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Abstract Atmospheric new particle formation (NPF) is a naturally occurring phenomenon, during which high concentrations of sub-10 nm particles are created through gas to particle conversion. The NPF is observed in multiple environments around the world. Although it has observable influence onto annual total and ultrafine particle number concentrations (PNC and UFP, respectively), only limited epidemiological studies have investigated whether these particles are associated with adverse health effects. One plausible reason for this limitation may be related to the absence of NPF identifiers available in UFP and PNC data sets. Until recently, the regional NPF events were usually identified manually from particle number size distribution contour plots. Identification of NPF across multi-annual and multiple station data sets remained a tedious task. In this work, we introduce a regional NPF identifier, created using an automated, machine learning based algorithm. The regional NPF event tag was created for 65 measurement sites globally, covering the period from 1996 to 2023. The discussed data set can be used in future studies related to regional NPF.

The relationship between the inverse Langevin function and the proposed r0-r1-Lambert W function is defined. The derived relationship leads to new approximations for the inverse Langevin function with lower relative error bounds than comparable published approximations. High accuracy approximations, based on Schröder’s root approximations of the first kind, are detailed. Several applications are detailed.

Currently, methodologies for the identification and apportionment of air pollution sources are not widely applied due to their high cost. We present a new approach, combining mobile measurements from multiple sensors collected from the daily walks of citizen scientists, in a high population density area of Birmingham, UK. The methodology successfully pinpoints the different sources affecting the local air quality in the area using only a handful of measurements. It was found that regional sources of pollution were mostly responsible for the PM2.5 and PM1 concentrations. In contrast, PM10 was mostly associated with local sources. The total particle number and the lung deposited surface area of PM were almost solely associated with traffic, while black carbon was associated with both the sources from the urban background and local traffic. Our analysis showed that while the effect of the hyperlocal sources, such as emissions from construction works or traffic, do not exceed the distance of a couple of hundred meters, they can influence the health of thousands of people in densely populated areas. Thus, using this novel approach we illustrate the limitations of the present measurement network paradigm and offer an alternative and versatile approach to understanding the hyperlocal factors that affect urban air quality. Mobile monitoring by citizen scientists is shown to have huge potential to enhance spatiotemporal resolution of air quality data without the need of extensive and expensive campaigns.

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. HIGHLIGHTS One dimensional steady flow analysis is performed in this study.; Velocity plots were generated to get clear idea about velocity of each station.; Terrain plots were generated from HEC-RAS.; Critical flood prone area identification can be done by analysing velocity plots.; HEC-RAS modelling is effective for flow studies.;

Abstract Traditional statistical methods (TSM) and machine learning (ML) methods have been widely used to separate the effects of emissions and meteorology on air pollutant concentrations, while their performance compared to the chemistry transport model has been less fully investigated. Using the Community Multiscale Air Quality Model (CMAQ) as a reference, a series of experiments was conducted to comprehensively investigate the performance of TSM (e.g., multiple linear regression and Kolmogorov–Zurbenko filter) and ML (e.g., random forest and extreme gradient boosting) approaches in quantifying the effects of emissions and meteorology on the trends of fine particulate matter (PM2.5) during 2013−2017. Model performance evaluation metrics suggested that the TSM and ML methods can explain the variations of PM2.5 with the highest performance from ML. The trends of PM2.5 showed insignificant differences (p > 0.05) for both the emission-related ( $${{\rm{PM}}}_{2.5}^{{\rm{EMI}}}$$ PM 2.5 EMI ) and meteorology-related components between TSM, ML, and CMAQ modeling results. $${{\rm{PM}}}_{2.5}^{{\rm{EMI}}}$$ PM 2.5 EMI estimated from ML showed the least difference to that from CMAQ. Considering the medium computing resources and low model biases, the ML method is recommended for weather normalization of PM2.5. Sensitivity analysis further suggested that the ML model with optimized hyperparameters and the exclusion of temporal variables in weather normalization can further produce reasonable results in emission-related trends of PM2.5.

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.

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.

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.

Abstract Very high concentrations of ultrafine particles (UFP) were measured at Heathrow Airport London. Exposure to UFP is strongly linked to adverse health effects and guidance for exposure limits has recently been provided by the World Health Organization (WHO). Using 1 s resolution UFP measurements and aircraft GPS data, measurements were assigned to individual aircraft and their operating mode, and this information was used to model UFP emission rates. In all cases, the highest emission rates were associated with departing aircraft, with rates for larger aircraft higher than smaller aircraft. Emission rates per passenger is influenced by the number of passengers carried, especially for arriving aircraft. Calculated emission rates are significantly higher than stated literature values, due to the inclusion of condensable particles in the measurements. These condensable particles are specifically not included in the regulated emission rates. Measured UFP concentrations within the airport boundary (and therefore not accessible to the general public) exceed the WHO guidance, indicating that UFP concentrations outside of the airport boundary could also be of concern. Assessing population exposure close to airports will be of increasing importance in future.

Abstract Successful air quality management and control not only requires measurements of air pollution levels. It also requires information on the sources of air pollution, and their relative magnitudes and importance, to plan and enact cost-effective control measures. This paper provides an important breakthrough towards the wider and more comprehensive use of source apportionment via low-cost techniques. Low-cost sensor measurements, along with the statistical methods of Positive Matrix Factorization (PMF) and k-means clustering, were able to successfully pinpoint and quantify the main sources of pollution in three regulatory important sites (a construction site, a quarry and a roadside). The anticipated levels of pollution, which were dependent on meteorological conditions and temporal variations, were assessed. The analysis provides information crucial for successful air quality management and control at a significantly lower cost than previously achieved. The strengths and weaknesses of the methodologies used are illustrated and discussed.

