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Background and Aims: Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core‐related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation. Methods: Patients with HBeAg‐negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation. End of treatment (EOT) and off‐treatment levels of serum HBcrAg, HBsAg, HBV RNA and HBV DNA were used to predict key clinical outcomes including hepatitis flare (ALT ≥5 × ULN and HBV DNA > 2000 IU/mL). The SCALE‐B score was calculated for the purposes of model validation. Results: HBcrAg was tested amongst 65 participants. The median age was 54 years, 54% were male and 83% were Asian. HBcrAg was detectable in 86% patients. HBcrAg level ≥4 log U/mL at EOT was predictive of hepatitis flare [8/10 (80%) vs. 17/55 (31%), p =.001]. The presence of either HBcrAg ≥4 log U/mL or detectable HBV RNA at EOT predicted for both biochemical relapse and hepatitis flare. The SCALE‐B model at EOT predicted for virological relapse, biochemical relapse, hepatitis flare and HBsAg loss in this cohort. An increase in the serum HBcrAg level off‐treatment was also associated with hepatitis flare. No participant with EOT HBcrAg level ≥4 log U/mL achieved HBsAg loss. Conclusions: High levels of serum HBcrAg predict for hepatitis flare after stopping NA therapy and low likelihood of HBsAg loss at week 96. People with high levels of serum HBcrAg are not suitable candidates for NA discontinuation. [ABSTRACT FROM AUTHOR]

Neuroanatomy is a notoriously challenging subject for medical students to learn. Due to the coronavirus disease‐19 (COVID‐19) pandemic, anatomical education transitioned to an online format. We assessed student performance in, and attitudes toward, an online neuroanatomy assessment compared to an in‐person equivalent, as a marker of the efficacy of remote neuroanatomy education. Participants in the National Undergraduate Neuroanatomy Competition (NUNC) 2021 undertook two online examinations: a neuroanatomically themed multiple‐choice question paper and anatomy spotter. Students completed pre‐ and post‐examination questionnaires to gauge their attitudes toward the online competition and prior experience of online anatomical teaching/assessment. To evaluate performance, we compared scores of students who sat the online (2021) and in‐person (2017) examinations, using 12 identical neuroradiology questions present in both years. Forty‐six percent of NUNC 2021 participants had taken an online anatomy examination in the previous 12 months, but this did not impact examination performance significantly (p > 0.05). There was no significant difference in examination scores between in‐person and online examinations using the 12 neuroradiology questions (p = 0.69). Fifty percent of participants found the online format less enjoyable, with 63% citing significantly fewer networking opportunities. The online competition was less stressful for 55% of participants. This study provides some evidence to suggest that student performance is not affected when undertaking online examinations and proposes that online neuroanatomy teaching methods, particularly for neuroradiology, may be equally as effective as in‐person approaches within this context. Participants perceived online examinations as less stressful but raised concerns surrounding the networking potential and enjoyment of online events. [ABSTRACT FROM AUTHOR]

Heterogeneous chemical cycles of pyrogenic nitrogen and halides influence tropospheric ozone and affect the stratosphere during extreme Pyrocumulonimbus (PyroCB) events. We report field‐derived N2O5 uptake coefficients, γ(N2O5), and ClNO2 yields, φ(ClNO2), from two aircraft campaigns observing fresh smoke in the lower and mid troposphere and processed/aged smoke in the upper troposphere and lower stratosphere (UTLS). Derived φ(ClNO2) varied across the full 0–1 range but was typically <0.5 and smallest in a PyroCB (<0.05). Derived γ(N2O5) was low in agricultural smoke (0.2–3.6 × 10−3), extremely low in mid‐tropospheric wildfire smoke (0.1 × 10−3), but larger in PyroCB processed smoke (0.7–5.0 × 10−3). Aged biomass burning aerosol in the UTLS had a higher γ(N2O5) of 17 × 10−3 that increased with sulfate and liquid water, but that was 1–2 orders of magnitude lower than values for aqueous sulfuric aerosol used in stratospheric models. Plain Language Summary: The injection of reactive material into Earth's atmosphere from fires affects atmospheric composition at regional and hemispheric scales. Reported stratospheric ozone depletion during extreme events, such as the 2020 Australian wildfires, illustrates one example of fire impacts and the role of heterogeneous (gas‐particle) processes. We report field quantification of rates and product yields from airborne observations of smoke. Extremely slow heterogeneous reaction rates on young smoke increase with transport and aging, but upper atmospheric values are still a factor of 10 slower than parameterizations used in stratospheric models. Heterogeneous production of ClNO2, a major lower atmospheric chlorine activation pathway, may be active on biomass burning aerosol in the upper atmosphere. Key Points: ClNO2 formation is active on biomass burning (BB) particles but decreases with transport to the upper troposphere and lower stratosphere (UTLS)N2O5 uptake coefficients are low on young BB smoke and increase with transport through a PyroCB and UTLS agingN2O5 uptake coefficients on aged BB particles in the UTLS are significantly lower than those used in model parameterizations [ABSTRACT FROM AUTHOR]

