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Updated speciation of VOCs emitted from European-market aerosol dispenser consumer products
Get PDFAerosol dispensers are a popular format for consumer products that give rise to a substantial fraction of national volatile organic compound (VOC) emissions in high income countries (e.g. ∼6% to total annual UK VOC emissions). Given a high fraction of usage indoors these emissions can contribute to degraded indoor air quality in rooms with poor ventilation. Characterisation of emissions, both in terms of chemical speciation and amount released is currently poor. This paper presents a method for aerosol dispenser product VOC emission identification and quantification using a custom-built sampling chamber and complementary SIFT-MS and GC-FID-QMS techniques. UK aerosol dispenser production statistics are used to up-scale laboratory data to update the National Atmospheric Emissions Inventory speciation (NAEI) for total UK VOC emissions from aerosol dispenser products. Ethanol, n- and iso-butane, and propane were the most abundant VOCs emitted with some species, such as cyclomethicones, identified here that are not currently reported in national emissions inventories. Bottom up estimates of emissions indicate that total VOC emissions from aerosol products are currently overestimated in the UK by ∼37 ktonnes per year, particularly from carcare and cosmetics & toiletries sectors. Whilst there have been some widely reported detections of trace amounts of benzene in aerosol products in previous US studies, we do not find benzene in any of the 45 products tested here
Large-scale capsid-mediated mobilisation of bacterial genomic DNA in the gut microbiome
Get PDFTransducing bacteriophage and gene transfer agents (GTAs) are constrained by the structural limits of their capsids, which determine the maximum length of host DNA they can package. Here, we utilise nanopore sequencing of intact, capsid-packaged DNA molecules to recover full-length reads, thereby enabling the precise identification of encapsidated DNA and its bacterial origin. This approach was validated using well-characterised transducing systems and subsequently applied to faecal viromes from three healthy donors. Our analysis reveals that bacterial DNA encapsidation is widespread in the gut microbiome, with up to 5.4% of capsid-packaged DNA derived from bacterial genomes. Generalised transduction and GTA activity were especially prominent in Oscillospiraceae and Ruminococcaceae (e.g. Faecalibacterium spp.), while lateral transduction was observed in Bacteroides. Additionally, we detected induction of prophages in several highly prevalent gut bacterial taxa. These findings reveal the prevalence of bacterial DNA packaging via virus or virus-like capsids in the human gut, shedding light on the diverse mechanisms that drive this process
Improving 8 × 8 TeraFET array 2.85 THz-sensitivity by Liquid-Nitrogen cooling in a compact Cryostat
Get PDFCo-solute effects reveal the nature of weak forces governing GLP-1 oligomers stability
Get PDFGlucagon-like peptide-1 (GLP-1) is an incretin hormone widely used to manage diabetes and obesity, through its ability to regulate glucose homeostasis. Clinically relevant GLP-1 sequences form oligomeric states. Uncontrolled oligomer formation can drive fibril formation, posing challenges such as difficulty in controlling drug dosage, loss of activity, or toxicity, as the aggregates can be immunogenic and/or can form amyloids. Here, we used combined measurements of colloidal and conformational stability to characterise the intermolecular interactions underpinning the physical status of the GLP-1 7-37 amide (GLP-1am), at pharmaceutically relevant high concentrations. We focus on less explored conditions, around pH 5, mimicking the environment within native cellular secretory granules, where the hormone is also densely packed. Co-solutes allowed us to interfere with weak interactions affecting peptide self-association into soluble oligomers, and the conversion into aggregates and fibrils. We show that GLP-1am exists as soluble oligomers that assemble into nanosheets over the timescale of hours, in quiescent conditions. Aggregation proceeded via a nucleation-dependent mechanism, with its rate correlating to the magnitude of attractive intermolecular interactions. It was accelerated by ionic co-solutes, indicating a key role for screening of electrostatic interactions in modulating peptide–peptide attraction and assembly. The rate of aggregation was also pH-dependent, with rates being slower at pH 5 than pH 8. Notably, the addition of proline, as a co-solute, delayed the onset of GLP-1am aggregation in a pH-dependent manner. Thus, in quiescent conditions, GLP-1am forms discrete soluble oligomers capable of organising into ordered nanostructures rather than amyloid fibrils