Abstract Background Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes. Methods During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections. Results The predominant STH species was the hookworm Necator americanus (overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection with N. americanus among children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection with N. americanus were also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93, P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57, P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70, P

Background Paediatric donor site wounds are often complicated by dyspigmentation following a split-thickness skin graft. These easily identifiable scars can potentially never return to normal pigmentation. A Regenerative Epidermal Suspension (RES) has been shown to improve pigmentation in patients with vitiligo, and in adult patients following a burn injury. Very little is known regarding the efficacy of RES for the management of donor site scars in children.Methods and analysis A pilot randomised controlled trial of 40 children allocated to two groups (RES or no RES) standard dressing applied to donor site wounds will be conducted. All children aged 16 years or younger requiring a split thickness skin graft will be screened for eligibility. The primary outcome is donor site scar pigmentation 12 months after skin grafting. Secondary outcomes include re-epithelialisation time, pain, itch, dressing application ease, treatment satisfaction, scar thickness and health-related quality of life. Commencing 7 days after the skin graft, the dressing will be changed every 3–5 days until the donor site is ≥ 95% re-epithelialised. Data will be collected at each dressing change and 3, 6 and 12 months post skin graft.Ethics and dissemination Ethics approval was confirmed on 11 February 2019 by the study site Human Research Ethics Committee (HREC) (HREC/18/QCHQ/45807). Study findings will be published in peer-reviewed journals and presented at national and international conferences. This study was prospectively registered on the Australian New Zealand Clinical Trials Registry (available at https://anzctr.org.au/ACTRN12620000227998.aspx).Trial registration number Australian New Zealand Clinical Trials Registry [Available at https://anzctr.org.au/ACTRN12620000227998.aspx]

Abstract 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 NFκβ 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.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKƴ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.

Due to the implementation of air pollution control measures in China, air quality has significantly improved, although there are still additional issues to be addressed. This study used the long-term trends of air pollutants to discuss the achievements and challenges in further improving air quality in China. The Kolmogorov-Zurbenko (KZ) filter and multiple-linear regression (MLR) were used to quantify the meteorology-related and emission-related trends of air pollutants from 2014 to 2022 in China. The KZ filter analysis showed that PM2.5 decreased by 7.36 ± 2.92% yr−1, while daily maximum 8-h ozone (MDA8 O3) showed an increasing trend with 3.71 ± 2.89% yr−1 in China. The decrease in PM2.5 and increase in MDA8 O3 were primarily attributed to changes in emission, with the relative contribution of 85.8% and 86.0%, respectively. Meteorology variations, including increased ambient temperature, boundary layer height, and reduced relative humidity, also contributed to the reduction of PM2.5 and the enhancement of MDA8 O3. The emission-related trends of PM2.5 and MDA8 O3 exhibited continuous decrease and increase, respectively, from 2014 to 2022, while the variation rates slowed during 2018–2020 compared to that during 2014–2017, highlighting the challenges in further improving air quality, particularly in simultaneously reducing PM2.5 and O3. This study recommends reducing NH3 emissions from the agriculture sector in rural areas and transport emissions in urban areas to further decrease PM2.5 levels. Addressing O3 pollution requires the reduction of O3 precursor gases based on site-specific atmospheric chemistry considerations.

Objectives:. Eccrine angiomatous hamartoma (EAH) is a rare vascular anomaly with mixed eccrine and vascular components, typically identified in children. While benign, EAH can cause significant morbidity and be difficult to treat. The aims of this case series were to identify all patients with EAH that have been seen at the Queensland Children’s Hospital and describe their phenotypic and somatic genotypic details, in an effort to contribute to the limiting understanding and literature surrounding this condition. Methods:. Individuals with EAH were retrospectively identified through engagement in a multidisciplinary vascular anomaly clinic in a tertiary Australian children’s hospital. All individuals had a previous histological diagnosis of EAH. High-read-depth sequencing of a panel of 27 genes known to be associated with vascular anomalies was undertaken on affected tissue. Samples were rereviewed by a senior pathologist and geneticist for this study. Results:. Five cases of EAH were identified. All were associated with 1 of 3 somatic PIK3CA variants (c.1633G>A;p.Glu545Lys, c.1624G>A;p.Glu542Lys, and c.3140A>G;p.Histo1047Arg) in low allele fractions. These variants have previously been reported in a range of tumors and vascular anomalies, including PIK3CA-related overgrowth spectrum, but not in EAH. Conclusion:. Occurrence of somatic PIK3CA variants in EAH provides evidence for a novel gene-disease association and is plausibly the cause of EAH in some individuals. This finding expands the phenotypic spectrum of PIK3CA, contributes to understanding of the pathophysiology of this rare condition, and may avail molecularly targeted therapy in the future.

Summary: Background: Soil-transmitted helminth (STH) infection control programs typically consist of school-based preventive chemotherapy (PC) targeted to school-aged children. STH reservoirs in untreated community members contribute to ongoing transmission in children. The CoDe-STH (Community Deworming against STH) trial, conducted in Dak Lak province, Vietnam, between October 2019 and November 2020, aimed to determine whether community-wide mass drug administration (MDA) is more effective than school-based targeted PC in reducing STH prevalence and intensity in children. Methods: In this two-arm cluster randomised controlled trial, 64 primary schools were randomly assigned 1:1 to receive either school-based targeted PC (“school arm”) or community-wide MDA (“community arm”). A single dose of albendazole 400 mg was used for deworming. The primary outcome was hookworm prevalence in schoolchildren, measured using quantitative real-time PCR. We also measured infection intensity for Necator americanus only, using qPCR cycle threshold (Ct) values converted into eggs per gram of faeces (EPG). Analysis was by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000309189). Findings: The analysis included 4955 children in the school arm and 5093 children in the community arm. N. americanus was the dominant STH species. The relative reduction in hookworm prevalence was not significantly different between the school arm (30.1%, 95% confidence interval [CI] 20.5–36.9) and the community arm (34.6%, 95% CI 19.9–49.4). Due to lower baseline prevalence than expected, the study was underpowered to detect a difference in prevalence reduction between the study arms. The community arm showed significantly greater relative reduction in N. americanus infection intensity (56.0%, 95% CI 39.9–72.1) compared to the school arm (3.4%, 95% CI −24.7 to 31.4). The community arm also showed greater relative reduction in prevalence of moderate-to-heavy intensity (≥2000 EPG) N. americanus infections (81.1%; 95% CI 69.7–92.6) compared to the school arm (39.0%, 95% CI 13.7–64.2). Interpretation: Although no impact was seen on overall prevalence, community-wide MDA was more effective in lowering N. americanus infection intensity in schoolchildren compared to school-based targeted PC, measured 12 months after one round of albendazole deworming with high coverage. Funding: National Health and Medical Research Council, Australia (APP1139561).

Based on the geometry of a radial function, a sequence of approximations for arcsine, arccosine and arctangent are detailed. The approximations for arcsine and arccosine are sharp at the points zero and one. Convergence of the approximations is proved and the convergence is significantly better than Taylor series approximations for arguments approaching one. The established approximations can be utilized as the basis for Newton-Raphson iteration and analytical approximations, of modest complexity, and with relative error bounds of the order of 10−16, and lower, can be defined. Applications of the approximations include: first, upper and lower bounded functions, of arbitrary accuracy, for arcsine, arccosine and arctangent. Second, approximations with significantly higher accuracy based on the upper or lower bounded approximations. Third, approximations for the square of arcsine with better convergence than well established series for this function. Fourth, approximations to arccosine and arcsine, to even order powers, with relative errors that are significantly lower than published approximations. Fifth, approximations for the inverse tangent integral function and several unknown integrals.

