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Cannabis use severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.
Aims
Examine outcome data from the first 46 individuals to complete the CCP's intervention.
Method
The sample (N = 46) consisted of adults (aged ≥ 18) with psychosis under the care of the South London and Maudsley NHS Foundation Trust, referred to the CCP between January 2020 and February 2023, who completed their intervention by September 2023. Clinical and functional measures were collected before (T0) and after (T1) the CCP intervention (one-to-one sessions and peer group attendance). Primary outcomes were changes in the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) score and pattern of cannabis use. Secondary outcomes included T0–T1 changes in measures of delusions, paranoia, depression, anxiety and functioning.
Results
A reduction in the mean CUDIT-R score was observed between T0 (mean difference = 17.10, 95% CI = 15.54–18.67) and T1, with 73.91% of participants achieving abstinence and 26.09% reducing the frequency and potency of their use. Significant improvements in all clinical and functional outcomes were observed, with 90.70% being in work or education at T1 compared with 8.70% at T0. The variance in CUDIT-R scores explained between 34 and 64% of the variance in our secondary measures.
Conclusions
The CCP intervention is a feasible strategy to support cannabis use cessation/reduction and improve clinical and functional outcomes of people with psychotic disorders.
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Childhood bullying is a public health priority. We evaluated the effectiveness and costs of KiVa, a whole-school anti-bullying program that targets the peer context.
Methods
A two-arm pragmatic multicenter cluster randomized controlled trial with embedded economic evaluation. Schools were randomized to KiVa-intervention or usual practice (UP), stratified on school size and Free School Meals eligibility. KiVa was delivered by trained teachers across one school year. Follow-up was at 12 months post randomization. Primary outcome: student-reported bullying-victimization; secondary outcomes: self-reported bullying-perpetration, participant roles in bullying, empathy and teacher-reported Strengths and Difficulties Questionnaire. Outcomes were analyzed using multilevel linear and logistic regression models.
Findings
Between 8/11/2019–12/02/2021, 118 primary schools were recruited in four trial sites, 11 111 students in primary analysis (KiVa-intervention: n = 5944; 49.6% female; UP: n = 5167, 49.0% female). At baseline, 21.6% of students reported being bullied in the UP group and 20.3% in the KiVa-intervention group, reducing to 20.7% in the UP group and 17.7% in the KiVa-intervention group at follow-up (odds ratio 0.87; 95% confidence interval 0.78 to 0.97, p value = 0.009). Students in the KiVa group had significantly higher empathy and reduced peer problems. We found no differences in bullying perpetration, school wellbeing, emotional or behavioral problems. A priori subgroup analyses revealed no differences in effectiveness by socioeconomic gradient, or by gender. KiVa costs £20.78 more per pupil than usual practice in the first year, and £1.65 more per pupil in subsequent years.
Interpretation
The KiVa anti-bullying program is effective at reducing bullying victimization with small-moderate effects of public health importance.
Funding
The study was funded by the UK National Institute for Health and Care Research (NIHR) Public Health Research program (17-92-11). Intervention costs were funded by the Rayne Foundation, GwE North Wales Regional School Improvement Service, Children's Services, Devon County Council and HSBC Global Services (UK) Ltd.
Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.
Methods
We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately.
Results
Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia.
Conclusions
Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.
The UK Soft Drinks Industry Levy (SDIL) (announced in March 2016; implemented in April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order to understand how health policy can become established and resilient to opposition.
Design:
Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus.
Setting:
The United Kingdom Parliament
Participants:
N/A
Results:
Between the announcement (16/03/2016) – royal assent (26/04/2017), two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent – implementation (5/04/2018), one theme was identified 3: The SDIL worked – what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL.
Conclusions:
After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal.
Environmental sensors are crucial for monitoring weather conditions and the impacts of climate change. However, it is challenging to place sensors in a way that maximises the informativeness of their measurements, particularly in remote regions like Antarctica. Probabilistic machine learning models can suggest informative sensor placements by finding sites that maximally reduce prediction uncertainty. Gaussian process (GP) models are widely used for this purpose, but they struggle with capturing complex non-stationary behaviour and scaling to large datasets. This paper proposes using a convolutional Gaussian neural process (ConvGNP) to address these issues. A ConvGNP uses neural networks to parameterise a joint Gaussian distribution at arbitrary target locations, enabling flexibility and scalability. Using simulated surface air temperature anomaly over Antarctica as training data, the ConvGNP learns spatial and seasonal non-stationarities, outperforming a non-stationary GP baseline. In a simulated sensor placement experiment, the ConvGNP better predicts the performance boost obtained from new observations than GP baselines, leading to more informative sensor placements. We contrast our approach with physics-based sensor placement methods and propose future steps towards an operational sensor placement recommendation system. Our work could help to realise environmental digital twins that actively direct measurement sampling to improve the digital representation of reality.
Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.