Pedestrian alertness during the evening is not affected by lighting conditions typically used for road lighting
Get PDFA laboratory experiment was conducted to examine the impact of different lighting conditions on melatonin derived from saliva samples, alertness as measured through reaction time (RT) to an auditory stimulus and self-reported sleepiness. This experiment replicated previous work but with the inclusion of an extreme condition to test the null findings of that previous work. There were four lighting conditions as defined by illuminance at eye level and spectral power distribution. Three conditions, having photopic illuminances of 0.5 lx to 8 lx (melanopic equivalent daylight illuminance (EDI) values of 0.5 lx to 10.4 lx) repeated the range used in previous work: the fourth condition extended this to 83 lx (melanopic EDI approximately 100 lx), which is extreme compared to those conditions typical of road lighting. The time period over which measurements were conducted was intended to represent pedestrian activity in the evening. The results revealed a significant reduction in RT and significant decreases in melatonin and subjective sleepiness only with the extreme condition, but did not suggest that lighting conditions typically used for road lighting had a significant effect on any of the dependent variables
Social inequalities in patient outcomes after total hip replacement surgery for osteoarthritis in England: a population-based cohort study of the National Joint Registry
Get PDFBackground
Reducing health inequalities is of national importance. Total hip replacement (THR) is a commonly used elective surgical procedure. Few studies have examined area-level inequalities for a wide range of outcomes following THR. The aim of this study is to compare area-level socioeconomic differences in outcomes following primary THR surgery for osteoarthritis in England.
Methods and findings
This is a population-based prospective cohort study of the National Joint Registry (NJR). Data from the NJR were linked to national mortality, Hospital Episode Statistics and Patient Reported Outcome Measures (PROMs) databases for England from 2007 to 2017 with follow-up to 2023 for outcomes, for patients aged 50 years and over with osteoarthritis. Outcomes of 90-day mortality; 5-year revision rate; 6-month health complications; 1-year rehospitalisation and reoperation for orthopaedic indications; and patient-reported Oxford Hip Score (OHS), post-THR surgery were examined by area-level Index of Multiple Deprivation quintiles. Modified Poisson regression was adjusted for patient age, sex, body mass index, pre-operative physical state and comorbidity.
Among 448,184 patients with primary THR, mean age was 70 years (standard deviation: 9 years) and 61% were women. Patients from the most deprived group were more likely to die within 90 days of the operation compared to the least deprived group (adjusted rate ratio, RR: 1.25 (95% confidence interval (CI) [1.07, 1.46]); adjusted risk difference, RD: 9 (95% CI [2, 16]) per 10,000. Similarly, those from the most deprived group were more likely to experience complications (RR: 1.26 (95% CI [1.21, 1.32]); RD: 1.14% (95% CI [0.92, 1.36])); be rehospitalised (RR: 1.16 (95% CI [1.14, 1.19]; RD: 2.78% (95% CI [2.39, 3.17])) or reoperated (RR: 1.23 (95% CI [1.13, 1.33]); RD: 0.31% (95% CI [0.19, 0.44])) and report poorer OHS (adjusted score: −2.97 (95% CI [−3.10, −2.84]) N = 200,522). There was no variation by deprivation level for THR revision rates at 5 years (RR: 1.02 (95% CI [0.94, 1.10]); RD: 0.02% (95% CI [−0.10, 0.15])). The main study limitations are the lack of complete PROMs data, and the exclusion of self-funded patients or those with private insurance for THR procedures in independent hospitals.