Intro: Treating complex paediatric wounds is a challenge for many clinicians. Biodegradable Temporising Matrix (BTM) is a completely synthetic product that has shown promise in adults with acute burns, complex wounds, and reconstructive procedures. Currently, there is little documentation regarding the use of BTM in the paediatric population. Method: A retrospective chart review was conducted of all children who required application of BTM for wound treatment. Children were grouped into categories according to the type of injury or condition including thermal, friction, and electrical injuries, scar reconstruction, and various wound defects. Outcomes of interest included infection rates, time to application of BTM and split-thickness skin graft (SSG), dressings used, and overall functional and cosmetic outcomes. Results: 63 children were identified. Thermal (19/63) and friction (10/63) injuries represented the largest groups. Males accounted for 68 % of total children with lower limbs and feet most often affected. The median time for application of BTM was 7.5 days and 27 days from time of application of BTM to SSG. BTM provided satisfactory options for early wound closure and the ability to convert complex wounds, however it still does not negate the need for scar management. Conclusion: From our review, BTM is a versatile product that has shown positive results for the treatment of complex wounds in the paediatric population. It represents the largest consecutive BTM case series in either adult or paediatric populations to date.

Ultrafine particles (UFPs) are respirable particles with a diameter less than 100 nm, which some studies have associated with adverse effects upon health. UFPs are currently not regulated as the health evidence is insufficient and very few observational data are available in most cities. The 2021 WHO Global Air Quality Guidelines highlighted the pressing issue of UFPs and provided a good practice statement for UFPs, which recommends that more measurement and modelling studies are implemented in future. Particle number concentrations (PNC) are the most common metric for UFPs as this fraction normally dominates the total ambient PNC in urban environments. This study simulates the dispersion of particle number concentrations in the West Midlands (a metropolitan area), UK using the local scale ADMS-Urban model, which is an advanced quasi-Gaussian plume dispersion modelling system. ADMS-Urban implements a physics-based approach to represent the characteristics of the atmospheric boundary layer and has been widely used in the dispersion modelling of air pollutants. It can represent a variety of source types (such as road and grid emissions) occurring in urban environments and requires a range of input data. Particle number was used as a passive scalar, with no inclusion of aerosol microphysics within the model, as a first implementation in the ADMS-Urban model for the West Midlands, UK. Evaluation was conducted by comparing the modelled (from a receptor run) and measured data at the Birmingham Air Quality Supersite. Overall, the model performed well although there was a slight underestimation for PNC. Based on the modelling output from a contour run, PNC maps at a variety of spatial scales (i.e. street scale, ward level and local authority level) and temporal resolutions (i.e. annual, 24-hour, and 1-hour) were generated. PNC mapping could be linked to local population and health data for potential epidemiological studies.

Abstract Background In February 2021, over one hundred scientists and policy experts participated in a web-based Workshop to discuss the ways that divergent evaluations of evidence and scientific uncertainties are used to delay timely protection of human health and the environment from exposures to hazardous agents. The Workshop arose from a previous workshop organized by the European Environment Agency (EEA) in 2008 and which also drew on case studies from the EEA reports on ‘Late Lessons from Early Warnings’ (2001, 2013). These reports documented dozens of hazardous agents including many chemicals, for which risk reduction measures were delayed for decades after scientists and others had issued early and later warnings about the harm likely to be caused by those agents. Results Workshop participants used recent case studies including Perfluorooctanoic acid (PFOA), Extremely Low Frequency – Electrical Magnetic Fields (ELF-EMF fields), glyphosate, and Bisphenol A (BPA) to explore myriad reasons for divergent outcomes of evaluations, which has led to delayed and inadequate protection of the public’s health. Strategies to overcome these barriers must, therefore, at a minimum include approaches that 1) Make better use of existing data and information, 2) Ensure timeliness, 3) Increase transparency, consistency and minimize bias in evidence evaluations, and 4) Minimize the influence of financial conflicts of interest. Conclusion The recommendations should enhance the production of “actionable evidence,” that is, reliable evaluations of the scientific evidence to support timely actions to protect health and environments from exposures to hazardous agents. The recommendations are applicable to policy and regulatory settings at the local, state, federal and international levels.

Abstract Atmospheric particulate matter (PM) has a significant impact on both the natural environment and human health. Iron is one of the most abundant elements in the earth’s crust, playing an important role in geochemical processes, and is also an important trace component in atmospheric PM. In recent years, with the rapid development of non-traditional (metal) stable isotope technologies, new solutions and methods for the source apportionments of heavy metal elements have been put forward. Stable iron isotope analysis has become an effective tool to trace iron in atmospheric particles. This review paper briefly summarizes the recent progress of atmospheric iron isotope geochemistry. We show that some of the major natural and anthropogenic PM sources have different iron isotopic compositions. A Bayesian isotopic mixing model MixSIAR was used to quantitatively re-evaluate the contributions of different sources to iron in both urban and marine aerosols based on iron isotopic data in the literature. The results highlight the value of stable iron isotope analyses as an effective tool in the source apportionment of atmospheric aerosols.

Abstract In order to predict the impacts of reductions in air pollutant emissions, it is important to know whether secondary pollutant concentrations will decline in direct proportion to the reduction in their precursor, referred to as linearity. Trends in airborne concentrations of nitrate, sulfate, and SOC at sites in southern England are compared with emissions and concentration trends for sulfur dioxide (SO2), oxides of nitrogen (NO x ), and non-methane VOC, and show some increased ratios of concentrations to emissions, strongly suggestive of non-linearity in the primary-secondary pollutant relationships for nitrate, but not the other pollutants. Analysis of a further 20-year dataset from the AGANET network shows a decline of nitrate concentrations significantly lower than that of NO x emissions and ambient NO x concentrations. For sulfate, the decline lies between that of emissions and airborne concentrations of SO2. Back trajectory analysis and Potential Source Contribution Function mapping for 2014–2018 show that the highest concentrations of secondary constituents in southern England are associated with air masses originating in mainland Europe, with 42% of sulfate, 55% of nitrate, and 35% of SOC estimated to be associated with air masses entering the UK from the European mainland.