Methods
Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.
Results
The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.
Conclusions
Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample.
Methods
Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of ‘Genetic’ models (solely fitted with PRS-SZ), ‘Environmental’ models (solely fitted with each environmental stressor), ‘Independent’ models (with PRS-SZ and each environmental factor), and ‘Interaction’ models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models.
Results
There were no genes-environment associations. PRS-SZ was associated with positive dimensions (β = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension.
Conclusions
This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.
Policies that promote conversion of antibiotics from intravenous to oral route administration are considered “low hanging fruit” for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Methods
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
Results
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Conclusions
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Evidence about the impact of the COVID-19 pandemic on the mental health of specific subpopulations, such as university students, is needed as communities prepare for future waves.
Aims
To study the association of proximity of COVID-19 with symptoms of anxiety and depression in university students.
Method
This trend study analysed weekly cross-sectional surveys of probabilistic samples of students from the University of British Columbia for 13 weeks, through the first wave of COVID-19. The main variable assessed was propinquity of COVID-19, defined as ‘knowing someone who tested positive for COVID-19’, which was specified at different levels: knowing someone anywhere globally, in Canada, in Vancouver, in their course or at home. Proximity was included in multivariable linear regressions to assess its association with primary outcomes, including 30-day symptoms of anxiety and/or depression.
Results
Of 1388 respondents (adjusted response rate of 50%), 5.6% knew someone with COVID-19 in Vancouver, 0.8% in their course and 0.3% at home. Ten percent were overwhelmed and unable to access help. Knowing someone in Vancouver was associated with an 11-percentage-point increase in the probability of 30-day anxiety symptoms (s.e. 0.05, P ≤ 0.05), moderated by gender, with a significant interaction of the exposure and being female (coefficient −20, s.e. 0.09, P ≤ 0.05). No association was found with depressive symptoms.
Conclusions
Propinquity of COVID-19 cases may increase the likelihood of anxiety symptoms in students, particularly among men. Most students reported coping well, but additional support is needed for an emotionally overwhelmed minority who report being unable to access help.
Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes.
Method:
Over 200 participants (ages 9–13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes.
Results:
For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (β) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9–10, 11–13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9–10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001.
Conclusion:
These findings suggest that in the 9–10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a $(20\pm 3)~\unicode[STIX]{x03BC}\text{m}$ X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
The PM10 (airborne particulate matter with aerodynamic diameter <10 mm) in Beijing has a distinct seasonality, with industrial, domestic and natural sources providing a heterogeneous cocktail of airborne particulate matter (PM). Collections were made during late winter, summer and high wind dust storms to determine composition and probable sources of this PM. The concentration of the PM during winter (174 μg m–3) was approximately four times higher than summer (37 μg m–3) with dust storms raising the concentration further (200 μg m–3). During the winter the PM was dominated by combustion products (66% filter area). During the summer combustion products and loess contributed ~35% to the filter area each, but during elevated wind speeds (>10 mph) loess completely dominated the collections (96% filter area). The majority of the PM10 collected was in the respirable (PM2.5) size range (winter 99.7%, summer 96.6%, dust storms 82.3%). The loess in Beijing comprises quartz, feldspar, calcite, chlorite and mica and is in the coarse silt to sand (20–60 mm) size range. The collections are therefore likely to be made up of finer silt and clay, primarily derived from of the erosion of cultivated land. Using a plasmid assay, the Beijing particulate matter was found to have little or no surface free radical activity.
Experiments were undertaken to determine the toxicity in the lung of dust generated by opencast coal mining. Since it was impractical to collect the large mass of actual opencast respirable dust required for the toxicity experiment, a surrogate dust with the same size distribution was manufactured (PSW). This surrogate dust had the same basic mineralogical composition as mineralogically characterized airborne dust collected from the welsh coal opencast pit at Park Slip West. Diesel exhaust particles (DEP), generated from mining vehicular and mechanical activity, contribute towards opencast particulate matter. Therefore, a second dust comprising of a 50/50 by weight mixture of the surrogate mineral dust and diesel soot was also examined (PSW + DEP). These dusts and DEP (weak biological reactivity) and a-quartz (high biological reactivity) were instilled into the lungs of healthy rats. The animals were sacrificed at 1, 6 and 11 weeks. Assessments of potential toxicity included lung to body weight ratios, acellular protein in lung lavage (markers of lung permeability) and total free cells (marker of inflammation). The surrogate opencast dust with or without DEP caused no significant increases in any of the parameters studied and as such was very similar to the weak biological effects of DEP alone. These effects contrasted sharply with those observed for the bioreactive mineral, quartz that induced rapid increases in permeability and a progressive inflammation. The use of a surrogate is less desirable then the real opencast mine dust, however, if as believed, the surrogate material is a representative mixture of the actual airborne dust around this opencast site, then these particles should show little or no short-term lung toxicity following inhalation.