Conclusions
Inequalities in several outcomes after THR are present in England by area-level deprivation. These findings are useful to inform shared decision-making for patients deciding whether to undergo hip replacement and to benchmark the effectiveness of policies which aim to reduce health inequalities following THR
Dynamins maintain nuclear envelope homeostasis and genome stability
Get PDFThe nuclear envelope is a protective barrier for the genome and a mechanotransduction interface between cytoplasm and nucleus, whose malfunction disrupts nucleocytoplasmic transport, compromises DNA repair, accelerates telomere shortening, and promotes genomic instability. Mechanisms governing nuclear envelope remodeling and maintenance in interphase and post-mitotic cells remain poorly understood. Here, we report a role for dynamins, a family of essential brain-enriched membrane- and microtubule-binding GTPases, in preserving nuclear envelope and genomic homeostasis. Cells lacking dynamins exhibit nuclear envelope dysmorphisms, including buds with long narrow necks where damaged DNA frequently accumulates. These cells also show impaired autophagic clearance, reduced levels of key DNA repair proteins, and aberrant microtubules. Nocodazole treatment restores nuclear morphology and reduces DNA damage. Collectively, the data reveal that dynamins promote nuclear envelope homeostasis and removal of damaged DNA via their GTPase activity and interaction with microtubules, providing insights into mechanisms that uphold genome stability and counteract aging-related pathologies
Functionality of symptoms and interpersonal communication in home video recordings of functional/dissociative versus epileptic seizures
Get PDFObjective
Conceptualizing functional/dissociative seizures (FDS) as resulting from dissociation, or conversion, we hypothesized that, compared to epileptic seizures (ES), FDS should carry more symbolic or communicative content and that this would allow observers to distinguish FDS from ES.
Methods
Three independent, epileptologically naive raters evaluated home videos of patients with confirmed diagnoses of either FDS or ES using a standardized form. The focus of the ratings was explicitly not on seizure semiology, but on verbal and nonverbal behavior, the role of proxies, interaction patterns, communication, emotional tone, symbolic content, and situational context.
Results
Of 598 home videos available from 183 patients, 215 ES and 95 FDS videos were suitable for analysis. No explicit symbolic communication was identified. FDS showed more passive, withdrawn behavior, and the postictal phase—captured more often than the ictal period—was particularly helpful for distinguishing FDS from ES. Interrater reliability was moderate. Features observed more commonly in FDS included closed eyes, recumbent posture, repetitive movements, reduced eye contact, responses to caring behavior, and occurrence in private settings. Raters perceived greater emotional distress in FDS and reported more distress watching these videos. Logistic regression based on all ratings correctly classified 94% of ES but only 32% of FDS.
Significance
Home video analysis captures important contextual and behavioral features of FDS and ES. The differential diagnostic reliability of lay raters' perceptions is limited. Findings suggest that FDS comprise passive rather than active appellative communication, likely reflecting emotional regulation processes. In contrast, in the home videos studied, ES patients exhibit greater postictal awareness and interaction than FDS patients, pointing to the relevance of the postictal phase for discriminating both seizure types. The results emphasize integrating environmental context and patient–caregiver interactions before, during, and after seizures to understand the functional significance of FDS in naturalistic, nonclinical settings
Ice‐Nucleating Particle and Cloud Ice Crystal Concentrations Associated With Developing Summertime Deep Convective Clouds in South‐Western USA
Get PDFIce-nucleating particles (INPs), essential for initiating primary ice production in many mixed-phase clouds, have only rarely been measured in air directly relevant for deep convective clouds. In July–August 2022 we used an aircraft to sample aerosol near developing deep convective clouds over Magdalena Mountain, New Mexico, USA. We observed INP concentrations consistently at the upper end of those typically observed in continental air with ∼0.01–0.5 L ‾¹ at −8°C. Vertically resolved sampling revealed a deep aerosol layer extending 3–4 km above ground level, in which INP concentrations only varied within an order of magnitude. Above this layer, low temperature INP (−15°C) remained abundant, despite having been collected in air with a lower aerosol concentration. Compositional analysis of filter aerosol showed mineral dusts dominated the surface area of aerosol larger than ∼800 nm, but the activity of the mineral alone cannot account for the observed INP concentrations. We suggest that these mineral dust particles are internally mixed with ice-nucleating biogenic components, as they would be in organic containing fertile soils, or there is an additional biogenic/biological ice-nucleating component(s) strongly enhancing the INP population over what would be expected for mineral dust alone. Finally, ice particle measurements in rising cloud turrets at progressively colder temperatures reveal that the temperature at which we first observed ice was consistent with the measured INP spectra
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