This study analyzed the variability of equivalent black carbon (eBC) mass concentrations and their sources in urban Europe to provide insights into the use of eBC as an advanced air quality (AQ) parameter for AQ standards. This study compiled eBC mass concentration datasets covering the period between 2006 and 2022 from 50 measurement stations, including 23 urban background (UB), 18 traffic (TR), 7 suburban (SUB), and 2 regional background (RB) sites. The results highlighted the need for the harmonization of eBC measurements to allow for direct comparisons between eBC mass concentrations measured across urban Europe. The eBC mass concentrations exhibited a decreasing trend as follows: TR > UB > SUB > RB. Furthermore, a clear decreasing trend in eBC concentrations was observed in the UB sites moving from Southern to Northern Europe. The eBC mass concentrations exhibited significant spatiotemporal heterogeneity, including marked differences in eBC mass concentration and variable contributions of pollution sources to bulk eBC between different cities. Seasonal patterns in eBC concentrations were also evident, with higher winter concentrations observed in a large proportion of cities, especially at UB and SUB sites. The contribution of eBC from fossil fuel combustion, mostly traffic (eBCT) was higher than that of residential and commercial sources (eBCRC) in all European sites studied. Nevertheless, eBCRC still had a substantial contribution to total eBC mass concentrations at a majority of the sites. eBC trend analysis revealed decreasing trends for eBCT over the last decade, while eBCRC remained relatively constant or even increased slightly in some cities.

There is ample evidence from occupational studies that exposure to a mixture of Polycyclic Aromatic Hydrocarbons (PAHs) is causally associated with an increased incidence of lung cancers. In both occupational atmospheres and ambient air, PAHs are present as a mixture of many compounds, but the composition of the mixture in ambient air differs from that in the occupational atmosphere, and varies in time and space in ambient air. Estimates of cancer risk for PAH mixtures are based upon unit risks which derive from extrapolation of occupational exposure data or animal model data, and in the case of the WHO use one compound, benzo[a]pyrene as a marker for the entire mixture, irrespective of composition. The U.S. EPA has used an animal exposure study to derive a unit risk for inhalation exposure to benzo[a]pyrene alone, and there have been a number of rankings of relative carcinogenic potency for other PAHs which many studies have used to calculate a cancer risk from the PAHs mixture, frequently incorrectly by adding the estimated relative risks of individual compounds, and applying the total “B[a]P equivalent” to the WHO unit risk, which already applies to the entire mixture. Such studies are often based upon data solely for the historic US EPA group of 16 compounds which do not include many of the apparently more potent carcinogens. There are no data for human cancer risk of individual PAHs, and conflicting evidence of additivity of PAH carcinogenicity in mixtures. This paper finds large divergences between risk estimates deriving from the WHO and U.S. EPA methods, as well as considerable sensitivity to the mixture composition, and assumed PAH relative potencies. Of the two methods, the WHO approach appears more likely to provide reliable risk estimates, but recently proposed mixture-based approaches using in vitro toxicity data may offer some advantages.

Abstract The Arctic environment has changed profoundly in recent decades. Aerosol particles are involved in numerous feedback mechanisms in the Arctic, e.g., aerosol-cloud/radiation interactions, which have important climatic implications. To understand changes in different Arctic aerosol types and number concentrations, we have performed a trend analysis of particle number size distributions, their properties, and their associated air mass history at Villum Research Station, northeastern Greenland, from 2010 to 2018. We found that, during spring, the total/ultrafine mode number concentration and the time air masses spent over the open ocean is significantly increasing, which can be ascribed to transport patterns changing to more frequent arrival from the ice-free Greenland Sea. We found that, during summer, the total/ultrafine mode number concentration, the occurrence of the Nucleation cluster (i.e. newly formed particles from gas to particle conversion), and the time air masses spent over the open ocean is significantly increasing. This can also be attributed to changing transport patterns, here with air masses arriving more frequently from Baffin Bay. Finally, we found that, during autumn, the ultrafine number concentration and the occurrence of the Pristine cluster (i.e. clean, natural Arctic background conditions) is significantly increasing, which is likely due to increasing amounts of accumulated precipitation along the trajectory path and decreasing time air masses spent above the mixed layer, respectively. Our results demonstrate that changing circulation and precipitation patterns are the factors predominantly affecting the trends in aerosol particle number concentrations and the occurrence of different aerosol types in northeastern Greenland.

Introduction Negative pressure wound therapy (NPWT) in acute burn care may decrease the time to re-epithelialisation by more than 20%. Despite this, the perceived burden of use; including therapeutic, physical and financial, have limited the use of NPWT in acute burn care. This might be minimised by using the small, ultraportable, single-use NPWT device PICO as opposed to larger devices, which to date has never been studied in acute burn care. This research will; therefore, primarily assess the feasibility, acceptability and safety of PICO in paediatric burns. Secondary outcomes include time to re-epithelialisation, pain, itch, cost and scar formation.Methods and analysis This protocol details a clinical trial methodology and is pre-results. This single site, prospective, pilot randomised controlled trial will be conducted in an Australian quaternary paediatric burns centre. Participants must be aged ≤16 years, otherwise well and managed within 24 hours of sustaining a burn that fits beneath a PICO dressing. Thirty participants will be randomised to one of three groups: group A: Mepitel and ACTICOAT, group B: Mepitel, ACTICOAT and PICO and group C: Mepitel, ACTICOAT Flex and PICO. Patient outcomes will be recorded at each dressing change to assess efficacy and safety outcomes until 3 months postburn wound re-epithelialisation. Surveys, randomisation and data storage will be undertaken via online platforms and physical data storage collated at the Centre for Children’s Health Research, Brisbane, Australia. Analysis will be done by using StataSE 17.0 statistical software.Ethics and dissemination Ethics has been obtained from Queensland Health and Griffith Human Research Ethics committees including a site-specific approval. These data will be disseminated via clinical meetings, conference presentations and peer-reviewed journals.Trial registration number ACTRN12622000009718.

