gains relate to reduced disease burden. The AQ-LAT has major potential to be replicated across local authorities in England and applied to inform regional investment decisions.

Direct Measurements of Covalently Bonded Sulfuric Anhydrides from Gas-Phase Reactions of SO3 with Acids under Ambient Conditions.

Sulfur trioxide (SO3) is an important oxide of sulfur and a key intermediate in the formation of sulfuric acid (H2SO4, SA) in the Earth's atmosphere. This conversion to SA occurs rapidly due to the reaction of SO3 with a water dimer. However, gas-phase SO3 has been measured directly at concentrations that are comparable to that of SA under polluted mega-city conditions, indicating gaps in our current understanding of the sources and fates of SO3. Its reaction with atmospheric acids could be one such fate that can have significant implications for atmospheric chemistry. In the present investigation, laboratory experiments were conducted in a flow reactor to generate a range of previously uncharacterized condensable sulfur-containing reaction products by reacting SO3 with a set of atmospherically relevant inorganic and organic acids at room temperature and atmospheric pressure. Specifically, key inorganic acids known to be responsible for most ambient new particle formation events, iodic acid (HIO3, IA) and SA, are observed to react promptly with SO3 to form iodic sulfuric anhydride (IO3SO3H, ISA) and disulfuric acid (H2S2O7, DSA). Carboxylic sulfuric anhydrides (CSAs) were observed to form by the reaction of SO3 with C2 and C3 monocarboxylic (acetic and propanoic acid) and dicarboxylic (oxalic and malonic acid)-carboxylic acids. The formed products were detected by a nitrate-ion-based chemical ionization atmospheric pressure interface time-of-flight mass spectrometer (NO3--CI-APi-TOF; NO3--CIMS). Quantum chemical methods were used to compute the relevant SO3 reaction rate coefficients, probe the reaction mechanisms, and model the ionization chemistry inherent in the detection of the products by NO3--CIMS. Additionally, we use NO3--CIMS ambient data to report that significant concentrations of SO3 and its acid anhydride reaction products are present under polluted, marine and polar, and volcanic plume conditions. Considering that these regions are rich in the acid precursors studied here, the reported reactions need to be accounted for in the modeling of atmospheric new particle formation.

Examining the impact of a paediatric trauma family support service on the quality of life of injured children: A longitudinal cohort study.

PURPOSE: We describe and evaluate the introduction of a trauma family support service (TFSS) in an Australian tertiary paediatric hospital. DESIGN AND METHODS: A longitudinal mixed-methods cohort study evaluated the effectiveness of the TFSS on quality of life. PedsQL4.0 and EuroQol 5D-Y scores were collected at 6 and 12 months at intervention and non-intervention sites and outcomes were compared using a two-sample t-test. Qualitative data from field notes collected during the administration of the quality-of-life measures were analysed using inductive content analysis. Data were integrated during the interpretation of results to expand and strengthen findings. RESULTS: Data from 192 children were collected (intervention site: 104, control site: 88). Significant increases were seen in the PedsQL and EQ-5D-Y scores at the intervention site compared to the control site at both timepoints, indicating an increase in overall health related quality of life. Two main categories were generated from the qualitative analysis: "Psychosocial impact of trauma" and "Access to psychosocial services." CONCLUSIONS: The introduction of a dedicated family support service after paediatric injury improved well-being up to 12 months post injury. PRACTICE IMPLICATIONS: Healthcare providers should emphasise dedicated family support services for paediatric trauma patients, focusing on their psychosocial needs and ensuring access to suitable resources. Paediatric nurses are a major part of this service and should contribute to future research, co-designing and implementing these improved family support services to better serve families affected by paediatric trauma.

Barriers and co-designed strategies for the implementation of negative pressure wound therapy in acute pediatric burn care in Australia: A mixed method study.