Background: Hypertension is a known risk factor for subarachnoid haemorrhage (SAH). The aim of this study was to describe the relationship between blood pressure and SAH using a large cohort study and perform a meta‐analysis of the published literature. Methods: Participants in the UK Biobank were followed up via electronic records until 31 March 2017. Cox proportional hazards models were used to analyse the association between baseline blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP] and MABP [mean arterial blood pressure]) and subsequent aneurysmal SAH. Linearity was assessed by comparing models including and excluding cubic splines. Electronic databases were searched from inception until 11 February 2022 for studies reporting on blood pressure and SAH. Results: A total of 500,598 individuals were included with 539 (0.001%) suffering from aneurysmal SAH. Nonlinear models including cubic splines visually appeared linear between SBP of 110 and 180 mmHg and there was minimal difference in fit between linear and nonlinear models. When values were stratified, those with SBP 120–130 mmHg were at higher risk compared to those with SBP <120 mmHg (hazard ratio [HR] 1.41 [1.02, 1.95]). The meta‐analysis demonstrated a similar increased risk of SAH in individuals with SBP 120–130 mmHg relative to those with <120 mmHg (HR 1.41 [1.17, 1.72]). A stepwise increase in risk was also seen at each subsequent threshold (130–140 mmHg: HR 1.85 [1.53, 2.24], 140–160 mmHg: HR 2.16 [1.57, 2.98], 160–180 mmHg: HR 2.81 [1.85, 4.29], >180 mmHg: HR 5.84 [1.94, 17.54]). Conclusions: The rate of SAH increases linearly with higher SBP in the general population and specifically appears lower in those with SBP <120 mmHg. [ABSTRACT FROM AUTHOR]

Background: Alanine aminotransferase (ALT) measurement is essential for evaluation of liver disease. We validated a novel rapid point‐of‐care (POC) test for ALT1 against laboratory ALT. Methods: Stored plasma samples from adults with chronic liver disease (Test cohort n = 240; Validation cohort n = 491) were analysed using the BioPoint® antigen immunoassay POC ALT1 lateral flow test, which provides quantitative ALT results (Axxin handheld reader) or semi‐quantitative results (visual read, cut off 40 IU/ml). The accuracy of POC ALT1 to detect ALT > 40 IU/L was determined by ROC analysis. In patients with chronic hepatitis B, treatment eligibility (EASL criteria) was determined using POC ALT1 and compared to laboratory ALT. Results: POC ALT1 test had good accuracy for laboratory ALT > 40 IU/L: AUROC 0.93 (95% CI: 0.89–0.96) in the Test cohort and AUROC 0.92 (95% CI: 0.88–0.95) in the Validation cohort. POC ALT1 cut off of 0.8 for ALT > 40 IU/L maximised sensitivity (97%) and specificity (71%) in the Test cohort (42% laboratory ALT > 40 IU/L) and yielded PPV 84% and NPV 91% in the Validation cohort (19% laboratory ALT > 40 IU/L). Semi‐quantitative POC ALT1 had good accuracy for laboratory ALT in the Validation cohort (AUROC 0.85, 95% CI: 0.81–0.99; sensitivity 77% and specificity 93%). Combined with HBV DNA and transient elastography, both quantitative and semi‐quantitative POC ALT1 tests had good accuracy for excluding hepatitis B treatment needs (sensitivity 96%, specificity 78% and NPV 99%). Conclusion: The POC ALT1 test had good accuracy for elevated ALT levels and for determining treatment eligibility among people with chronic hepatitis B. [ABSTRACT FROM AUTHOR]