Air quality is one of the most important factors in public health. While outdoor air quality is widely studied, the indoor environment has been less scrutinised, even though time spent indoors is typically much greater than outdoors. The emergence of low-cost sensors can help assess indoor air quality. This study provides a new methodology, utilizing low-cost sensors and source apportionment techniques, to understand the relative importance of indoor and outdoor air pollution sources upon indoor air quality. The methodology is tested with three sensors placed in different rooms inside an exemplar house (bedroom, kitchen and office) and one outdoors. When the family was present, the bedroom had the highest average concentrations for PM2.5 and PM10 (3.9 ± 6.8 ug/m3 and 9.6 ± 12.7 μg/m3 respectively), due to the activities undertaken there and the presence of softer furniture and carpeting. The kitchen, while presenting the lowest PM concentrations for both size ranges (2.8 ± 5.9 ug/m3 and 4.2 ± 6.9 μg/m3 respectively), presented the highest PM spikes, especially during cooking times. Increased ventilation in the office resulted in the highest PM1 concentration (1.6 ± 1.9 μg/m3), highlighting the strong effect of infiltration of outdoor air for the smallest particles. Source apportionment, via positive matrix factorisation (PMF), showed that up to 95 % of the PM1 was found to be of outdoor sources in all the rooms. This effect was reduced as particle size increased, with outdoor sources contributing >65 % of the PM2.5, and up to 50 % of the PM10, depending on the room studied. The new approach to elucidate the contributions of different sources to total indoor air pollution exposure, described in this paper, is easily scalable and translatable to different indoor locations.

Diesel engines are a major contributor to emissions of both Black Carbon (BC) and ultrafine particles. Analysis of data from the only roadside monitoring site in Europe with a continuous dataset for size-segregated particle number count (Marylebone Road, London) from 2010 to 2021 reveals that the growing number of vehicles fitted with a Diesel Oxidation Catalyst (DOC) and Diesel Particle Filter (DPF) has been very effective in controlling the emissions of solid particles and hence BC, but that there has been little change in the liquid mode (104 cm−3 /24-hour mean) defined by WHO. BC declined by 81% between 2014 and 2021, but the ultrafine particle (

Objective. To estimate the point prevalence and likely ranges of pregnancy-induced hypertension, preeclampsia, gestational diabetes, low birth weight and preterm delivery in Latin America and the Caribbean, and evaluate the heterogeneity of the estimates. Methods. We conducted a systematic review and meta-analysis of observational studies reporting the prevalence of maternal and perinatal adverse outcomes in populations in Latin American and the Caribbean published between 2000 and 2019 in English, Spanish, or Portuguese. We searched PubMed, Embase, and LILACS. We estimated the point prevalence and evaluated overall heterogeneity and, in sub-group analyses, heterogeneity by study design and level of bias. Results. Of 1087 records retrieved, 50 articles were included in the review: two on hypertensive disorders of pregnancy, 14 on pre-eclampsia, six on gestational diabetes, nine on low birth weight and 19 on preterm birth. No meta-analysis for hypertensive disorders of pregnancy could be done because of the small number of studies. Point prevalence estimates and 95% confidence intervals (CIs) for pre-eclampsia, gestational diabetes, low birth weight, and preterm birth were: 6.6% (95% CI: 4.9%, 8.6%), 8.5% (95% CI: 3.9%, 14.7%), 8.5% (95% CI: 7.2%, 9.8%), and 10.0% (95% CI: 8.0%, 12.0%), respectively. We observed substantial heterogeneity overall and by study design. No major differences in estimates were observed by level of bias. Conclusions. The results of this study provide updated estimates of some of the most prevalent adverse pregnancy and perinatal outcomes in Latin America and the Caribbean. They highlight that important heterogeneity exists in prevalence estimates, which may reflect the diversity of populations in the region.

Abstract Aerosols produced from the oxidation of volatile/semi-volatile organic compounds (VOCs/SVOCs), known as secondary organic aerosol (SOA), account for a significant fraction of atmospheric airborne particles. This paper reviews the current understanding of SOA formation from gas-phase oxidation with a focus on anthropogenic precursors and their reaction products from atmospheric simulation chamber studies. The review summarises the major reaction products derived from main groups of SOA precursors (e.g., alkanes, aromatics), SOA yields and the factors controlling SOA formation. We highlight that lab-derived SOA yield depends strongly upon, not only the concentrations of SOA precursors and oxidants but also simulation conditions.

Schröder approximations of the first kind, modified for the inverse function approximation case, are utilized to establish general analytical approximation forms for an inverse function. Such general forms are used to establish arbitrarily accurate analytical approximations, with a set relative error bound, for an inverse function when an initial approximation, typically with low accuracy, is known. Approximations for arcsine, the inverse of x − sin(x), the inverse Langevin function and the Lambert W function are used to illustrate this approach. Several applications are detailed. For the root approximation of a function, Schröder approximations of the first kind, based on the inverse of a function, have an advantage over the corresponding generalization of the standard Newton–Raphson method, as explicit analytical expressions for all orders of approximation can be obtained.

Ottilie et al. employ an experimental evolution approach to investigate the role of transcription factors in yeast chemical resistance. Most emergent mutations in resistant strains were enriched in transcription factor coding genes, highlighting their importance in drug resistance.

Abstract Background In January 2021, the World Health Organization published the 2021–2030 roadmap for the control of neglected tropical diseases (NTDs). The goal for schistosomiasis is to achieve elimination as a public health problem (EPHP) and elimination of transmission (EOT) in 78 and 25 countries (by 2030), respectively. Mass drug administration (MDA) of praziquantel continues to be the main strategy for control and elimination. However, as there is limited availability of praziquantel, it is important to determine what volume of treatments are required, who should be targeted and how frequently treatment must be administered to eliminate either transmission or morbidity caused by infection in different endemic settings with varied transmission intensities. Methods and Results In this paper, we employ two individual-based stochastic models of schistosomiasis transmission developed independently by the Imperial College London (ICL) and University of Oxford (SCHISTOX) to determine the optimal treatment strategies to achieve EOT. We find that treating school-age children (SAC) only is not sufficient to achieve EOT within a feasible time frame, regardless of the transmission setting and observed age–intensity of infection profile. Both models show that community-wide treatment is necessary to interrupt transmission in all endemic settings with low, medium and high pristine transmission intensities. Conclusions The required MDA coverage level to achieve either transmission or morbidity elimination depends on the prevalence prior to the start of treatment and the burden of infection in adults. The higher the worm burden in adults, the higher the coverage levels required for this age category through community-wide treatment programmes. Therefore, it is important that intensity and prevalence data are collected in each age category, particularly from SAC and adults, so that the correct coverage level can be calculated and administered. Graphical Abstract