PURPOSE: Pediatric burn injuries are a global clinical issue causing significant morbidity. Early adjunctive negative pressure wound therapy improves re-epithelialization rates in children with burns, yet adoption in acute burn care is inconsistent. This investigation aimed to determine barriers to the implementation of adjunctive negative pressure wound therapy for the acute management of pediatric burns and co-design targeted implementation strategies. METHODS: A sequential mixed methods design was used explore barriers to adjunctive negative pressure wound therapy implementation in acute pediatric burn care. An online questionnaire was disseminated to healthcare professionals within four major Australian pediatric hospitals, each with a dedicated burns service. Barriers were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with senior clinicians tailored implementation strategies to local contexts. A stakeholder consensus meeting consolidated implementation strategies and local processes. RESULTS: Sixty-three healthcare professionals participated in the questionnaire, and semi-structured interviews involved nine senior burn clinicians. We identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies, intervention complexity, and poor implementation planning. CONCLUSION: Multiple contextual factors affect negative pressure wound therapy uptake in acute pediatric burn settings. Results will inform a multi-state stepped-wedge cluster randomized controlled trial. Additional resources, education, training, updated policies, and guidelines are required for successful implementation. It is anticipated that adjunctive negative pressure wound therapy, in conjunction with tailored implementation strategies, will enhance adoption and sustainability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.

Intention to use physical restraint in paediatric intensive care units and correlated variables: A multicentre and cross-sectional study.

OBJECTIVES: To determine the intention to use physical restraint (PR) and the relationship with sociodemographic and professional variables of the Paediatric Intensive Care Unit (PICU) nurses. RESEARCH METHODOLOGY/DESIGN AND SETTING: A multicentre and correlational study was carried out from October 2021 to December 2023 in five paediatric intensive care units from five maternal and child hospitals in Spain. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire was provided. Moreover, sociodemographic and employment variables were registered. RESULTS: A total of 230 paediatric nurses participated in the study. A total of 87.7 % were females with an average age of 35.5 ± 9.7 years and working experience of 10.5 ± 8.4 years. The mean scores obtained were 21.1 ± 3.8 for attitude, 13.1 ± 5.0 for subjective norms, 14.4 ± 4.3 for perceived behavioural control and 28.0 ± 6.0 for intention. The nurses apply more physical restraint to anxious patients, with scarce analgesics and sedation, those affected with pharmacological withdrawal symptoms and those with a high risk of accidental removal of vital support devices or fall from bed. The sex (p = 0.007) and type of employment contract (p = 0.01) are the variables that are significantly correlated with the intention to use of PR. CONCLUSION: The paediatric nurses analysed had a moderate attitude, social pressure and perceived behavioural control towards the use of PR. IMPLICATIONS FOR CLINICAL PRACTICE: It is important to know the factors that influence the intention to use physical restraint in order to standardise safe practice for critically ill paediatric and to ensure that patients' rights are respected by obtaining informed consent and assessing the prescription, continuation and removal of physical restraint.

How Does the Proportion of Never Treatment Influence the Success of Mass Drug Administration Programs for the Elimination of Lymphatic Filariasis?

BACKGROUND: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. METHODS: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. RESULTS: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. CONCLUSIONS: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.

Expectations of preventative benefits and risk behaviors in a randomized trial evaluating oral HIV preexposure prophylaxis candidates.

When participants enrolled in an HIV prevention trial hold a preventive misconception (PM) - expectations that experimental interventions will confer protection from HIV infection - they may engage in behaviors that increase their risk of acquiring HIV. This can raise ethical concerns about whether those enrolled in the trial understand the nature of participation and their safety. Consequently, we systematically evaluated the prevalence of PM and its association with risk behaviors in a trial examining three candidate regimens for oral HIV pre-exposure prophylaxis in which all participants received at least one antiretroviral agent. Overall, trial participants exhibited relatively high preventive expectations that may be associated with an increase in risk behaviors among men who have sex with men. In addition, we identified substantial site variability in PM that necessitates future research to uncover its source. This will allow appropriate measures to be taken to mitigate PM and help ensure that participants have an accurate understanding of the potential risks and benefits of trial participation throughout the course of a trial.

Ultrasound measurement of traumatic scar and skin thickness: a scoping review of evidence across the translational pipeline of research-to-practice.