Eradicating invasive species from islands is a proven method for safeguarding threatened and endangered species from extinction. Island eradications can deliver lasting benefits, but require large up‐front expenditure of limited conservation resources. The choice of islands must therefore be prioritised. Numerous tools have been developed to prioritise island eradications, but none fully account for the risk of those eradicated species later returning to the island: reinvasion.In this paper, we develop a prioritisation method for island eradications that accounts for the complexity of the reinvasion process. By merging spatially explicit metapopulation modelling with stochastic dynamic optimisation techniques, we construct a decision‐support tool that optimises conservation outcomes in the presence of reinvasion risk.We applied this tool to two different case studies—rat (Rattus rattus) invasions in the Seaforth archipelago in New Zealand, and cane toad (Rhinella marina) invasions in the Dampier archipelago in Australia—to illustrate how state‐dependent optimal policies can maximise expected conservation gains.In both case studies, incorporating reinvasion risk dramatically altered the optimal order of island eradications, and improved the potential conservation benefits. The increase in benefits was larger in Dampier than Seaforth (42% improvement versus 6%), as a consequence of both the characteristics of the invasive species, and the arrangement of the islands.Synthesis and applications. Our results illustrate the potential consequences of ignoring reinvasion risk. We recommend that reinvasion risk be explicitly included in any island eradication prioritisation involving an archipelago, particularly when some islands are close to the mainland. [ABSTRACT FROM AUTHOR]

HBV RNA is used as a marker of cccDNA transcription and is applicable in the setting of nucleos(t)ide analog (NA) treatment, which suppresses HBV DNA. Traditional assays for quantification of HBV RNA rely on labor‐intensive 3′RACE assays targeting the polyA tail. In this study, the high‐throughput Roche cobas®HBV RNA investigational assay was assessed on the Roche cobas® 6800 automated platform. Of 969 samples collected for a NA treatment cessation trial, and tested on the cobas assay, 249 were analyzed for sensitivity, reproducibility, sample type applicability, and results were compared to a RACE‐based assay. Results of 97 paired serum and plasma samples demonstrated an excellent correlation of 0.98. However, 14.5% of plasma samples yielded detectable (below the limit of quantification) results, when the paired serum was undetectable, and plasma was shown to yield a statistically significant (p < 0.001) greater mean 0.119 log10copies/ml. Quantification of 152 samples showed good correlation (0.91) between the cobas and RACE assays. The cobas assay demonstrated superior lower limit of quantification, 10 copies/ml, which resulted in detection of 13.2% more samples than the RACE assay. Reproducibility and linear range of the automated assay were also confirmed. The Roche cobas assay for HBV RNA is sensitive and highly recommended. [ABSTRACT FROM AUTHOR]