The 2017–2019 hourly particle number size distributions (PNSD) from 26 sites in Europe and 1 in the US were evaluated focusing on 16 urban background (UB) and 6 traffic (TR) sites in the framework of Research Infrastructures services reinforcing air quality monitoring capacities in European URBAN & industrial areaS (RI-URBANS) project. The main objective was to describe the phenomenology of urban ultrafine particles (UFP) in Europe with a significant air quality focus.The varying lower size detection limits made it difficult to compare PN concentrations (PNC), particularly PN10-25, from different cities. PNCs follow a TR > UB > Suburban (SUB) order. PNC and Black Carbon (BC) progressively increase from Northern Europe to Southern Europe and from Western to Eastern Europe. At the UB sites, typical traffic rush hour PNC peaks are evident, many also showing midday-morning PNC peaks anti-correlated with BC. These peaks result from increased PN10-25, suggesting significant PNC contributions from nucleation, fumigation and shipping.Site types to be identified by daily and seasonal PNC and BC patterns are: (i) PNC mainly driven by traffic emissions, with marked correlations with BC on different time scales; (ii) marked midday/morning PNC peaks and a seasonal anti-correlation with PNC/BC; (iii) both traffic peaks and midday peaks without marked seasonal patterns. Groups (ii) and (iii) included cities with high insolation.PNC, especially PN25-800, was positively correlated with BC, NO2, CO and PM for several sites. The variable correlation of PNSD with different urban pollutants demonstrates that these do not reflect the variability of UFP in urban environments. Specific monitoring of PNSD is needed if nanoparticles and their associated health impacts are to be assessed. Implementation of the CEN-ACTRIS recommendations for PNSD measurements would provide comparable measurements, and measurements of

Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). Here, we measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 48-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study's active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes.

Three microwave-assisted digestion procedures, followed by analysis of digestates employing inductively coupled mass spectrometry (ICP-MS) were evaluated for use in the determination of elements at trace and ultra-trace levels in PM2.5 samples. Digestion procedure 1 used 2.5 mL HNO3 (65%) at 200 °C. Procedure 2, consisted of a two-stage digestion step at 200 °C with 2.5 mL HNO3 (65%) and 3 μL HF (48%) followed by 24 μL H3BO3 (5%). A 10-fold increase in the amounts of HF and H3BO3 was used for procedure 3. The addition of HF/H3BO3 was carried out to aid the dissolution of silicate matrices and refractory compounds. The digestions were carried out using PTFE ultra-trace inserts which increased the sample throughput threefold. The addition of small quantities of HF resulted in the effective solubilisation of Na, Mg, Al, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Sr, Cd, Sb and Pb. The optimal method using HNO3/HF/H3BO3 digestion as in procedure 3 showed recovery efficiency greater than 70% for all elements. The validated method was applied to quantify the elemental content of indoor and outdoor PM2.5 (with samples

Abstract Background/objective REFLECTIONS B538–02 is a randomized, double-blind comparative study of the adalimumab (ADL) biosimilar PF-06410293, (ADL-PF), and reference ADL sourced from the European Union (ADL-EU) in patients with active RA. Therapeutic equivalence was demonstrated based on ACR20 responses at week 12 (primary endpoint). We report long-term safety, immunogenicity, and efficacy of ADL-PF in patients who continued ADL-PF treatment throughout 78 weeks or who switched from ADL-EU to ADL-PF at week 26 or week 52. Methods Eligible patients (2010 ACR/EULAR RA diagnosis criteria for ≥ 4 months; inadequate response to MTX, ≤ 2 doses non-ADL biologic), stratified by geographic regions were initially randomized (1:1) in treatment period 1 (TP1) to ADL-PF or ADL-EU (40 mg subcutaneously, biweekly), both with MTX (10–25 mg/week). At week 26 (start of TP2), patients receiving ADL-EU were re-randomized to remain on ADL-EU or transition to ADL-PF for 26 weeks. At week 52 (start of TP3), all patients received open-label treatment with ADL-PF for 26 weeks and were followed after last treatment dose to week 92. To evaluate maintenance of response after switching or remaining on ADL-PF, ACR20, DAS28-4(CRP), and other measures of clinical response/remission were assessed through week 78 as secondary endpoints. Three groups were evaluated: biosimilar, week 26 switch, and week 52 switch. Results Overall, 507 patients participated in TP3. ACR20 response rates at week 52 were 88.4%, 88.2%, and 87.6% for the biosimilar, week 26, and week 52 switch groups, respectively. ACR20 response rates and DAS28-4(CRP) scores were sustained and comparable across groups in TP3. Incidence of treatment-emergent adverse events (AEs) during TP3 and follow-up was 42.6% (biosimilar), 37.0% (week 26 switch), and 50.8% (week 52 switch); 3 (0.6%) patients (all week 52 switch) reported treatment-related serious AEs. ADL-PF was generally well tolerated, with a comparable safety profile across groups. Overall, incidences of patients with anti-drug antibodies in TP3 and follow-up were comparable among groups (46.1%, 46.5%, and 54.2%, respectively). Conclusions There were no clinically meaningful differences in safety, immunogenicity, and efficacy for patients who were maintained on ADL-PF for 78 weeks and those who had switched from ADL-EU at week 26 or week 52. Trial registration ClinicalTrials.gov , NCT02480153. First posted on June 24, 2015; EU Clinical Trials Register; EudraCT number: 2014-000352-29. Start date, October 27, 2014

Salmonella enterica serovar Typhi (S. Typhi) is either widely distributed or proximally transmitted via fecally-contaminated food or water to cause typhoid fever. In Samoa, where endemic typhoid fever has persisted over decades despite water quality and sanitation improvements, the local patterns of S. Typhi circulation remain unclear. From April 2018-June 2020, epidemiologic data and GPS coordinates were collected during household investigations of 260 acute cases of typhoid fever, and 27 asymptomatic shedders of S. Typhi were detected among household contacts. Spatial and temporal distributions of cases were examined using Average Nearest Neighbor and space-time hotspot analyses. In rural regions, infections occurred in sporadic, focal clusters contrasting with persistent, less clustered cases in the Apia Urban Area. Restrictions to population movement during nationwide lockdowns in 2019-2020 were associated with marked reductions of cases. Phylogenetic analyses of isolates with whole genome sequences (n = 186) revealed one dominant genotype 3.5.4 (n = 181/186) that contains three Samoa-exclusive sub-lineages: 3.5.4.1, 3.5.4.2, and 3.5.4.3. Variables of patient sex, age, and geographic region were examined by phylogenetic groupings, and significant differences (p

