Challenges with Quantifying Tire Road Wear Particles: Recognizing the Need for Further Refinement of the ISO Technical Specification

Environmental monitoring data for tire road wear particles are vastly limited compared to those for other microplastics, primarily due to analytical challenges with quantification. Recently, two ISO technical specifications have been released using pyrolysis GC-MS for quantification. However, these methods have major assumptions, including that the content of natural and synthetic rubber in tire tread is constant across formulations and that the pyrolysis products chosen are selective. This study analyzed a wide range of commercially available tires from Australia and Norway, using pyrolysis GC-MS to test these assumptions. The percent mass of synthetic rubber in tires (n = 39) was highly variable, ranging from <0.05 to 28%, when using the ISO-recommended pyrolysis product 4-vinylcyclohexene. The content varied between brands and models, demonstrating that formulations are highly variable and unknown. The styrene butadiene dimer and trimer pyrolysis products were also assessed, and the calculated synthetic rubber content was higher, had an even greater variability, and had no correlation with concentrations calculated using 4-vinylcyclohexene. Using the ISO method has the potential to underreport environmental concentrations of TRWPs by a factor of at least 5, suggesting the specification requires further refinement, and there is an immediate need for large-scale analysis of commercial tire treads and assessments of suitable pyrolysis products.acceptedVersio

Incidence and survival for cancer in children and young adults in the North of England, 1968–1995: a report from the Northern Region Young Persons’ Malignant Disease Registry

The Northern Region Young Persons’ Malignant Disease Registry records information on young people under 25 years old diagnosed with cancer in the Northern Region of England. Incidence and survival rates were calculated for children and young adults diagnosed with cancer between 1968 and 1995. There were 2099 (M:F 1.28:1) children (age 0–14 years) and 2217 (M:F 1.23:1) young adults (15–24 years) diagnosed with a first cancer between 1968 and 1995. The age-standardized rate (ASR) for childhood cancer was 121 per million 0 to 14 year-olds per year. For young adults the ASR was 175 per million 15 to 24 year-olds, per year. Incidence of childhood cancer increased over time at a rate of 12 extra cases per million children, per decade (P< 0.001). In young adults incidence rates increased by 16 extra cases per million 15 to 24 year-olds, per decade (P< 0.001). For childhood cancer 5-year survival was 42% for those diagnosed 1968–1977, 57% for 1978–1987 and 71% (95% CI 67–75) for 1988–1995. Survival for young adults over the three periods was 45%, 62% and 73% (95% CI 70–78) respectively. The cumulative risk of developing cancer before the age of 25 is 1 in 285. Over the 28-year period there were significant improvements in survival and modest increases in incidence in both children and young adults. © 2000 Cancer Research Campaig

Landscape of Epidermal Growth Factor Receptor Heterodimers in Brain Metastases

HER2+ breast cancer patients have an elevated risk of developing brain metastases (BM), despite adjuvant HER2-targeted therapy. The mechanisms underpinning this reduced intracranial efficacy are unclear. We optimised the in situ proximity ligation assay (PLA) for detection of the high-affinity neuregulin-1 receptor, HER2-HER3 (a key target of pertuzumab), in archival tissue samples and developed a pipeline for high throughput extraction of PLA data from fluorescent microscope image files. Applying this to a large BM sample cohort (n = 159) showed that BM from breast, ovarian, lung and kidney cancers have higher HER2-HER3 levels than other primary tumour types (melanoma, colorectal and prostate cancers). HER2 status, and tumour cell membrane expression of pHER2(Y1221/1222) and pHER3(Y1222) were positively, but not exclusively, associated with HER2-HER3 frequency. In an independent cohort (n = 78), BM had significantly higher HER2-HER3 levels than matching primary tumours (p = 0.0002). For patients who had two craniotomy procedures, HER2-HER3 dimer levels were lower in the consecutive lesion (n = 7; p = 0.006). We also investigated the effects of trastuzumab and pertuzumab on five different heterodimers in vitro: HER2-EGFR, HER2-HER4, HER2-HER3, HER3-HER4, HER3-EGFR. Treatment significantly altered the absolute frequencies of individual complexes in SKBr3 and/or MDA-MB-361 cells, but in the presence of neuregulin-1, the overall distribution was not markedly altered, with HER2-HER3 and HER2-HER4 remaining predominant. Together, these findings suggest that markers of HER2 and HER3 expression are not always indicative of dimerization, and that pertuzumab may be less effective at reducing HER2-HER3 dimerization in the context of excess neuregulin