OBJECTIVES: To identify the ultrasound methods used in the literature to measure traumatic scar thickness, and map gaps in the translation of these methods using evidence across the research-to-practice pipeline. DESIGN: Scoping review. DATA SOURCES: Electronic database searches of Ovid MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature and Web of Science. Grey literature searches were conducted in Google. Searches were conducted from inception (date last searched 27 May 2022). DATA EXTRACTION: Records using brightness mode (B-mode) ultrasound to measure scar and skin thickness across the research-to-practice pipeline of evidence were included. Data were extracted from included records pertaining to: methods used; reliability and measurement error; clinical, health service, implementation and feasibility outcomes; factors influencing measurement methods; strengths and limitations; and use of measurement guidelines and/or frameworks. RESULTS: Of the 9309 records identified, 118 were analysed (n=82 articles, n=36 abstracts) encompassing 5213 participants. Reporting of methods used was poor. B-mode, including high-frequency (ie, >20 MHz) ultrasound was the most common type of ultrasound used (n=72 records; 61% of records), and measurement of the combined epidermal and dermal thickness (n=28; 24%) was more commonly measured than the epidermis or dermis alone (n=7, 6%). Reliability of ultrasound measurement was poorly reported (n=14; 12%). The scar characteristics most commonly reported to be measured were epidermal oedema, dermal fibrosis and hair follicle density. Most records analysed (n=115; 97%) pertained to the early stages of the research-to-practice pipeline, as part of research initiatives. CONCLUSIONS: The lack of evaluation of measurement initiatives in routine clinical practice was identified as an evidence gap. Diverse methods used in the literature identified the need for greater standardisation of ultrasound thickness measurements. Findings have been used to develop nine methodological considerations for practitioners to guide methods and reporting.

Improving the Cost-efficiency of Preventive Chemotherapy: Impact of New Diagnostics on Stopping Decisions for Control of Schistosomiasis.

BACKGROUND: Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. METHODS: Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. RESULTS: We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). CONCLUSIONS: We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.

How Does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma mansoni Elimination as a Public Health Problem by 2030?

BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.

Recommendations for reporting equivalent black carbon (eBC) mass concentrations based on long-term pan-European in-situ observations.

A reliable determination of equivalent black carbon (eBC) mass concentrations derived from filter absorption photometers (FAPs) measurements depends on the appropriate quantification of the mass absorption cross-section (MAC) for converting the absorption coefficient (babs) to eBC. This study investigates the spatial-temporal variability of the MAC obtained from simultaneous elemental carbon (EC) and babs measurements performed at 22 sites. We compared different methodologies for retrieving eBC integrating different options for calculating MAC including: locally derived, median value calculated from 22 sites, and site-specific rolling MAC. The eBC concentrations that underwent correction using these methods were identified as LeBC (local MAC), MeBC (median MAC), and ReBC (Rolling MAC) respectively. Pronounced differences (up to more than 50 %) were observed between eBC as directly provided by FAPs (NeBC; Nominal instrumental MAC) and ReBC due to the differences observed between the experimental and nominal MAC values. The median MAC was 7.8 ± 3.4 m2 g-1 from 12 aethalometers at 880 nm, and 10.6 ± 4.7 m2 g-1 from 10 MAAPs at 637 nm. The experimental MAC showed significant site and seasonal dependencies, with heterogeneous patterns between summer and winter in different regions. In addition, long-term trend analysis revealed statistically significant (s.s.) decreasing trends in EC. Interestingly, we showed that the corresponding corrected eBC trends are not independent of the way eBC is calculated due to the variability of MAC. NeBC and EC decreasing trends were consistent at sites with no significant trend in experimental MAC. Conversely, where MAC showed s.s. trend, the NeBC and EC trends were not consistent while ReBC concentration followed the same pattern as EC. These results underscore the importance of accounting for MAC variations when deriving eBC measurements from FAPs and emphasize the necessity of incorporating EC observations to constrain the uncertainty associated with eBC.

Adaptation and validation of the Physical Restraint-Theory of Planned Behaviour Questionnaire to the paediatric context.