ABSTRACT For decades, the remote island nation of Samoa (population ~200,000) has faced endemic typhoid fever despite improvements in water quality, sanitation, and economic development. We recently described the epidemiology of typhoid fever in Samoa from 2008 to 2019 by person, place, and time; however, the local Salmonella enterica serovar Typhi (S. Typhi) population structure, evolutionary origins, and genomic features remained unknown. Herein, we report whole genome sequence analyses of 306 S. Typhi isolates from Samoa collected between 1983 and 2020. Phylogenetics revealed a dominant population of rare genotypes 3.5.4 and 3.5.3, together comprising 292/306 (95.4%) of Samoan versus 2/4934 (0.04%) global S. Typhi isolates. Three distinct 3.5.4 genomic sublineages were identified, and their defining polymorphisms were determined. These dominant Samoan genotypes, which likely emerged in the 1970s, share ancestry with other 3.5 clade isolates from South America, Southeast Asia, and Oceania. Additionally, a 106-kb pHCM2 phenotypically cryptic plasmid, detected in a 1992 Samoan S. Typhi isolate, was identified in 106/306 (34.6%) of Samoan isolates; this is more than double the observed proportion of pHCM2-containing isolates in the global collection. In stark contrast with global S. Typhi trends, resistance-conferring polymorphisms were detected in only 15/306 (4.9%) of Samoan S. Typhi, indicating overwhelming susceptibility to antibiotics that are no longer effective in most of South and Southeast Asia. This country-level genomic framework can help local health authorities in their ongoing typhoid surveillance and control efforts, as well as fill a critical knowledge gap in S. Typhi genomic data from Oceania. IMPORTANCE In this study, we used whole genome sequencing and comparative genomics analyses to characterize the population structure, evolutionary origins, and genomic features of S. Typhi associated with decades of endemic typhoid fever in Samoa. Our analyses of Samoan isolates from 1983 to 2020 identified a rare S. Typhi population in Samoa that likely emerged around the early 1970s and evolved into sublineages that are presently dominant. The dominance of these endemic genotypes in Samoa is not readily explained by genomic content or widespread acquisition of antimicrobial resistance. These data establish the necessary framework for future genomic surveillance of S. Typhi in Samoa for public health benefit.

Objectives: Venous thrombosis has been widely described in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, arterial thrombosis has rarely been reported. This study aims to assess the incidence, risk factors, interventions, and outcomes of acute aortoiliac arterial thrombosis in patients with active SARS-CoV-2 infections. Methods: We present seven SARS-CoV-2-positive patients from our institution who acutely developed thrombi in the aortoiliac arterial system (7/2020-1/2021). A systematic review of the literature on aortoiliac arterial thrombosis in patients with SARS-CoV-2 infections in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was also performed. The available data from all reported cases in the literature and at our institution were analyzed. Results: Thirty published articles and journal correspondences, including 52 patients, were reviewed and analyzed in addition to our institution's 7 cases. In total, 59 SARS-CoV-2-positive patients were found to have acute aortoiliac thrombosis. The abdominal aorta was the most frequent location for the development of a thrombus. Baseline demographics and medical comorbidities were not significantly different between the symptomatic and asymptomatic cohorts. Seventy-one percent of patients were symptomatic (lower limb ischemia: 75.0%, renal infarction: 20.0%, stroke: 12.5%, mesenteric ischemia: 10.0%). All patients with thrombus involving the ascending aorta, aortic bifurcation, or iliac artery developed thromboembolic or ischemic complications. All patients received systemic anticoagulation. Fifty-three percent of all patients were managed medically. Ninety-four percent of the asymptomatic patients were managed medically. One asymptomatic patient underwent endovascular aspiration of a mobile thrombus. Three (23.1%) deaths occurred in the asymptomatic cohort from hypoxic respiratory failure. Fourteen (36.8%) deaths occurred in the symptomatic cohort. The in-hospital mortality rate was 33.3% overall and 43.8% for patients with thrombi involving more than one aortoiliac segment. Conclusions: The presence of thrombi in the aortoiliac arterial system appears to be a poor prognostic indicator for patients with active SARS-CoV-2 infections. Medical management of patients with asymptomatic aortoiliac thrombi may be considered. The presence of thrombi involving the ascending aorta, aortic bifurcation, or iliac artery may warrant consideration for operative intervention due to the risk for thromboembolic or ischemic complications. Further study is needed to fully delineate the risk factors, optimal treatment, and outcomes of arterial thrombosis in the setting of SARS-CoV-2 infection.

Abstract Background Studies exploring risk factors for ankle fractures in adults are scarce, and with diverging conclusions. This study aims to investigate whether overweight, obesity and osteoporosis may be identified as risk factors for ankle fractures and ankle fracture subgroups according to the Danis-Weber (D-W) classification. Methods 108 patients ≥40 years with fracture of the lateral malleolus were included. Controls were 199 persons without a previous fracture history. Bone mineral density of the hips and spine was measured by dual-energy x-ray absorptiometry, and history of previous fracture, comorbidities, medication, physical activity, smoking habits, body mass index and nutritional factors were registered. Results Higher body mass index with increments of 5 gave an adjusted odds ratio (OR) of 1.30 (95% confidence interval (CI) 1.03–1.64) for ankle fracture, and an adjusted OR of 1.96 (CI 0.99–4.41) for sustaining a D-W type B or C fracture compared to type A. Compared to patients with normal bone mineral density, the odds of ankle fracture in patients with osteoporosis was 1.53, but the 95% CI was wide (0.79–2.98). Patients with osteoporosis had reduced odds of sustaining a D-W fracture type B or C compared to type A (OR 0.18, CI 0.03–0.83). Conclusions Overweight increased the odds of ankle fractures and the odds of sustaining an ankle fracture with possible syndesmosis disruption and instability (D-W fracture type B or C) compared to the stable and more distal fibula fracture (D-W type A). Osteoporosis did not significantly increase the odds of ankle fractures, thus suffering an ankle fracture does not automatically warrant further osteoporosis assessment.

Abstract Negative pressure wound therapy (NPWT) has been shown to improve clinical outcomes for children with burns by accelerating wound re-epithelialisation. Its effects on healthcare costs, however, remain poorly understood. The aim of this study was to evaluate the cost-effectiveness of NPWT from a healthcare provider perspective using evidence from the SONATA in C randomised controlled trial, in which 101 children with small-area burns were allocated to either standard care (silver-impregnated dressings) or standard care in combination with adjunctive NPWT. The primary outcome, time to re-epithelialisation, was assessed through a blinded photographic review. Resource usage and costs were prospectively recorded for each participant for up to 6 months. Incremental cost-effectiveness ratios and dominance probabilities were estimated and uncertainty quantified using bootstrap resampling. Mean costs per participant—including dressings, labour, medication, scar management, and theatre operations—were lower in the NPWT group (AUD $903.69) relative to the control group (AUD $1669.01). There was an 89% probability that NPWT was dominant, yielding both faster re-epithelialisation and lower overall costs. Findings remained robust to sensitivity analyses employing alternative theatre costs and time-to-re-epithelialisation estimates for grafted patients. In conclusion, adjunctive NPWT is likely to be a cost-effective and dominant treatment for small-area paediatric burns (ANZCTR.org.au:ACTRN12618000256279).