Inhibition of beta-Catenin/CREB Binding Protein Signaling Attenuates House Dust Mite-Induced Goblet Cell Metaplasia in Mice

Excessive mucus production is a major feature of allergic asthma. Disruption of epithelial junctions by allergens such as house dust mite (HDM) results in the activation of β-catenin signaling, which has been reported to stimulate goblet cell differentiation. β-catenin interacts with various co-activators including CREB binding protein (CBP) and p300, thereby regulating the expression of genes involved in cell proliferation and differentiation, respectively. We specifically investigated the role of the β-catenin/CBP signaling pathway in goblet cell metaplasia in a HDM-induced allergic airway disease model in mice using ICG-001, a small molecule inhibitor that blocks the binding of CBP to β-catenin. Female 6- 8-week-old BALB/c mice were sensitized to HDM/saline on days 0, 1, and 2, followed by intranasal challenge with HDM/saline with or without subcutaneous ICG-001/vehicle treatment from days 14 to 17, and samples harvested 24 h after the last challenge/treatment. Differential inflammatory cells in bronchoalveolar lavage (BAL) fluid were enumerated. Alcian blue (AB)/Periodic acid–Schiff (PAS) staining was used to identify goblet cells/mucus production, and airway hyperresponsiveness (AHR) was assessed using invasive plethysmography. Exposure to HDM induced airway inflammation, goblet cell metaplasia and increased AHR, with increased airway resistance in response to the non-specific spasmogen methacholine. Inhibition of the β-catenin/CBP pathway using treatment with ICG-001 significantly attenuated the HDM-induced goblet cell metaplasia and infiltration of macrophages, but had no effect on eosinophils, neutrophils, lymphocytes or AHR. Increased β-catenin/CBP signaling may promote HDM-induced goblet cell metaplasia in mice

Flares and Proper Motions of Ground-State OH Masers in W75N

The star-forming region W75N hosts bright OH masers that are observed to be variable. We present observations taken in 2008 of the ground-state OH maser transitions with the Very Long Baseline Array (VLBA) and the Multi-Element Radio-Linked Interferometer Network (MERLIN) and with the Nancay Radio Telescope in 2011. Several of the masers in W75N were observed to be flaring, with the brightest 1720-MHz maser in excess of 400 Jy. The 1720-MHz masers appear to be associated with the continuum source VLA 1, unlike the bright flaring 1665- and 1667-MHz masers, which are associated with VLA 2. The 1720-MHz masers are located in an outflow traced by water masers and are indicative of very dense molecular material near the H II region. The magnetic field strengths are larger in the 1720-MHz maser region than in most regions hosting only main-line OH masers. The density falls off along the outflow, and the order of appearance of different transitions of OH masers is consistent with theoretical models. The 1665- and 1667-MHz VLBA data are compared against previous epochs over a time baseline of over 7 years. The median maser motion is 3.5 km/s, with a scatter that is comparable to thermal turbulence. The general pattern of maser proper motions observed in the 1665- and 1667-MHz transitions is consistent with previous observations.Comment: 14 pages, accepted for publication in MNRA

Comparisons of Aerosol Generation Across Different Musical Instruments and Loudness