Nitrous acid (HONO) mixing ratios measured in aged wildfire smoke plumes were higher than expected from known homogeneous chemical reactions. In a representative smoke plume, intercepted hours to days downwind of the source, the missing HONO source was highly correlated to particulate nitrate photolysis and NO2 reactive uptake to particles. Using a multilinear regression involving these two sources, we could explain the missing HONO production in this plume (R2 = 0.77). The resulting fit parameters from this plume had good explanatory power (R2 = 0.64) for missing HONO production in other fire plumes. The mean enhancement factor for particulate nitrate photolysis relative to gas‐phase nitric acid photolysis was 63 and the mean NO2 reactive uptake coefficient to submicron aerosol surface area forming HONO was 4.9 × 10−4. Given the likelihood of other neglected secondary HONO sources, these values are upper‐limits, suggesting a need to revisit HONO formation mechanisms in aged wildfire smoke. Plain Language Summary: A river of smoke from multiple wildfires was sampled far downwind and served as a natural laboratory for evaluating sources of nitrous acid (HONO) in aged wildfire smoke. HONO photolysis is an important source of reactive oxidants that initiate chemical transformations of wildfire emissions. We demonstrate that sources of HONO from chemical processes, known as secondary HONO sources, can largely be explained by two processes – the photolysis of particulate nitrate and the reactive uptake of nitrogen dioxide (NO2) to smoke aerosol particles. High time resolution in situ observations of HONO and auxiliary measurements were used to map out variations in the missing HONO source across a wide span of wildfire characteristics. The results place an upper limit on the magnitude of HONO sources from particulate nitrate photolysis, and suggest that the heterogeneous NO2 reactive uptake to smoke particles could be more important than previous field studies have indicated. These findings demonstrate the existence of additional processes other than direct emissions responsible for HONO formation in fire smoke. This secondary HONO source could increase the oxidizing capacity of wildfire smoke plumes significantly downwind of the emission source and therefore affect the formation and lifetime of other secondary wildfire smoke components. Key Points: Secondary multi‐phase processes dominate daytime HONO levels in aged (>3 hr) fire smokeThe inferred strength of secondary HONO production is most correlated to NO2, aerosol surface area, and particulate nitrateWe find significantly weaker HONO formation from particulate nitrate photolysis than previous reports [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss. Methods: We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues. Conclusion: Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one‐third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission. [ABSTRACT FROM AUTHOR]

A new configuration of the Community Earth System Model (CESM)/Community Atmosphere Model with full chemistry (CAM-chem) supporting the capability of horizontal mesh refinement through the use of the spectral element (SE) dynamical core is developed and called CESM/CAM-chem-SE. Horizontal mesh refinement in CESM/CAM-chem-SE is unique and novel in that pollutants such as ozone are accurately represented at human exposure relevant scales while also directly including global feedbacks. CESM/CAM-chem-SE with mesh refinement down to ~14 km over the conterminous US (CONUS) is the beginning of the Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICAv0). Here, MUSICAv0 is evaluated and used to better understand how horizontal resolution and chemical complexity impact ozone and ozone precursors over CONUS as compared to measurements from five aircraft campaigns, which occurred in 2013. This field campaign analysis demonstrates the importance of using finer horizontal resolution to accurately simulate ozone precursors such as nitrogen oxides and carbon monoxide. In general, the impact of using more complex chemistry on ozone and other oxidation products is more pronounced when using finer horizontal resolution where a larger number of chemical regimes are resolved. Large model biases for ozone near the surface remain in the Southeast US as compared to the aircraft observations even with updated chemistry and finer horizontal resolution. This suggests a need for adding the capability of replacing sections of global emission inventories with regional inventories, increasing the vertical resolution in the planetary boundary layer, and reducing model biases in meteorological variables such as temperature and clouds. Plain Language Summary A new configuration of the Community Earth System Model (CESM)/Community Atmosphere Model with full chemistry (CAM-chem) supporting the capability of horizontal mesh refinement is developed. This configuration is the beginning of the Multi-Scale Infrastructure for Chemistry and Aerosols, which will create a unified infrastructure to model atmospheric chemistry and aerosols across scales in the Earth system. The capability in CESM/CAM-chem to use grids with horizontal mesh refinement is a novel advancement because the regional and global model components are seamlessly connected such that there is consistency in the physical and chemical processes between the components, which increases accuracy in prediction and efficiency in model development. This work evaluates this new model configuration over the conterminous US against measurements from five aircraft campaigns, which occurred during 2013. By evaluating model results against observations not only for ozone, but also ozone precursors, photolysis rate constants, temperature, planetary boundary layer height, etc., model skill at representing processes important for ozone formation and loss is inferred. Updates to horizontal resolution and chemistry improve simulated ozone and ozone precursors as compared to observations, but biases remain. The physical and chemical processes that are missing or erroneous in the model are highlighted to help prioritize future work. [ABSTRACT FROM AUTHOR]