OBJECTIVE: To create and test psychometrically a paediatric version of the Physical Restraint-Theory of Planned Behaviour Questionnaire to assess paediatric critical care nurses' intention to use physical restraint. DESIGN: A psychometric study. SETTING: Five medical-surgical Paeditric Intensive care Units from five hospitals in Spain. METHODS: The study took place in three phases. In phase 1, the questionnaire was adapted. In phase 2, the content validity of each item was determined, and a pilot test was conducted. In phase 3, we administered the questionnaire and determined its psychometric properties. RESULTS: The assessment of the intention to use physical restraint was extended to all critical paediatric patients, two items were eliminated from the initial questionnaire, four new items were included, and the clinical scenarios of the intention subscale were expanded from three to six. Overall content validity index for the full instrument of 0.96 out of 1. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire is made up of four subscales (attitude, subjective norms (SN), perceived behavioural control (PBC), and intention) subdivided into 7 factors and 51 items. The internal consistency for the attitude subscale obtained a Cronbach's Alpha of 0.80 to 0.73, for the SN it was 0.72 to 0.89, for the PBC it was from 0.80 to 0.73 and for the intention subscale it was 0.75. CONCLUSIONS: The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire is an instrument composed of seven factors and 51 items that validly and reliably assesses the intention of paediatric nurses to apply PR in PICUs. RELEVANCE FOR CLINICAL PRACTICE: Having this instrument will help health centres move towards restraint-free care by allowing managers to assess professionals' attitudes, beliefs, and intentions around the use of PR in PICUs.

Inter-annual trends of ultrafine particles in urban Europe.

Ultrafine particles (UFP, those with diameters ≤ 100 nm), have been reported to potentially penetrate deeply into the respiratory system, translocate through the alveoli, and affect various organs, potentially correlating with increased mortality. The aim of this study is to assess long-term trends (5-11 years) in mostly urban UFP concentrations based on measurements of particle number size distributions (PNSD). Additionally, concentrations of other pollutants and meteorological variables were evaluated to support the interpretations. PNSD datasets from 12 urban background (UB), 5 traffic (TR), 3 suburban background (SUB) and 1 regional background (RB) sites in 15 European cities and 1 in the USA were evaluated. The non-parametric Theil-Sen's method was used to detect monotonic trends. Meta-analyses were carried out to assess the overall trends and those for different environments. The results showed significant decreases in NO, NO2, BC, CO, and particle concentrations in the Aitken (25-100 nm) and the Accumulation (100-800 nm) modes, suggesting a positive impact of the implementation of EURO 5/V and 6/VI vehicle standards on European air quality. The growing use of Diesel Particle Filters (DPFs) might also have clearly reduced exhaust emissions of BC, PM, and the Aitken and Accumulation mode particles. However, as reported by prior studies, there remains an issue of poor control of Nucleation mode particles (smaller than 25 nm), which are not fully reduced with current DPFs, without emission controls for semi-volatile organic compounds, and might have different origins than road traffic. Thus, contrasting trends for Nucleation mode particles were obtained across the cities studied. This mode also affected the UFP and total PNC trends because of the high proportion of Nucleation mode particles in both concentration ranges. It was also found that the urban temperature increasing trends might have also influenced those of PNC, Nucleation and Aitken modes.

Unremitting pro-inflammatory T-cell phenotypes, and macrophage activity, following paediatric burn injury.

Objectives: The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post-burn. Methods: Flow cytometry was used to measure 25 cell markers, chemokines and cytokines which reflected both pro-inflammatory and anti-inflammatory immune profiles. Peripheral blood mononuclear cells from 6 paediatric burn patients who had returned for repeated burn and scar treatments for > 4 timepoints within 12 months post-burn were compared to four age-matched healthy controls. Results: While overall proportions of T cells, NK cells and macrophages remained relatively constant, over time percentages of these immune cells differentiated into effector and proinflammatory cell phenotypes including Th17 and activated γδ T cells. Circulating proportions of γδ T cells increased their expression of pro-inflammatory mediators throughout the burn recovery, with a 3-6 fold increase of IL-17 at 1-3 weeks, and NFκß 9-18 months post-burn. T-regulatory cell plasticity was also observed, and Treg phenotype proportions changed from systemically reduced skin-homing T-regs (CCR4+) and increased inflammatory (CCR6+) at 1-month post-burn, to double-positive cell types (CCR4+CCR6+) elevated in circulation for 18 months post-burn. Furthermore, Tregs were observed to proportionally express less IL-10 but increased TNF-α over 18 months. Conclusion: Overall, these results indicate the circulating percentages of immune cells do not increase or decrease over time post-burn, instead they become highly specialised, inflammatory and skin-homing. In this patient population, these changes persisted for at least 18 months post-burn, this 'immune distraction' may limit the ability of immune cells to prioritise other threats post-burn, such as respiratory infections.