Highlights•Aerosol number and mass concentrations measured during musical instrument playing.•A 1 dBA increase in sound pressure level yields ∼10% increase in number concentration.•Loudness of playing explains some but not all differences across instruments.•Musical instrument playing size distributions are consistent with those of breathing.•Simple songs sufficient to characterise aerosol emission during actual performance.AbstractRespiratory aerosols can serve as vectors for disease transmission, and aerosol emission is highly activity-dependent. COVID-19 severely impacted the performing arts due to concerns about disease spread by respiratory aerosols and droplets generated during singing and playing musical instruments. Aerosol generation from woodwind and brass performance is less understood compared to singing due to uncertainty about how the diverse range of musical instruments may impact respiratory aerosol concentrations and size distributions. Here, aerosol number and mass concentrations along with size distributions were measured for breathing, speaking, and playing four different woodwind and brass instruments by 23 professional instrumentalists. We find that a 1 dBA increase in sound pressure level corresponds to a ∼10% increase in aerosol number concentration. The aerosol size distribution is consistent with that of breathing. Differences in aerosol emission across musical instruments can be partly explained by the loudness of performance. Measuring aerosol generation from single notes or simple songs may be sufficient to characterise the aerosol emission range during actual performance, provided a range of loudnesses are accessed. These results provide insight into the factors contributing to aerosol emission during musical performance and facilitate risk assessments associated with infectious respiratory disease transmission in the performing arts

Trees and shrubs as sources of fodder in Australia

Experience with browse plants in Australia is briefly reviewed in terms of their forage value to animals, their economic value to the landholder and their ecological contribution to landscape stability. Of the cultivated species only two have achieved any degree of commercial acceptance (Leucaena leucocephala and Chamaecytisus palmensis). Both of these are of sufficiently high forage value to be used as the sole source of feed during seasonal periods of nutritional shortage. Both are also leguminous shrubs that establish readily from seed. It is suggested that a limitation in their present use is the reliance on stands of single species which leaves these grazing systems vulnerable to disease and insects. Grazing systems so far developed for high production and persistence of cultivated species involve short periods of intense grazing followed by long periods of recovery. Similar management may be necessary in the arid and semi-arid rangelands where palatable browse species are in decline

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

The mitochondrial genome of Angiostrongylus mackerrasae as a basis for molecular, epidemiological and population genetic studies

BACKGROUND: Angiostrongylus mackerrasae is a metastrongyloid nematode endemic to Australia, where it infects the native bush rat, Rattus fuscipes. This lungworm has an identical life cycle to that of Angiostrongylus cantonensis, a leading cause of eosinophilic meningitis in humans. The ability of A. mackerrasae to infect non-rodent hosts, specifically the black flying fox, raises concerns as to its zoonotic potential. To date, data on the taxonomy, epidemiology and population genetics of A. mackerrasae are unknown. Here, we describe the mitochondrial (mt) genome of A. mackerrasae with the aim of starting to address these knowledge gaps. METHODS: The complete mitochondrial (mt) genome of A. mackerrasae was amplified from a single morphologically identified adult worm, by long-PCR in two overlapping amplicons (8 kb and 10 kb). The amplicons were sequenced using the MiSeq Illumina platform and annotated using an in-house pipeline. Amino acid sequences inferred from individual protein coding genes of the mt genomes were concatenated and then subjected to phylogenetic analysis using Bayesian inference. RESULTS: The mt genome of A. mackerrasae is 13,640 bp in size and contains 12 protein coding genes (cox1-3, nad1-6, nad4L, atp6 and cob), and two ribosomal RNA (rRNA) and 22 transfer RNA (tRNA) genes. CONCLUSIONS: The mt genome of A. mackerrasae has similar characteristics to those of other Angiostrongylus species. Sequence comparisons reveal that A. mackerrasae is closely related to A. cantonensis and the two sibling species may have recently diverged compared with all other species in the genus with a highly specific host selection. This mt genome will provide a source of genetic markers for explorations of the epidemiology, biology and population genetics of A. mackerrasae