Reactive chlorine and bromine species emitted from snow and aerosols can significantly alter the oxidative capacity of the polar boundary layer. However, halogen production mechanisms from snow remain highly uncertain, making it difficult for most models to include descriptions of halogen snow emissions and to understand the impact on atmospheric chemistry. We investigate the influence of Arctic halogen emissions from snow on boundary layer oxidation processes using a one‐dimensional atmospheric chemistry and transport model (PACT‐1D). To understand the combined impact of snow emissions and boundary layer dynamics on atmospheric chemistry, we model Cl2 and Br2 primary emissions from snow and include heterogeneous recycling of halogens on both snow and aerosols. We focus on a 2‐day case study from the 2009 Ocean‐Atmosphere‐Sea Ice‐Snowpack campaign at Utqiaġvik, Alaska. The model reproduces both the diurnal cycle and high quantity of Cl2 observed, along with the measured concentrations of Br2, BrO, and HOBr. Due to the combined effects of emissions, recycling, vertical mixing, and atmospheric chemistry, reactive chlorine is typically confined to the lowest 15 m of the atmosphere, while bromine can impact chemistry up to and above the surface inversion height. Upon including halogen emissions and recycling, the concentration of HOx (HOx = OH + HO2) at the surface increases by as much as a factor of 30 at mid‐day. The change in HOx due to halogen chemistry, as well as chlorine atoms derived from snow emissions, significantly reduce volatile organic compound lifetimes within a shallow layer near the surface. Key Points: A combination of factors including snow emissions, vertical mixing, and atmospheric chemistry explain surface Arctic halogen observationsSnow emissions of halogens impact atmospheric chemistry within a shallow layer near the surfaceSurface HOx concentrations are increased by up to a factor of 30 due to halogen chemistry [ABSTRACT FROM AUTHOR]

In recent years, there has been a rise in the number of people who are able to speak two or more languages. This has been paralleled by an increase in research related to bilingualism. Despite this, much of the neuroanatomical consequences and pathological implications of bilingualism are still subject to discussion. This review aims to evaluate the neuroanatomical structures related to language and to the acquisition of a second language as well as exploring how learning a second language can alter one's susceptibility to and the progression of certain cerebral pathologies. A literature search was conducted on the Medline, Embase, and Web of Science databases. A total of 137 articles regarding the neuroanatomical or pathological implications of bilingualism were included for review. Following analysis of the included papers, this review finds that bilingualism induces significant gray and white matter cerebral changes, particularly in the frontal lobes, anterior cingulate cortex, left inferior parietal lobule and subcortical areas, and that native language and acquired language largely recruit the same neuroanatomical structures with however, subtle functional and anatomical differences dependent on proficiency and age of language acquisition. There is adequate evidence to suggest that bilingualism offsets the symptoms and diagnosis of dementia, and that it is protective against both pathological and age‐related cognitive decline. While many of the neuroanatomical changes are known, more remains to be elucidated and the relationship between bilingualism and other neurological pathologies remains unclear. [ABSTRACT FROM AUTHOR]