Sea spray aerosol (SSA) formation plays a major role in the climate system. The Antarctic Peninsula (AP) is affected by the greatest warming occurring in the Southern Ocean; changes in cryospheric and biological processes are being observed. Whilst there is some evidence that organic material produced by ice algae and/or phytoplankton in the high Arctic contributes to SSA, less is known about Antarctic Sea ice (sympagic) regions. To gain insight into the influence of Antarctic Sea ice biology and biogeochemistry on atmospheric aerosol, we report simultaneous water-air measurements made by means of in situ aerosol chamber experiments. For the first time, we present a methodology showing that the controlled plunging jet aerosol chamber settings do not cause major cell disruption on the studied sea ice ecosystems. Larger sea ice phytoplankton cells (>20 µm; mainly diatoms) tend to sediment at the bottom of the chamber (during the 24h experiment) and likely have a minor role on SSA production. When comparing four chamber experiments - we find that the two producing more SSA are the ones with highest abundance of nanophytoplankton cells (

Abstract miR-126 has been identified both as a tumor suppressor and an oncogene in different types of cancer. The aim of this study was to investigate the prognostic impact of miR-126-expression in colon cancer patients. Tumor tissue from 452 patients operated for stage I–III colon cancer was retrospectively collected and tissue microarrays were constructed. miR-126 expression was evaluated by in situ hybridization and analyzed using digital pathology. To isolate the compartment specific contribution of miR-126, tumor and adjacent tumor stroma were considered separately. In univariate analyses, high expression of miR-126 in tumor and stroma was related to increased disease-specific survival (p

Abstract Background Soil-transmitted helminths (STHs) are a major cause of poor health in low- and middle-income countries. In particular, hookworm is known to cause anaemia in children and women of reproductive age (WRA). One goal of the World Health Organization’s (WHO) 2030 roadmap for neglected tropical diseases is to reduce STH-related morbidity in WRA. As a minimal intervention, the WHO recommends deworming adolescent girls annually during human papilloma virus vaccination programmes and WRA during pregnancy and lactation. These routine interventions are low cost and can be implemented even by the most basic health services in endemic countries. In this study we use a cohort model to investigate the potential impact on STH-related morbidity in WRA. Results Annual deworming treatment of adolescent girls reduces the prevalence of moderate- and heavy-intensity infections in this age group by up to 60% in moderate transmission settings and by 12–27% in high transmission settings. Treatment of WRA during pregnancy and lactation on its own has a small (

Abstract Knowledge of hygroscopic properties is essential to prediction of the role of aerosol in cloud formation and lung deposition. Our objective was to introduce a new approach to classify and predict the hygroscopic growth factors (Gfs) of specific atmospheric sub-micrometre particle types in a mixed aerosol based on measurements of the ensemble hygroscopic growth factors and particle number size distribution (PNSD). Based on a non-linear regression model between aerosol source contributions from PMF applied to the PNSD data set and the measured Gf values (at 90% relative humidity) of ambient aerosols, the estimated mean Gf values for secondary inorganic, mixed secondary, nucleation, urban background, fresh, and aged traffic-generated particle classes at a diameter of 110 nm were found to be 1.51, 1.34, 1.12, 1.33, 1.09 and 1.10, respectively. It is found possible to impute (fill) missing HTDMA data sets using a Random Forest regression on PNSD and meteorological conditions.

Rajendra Prakash Maurya,1 Manish Kumar Prajapat,2 Virendra Pratap Singh,1 Meghna Roy,1 Ravina Todi,1 Sanjay Bosak,1 Sunit Kumar Singh,3 Sunil Chaudhary,4 Anil Kumar,5 Sunil R Morekar6 1Regional Institute of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India; 2Mahamaya Rajkiya Allopathic Medical College, Ambedkar Nagar, UP, India; 3Department of Molecular Biology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India; 4Department of Radiotherapy and Radiation Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India; 5Department of Statistics, Faculty of Science & Technology, Mahatma Gandhi Kashi Vidyapith, Varanasi, Uttar Pradesh, India; 6Apollo Specialty Hospital, Navi Mumbai, IndiaCorrespondence: Rajendra Prakash Maurya Email mauryarp_bhu@yahoo.comPurpose: To study the level of serum malondialdehyde (MDA), a biomarker of oxidative stress before and after chemotherapy in various ocular malignancies and to correlate its significance with clinicopathological parameters.Methods: Thirty two histopathologically confirmed cases of primary ocular malignancies were included in this longitudinal cohort study. Detailed clinicopathological assessment was done. Analysis of serum MDA level in the patient before and after chemotherapy was measured and its prognostic significance was analyzed.Results: Maximum cases were of eyelid malignancy (n=18, 56.2%) followed by retinoblastoma (18.8%) and OSSN (6, 18.8%). About 43.75% patients were in the advanced-stage. The tumor was histopathologically well-differentiated in 20 (62.5%) cases. Most common malignancy was sebaceous gland carcinoma of the eyelid (n=10,31.25%). Serum MDA level in patients were significantly higher than controls [5.5712± 0.32779 vs 2.5531± 0.08056 nmol/mL, p< 0.001]. Level was significantly reduced after chemotherapy (4.5146± 0.23209 nmol/mL). Serum MDA was maximum in cases of rhabdomyosarcoma (5.9450± 0.23335 nmol/mL) and retinoblastoma (5.7433± 0.14334 nmol/mL). It was minimum in basal cell carcinoma (5.3775± 0.17746 nmol/mL). Pre chemotherapy serum MDA level was significantly higher in patients having larger tumor (> 20mm, p< 0.001) and having lymph node metastasis than those without lymph node metastasis [5.8350± 0.17113 vs 5.4833± 0.32193 nmol/mL, p< 0.006]. No significant difference was observed in post chemotherapy serum MDA level as for as size of tumor (p=0.947) and histopathological differentiation (p=0.109) was concerned.Conclusion: The serum MDA level is a potential biomarker in primary ocular carcinoma to assess oxidative stress and its impact on response to chemotherapy.Keywords: malondialdehyde, chemotherapy, malignancy, oxidative stress, biomarker