Wildfire emissions affect downwind air quality and human health. Predictions of these impacts using models are limited by uncertainties in emissions and chemical evolution of smoke plumes. Using high‐time‐resolution aircraft measurements, we illustrate spatial variations that can exist within a plume due to differences in the photochemical environment. Horizontal and vertical crosswind gradients of dilution‐corrected mixing ratios were observed in midday plumes for reactive compounds and their oxidation products, such as nitrous acid, catechol, and ozone, likely due to faster photochemistry in optically thinner plume edges relative to darker plume cores. Gradients in plumes emitted close to sunset are characterized by titration of O3 in the plume and reduced or no gradient formation. We show how crosswind gradients can lead to underestimated emission ratios for reactive compounds and overestimated emission ratios for oxidation products. These observations will lead to improved predictions of wildfire emissions, evolution, and impacts across daytime and nighttime. Plain Language Summary: Wildfire emissions have large impacts on air quality and health in downwind communities. Previous research has shown that chemical reactions in fire plumes can be remarkably fast, which modifies the impact the smoke has downwind. In this work, we show how this chemistry happens faster on the edges versus the core of plumes emitted during midday. For plumes emitted near or after sunset, oxidation chemistry generally slows and remains nearly uniform across the plume. These variations in plume chemistry will impact how plumes are modeled, and how well we can predict downwind air quality impacts. Key Points: Spatial gradients are observed in dilution‐corrected mixing ratios of nitrous acid, ozone, and reactive organics in fresh wildfire plumesGradients evolve with time of day, as intensity of chemical aging varies relative to plume transport and mixingGradients should be considered when comparing plume models with measurements and estimating fire emissions from in situ observations [ABSTRACT FROM AUTHOR]

Wildland fires involve complicated processes that are challenging to represent in chemical transport models. Recent airborne measurements reveal remarkable chemical tomography in fresh wildland fire plumes, which remain yet to be fully explored using models. Here, we present a high‐resolution large eddy simulation model coupled to chemistry to study the chemical evolution in fresh wildland fire plume. The model is configured for a large fire heavily sampled during the Fire Influence on Regional to Global Environments and Air Quality field campaign, and a variety of airborne measurements are used to evaluate the chemical heterogeneity revealed by the model. We show that the model captures the observed cross‐transect variations of a number of compounds quite well, including ozone (O3), nitrous acid (HONO), and peroxyacetyl nitrate. The combined observational and modeling results suggest that the top and edges of fresh plume drive the photochemistry, while dark chemistry is also present but in the lower part of the plume. The model spatial resolution is shown to be very important as it may shift the chemical regime, leading to biases in O3 and NOx chemistry. Based on findings in this work, we speculate that the impact of small fires on air quality may be largely underestimated in models with coarse spatial resolutions. Plain Language Summary: Recent fire seasons in the United States have been record‐setting for many states. Several large wildfires raged across the entire west coast and lofted smoke plumes spread to the majority of the continental U.S. From a scientific perspective, wildland fires are fascinating due to their complexity. Fires emit heat, creating a plume of hot and turbulent air. The fire plume also contains many gases and aerosol particles produced from the burning and baking of a variety of fuels on the ground (trees, grasses, leaf litter and other fallen debris, etc.). Many of these gases and aerosol particles can impact climate, air quality, and human health. For this reason, most modern air quality and climate models now consider wildland fires. However, wildland fires are fundamentally challenging for these models, because many fine‐scale and large‐scale processes are entangled at the same time. In this work, we use a high‐resolution turbulence‐resolving numerical model to study the fine details in a wildland fire plume, with implications for large‐scale air quality and climate models. Key Points: Photochemistry is active at the edges of thick fire plumes, while dark chemistry is present in the lower part and below thick plumesHydroxyl radicals formed from nitrous acid drive the plume oxidation; nitrous acid may be produced on aerosolsModel resolution affects chemistry; sufficiently high spatial resolution is needed to capture the impacts of wildfires on air quality [ABSTRACT FROM AUTHOR]

This study investigates the use of airborne in situ measurements to derive transit time distributions (TTD) from the boundary layer (BL) to the upper troposphere (UT) over the highly convective tropical western Pacific (TWP). The feasibility of this method is demonstrated using 42 volatile organic compounds (VOCs) measured during the Convective Transport of Active Species in the Tropics (CONTRAST) experiment. Two important approximations necessary for the application are the constant chemical lifetimes for each compound and the representation of the BL source by the local CONTRAST data. To characterize uncertainties associated with the first approximation, we quantify the changes in derived TTDs when chemical lifetimes are estimated using conditions of the BL, UT, and tropospheric average. With the support of a trajectory model study in a companion paper, we characterize the BL source region contributing to the transport to the sampled UT. In addition to the TTDs derived using a regional average, we analyze the potential information content in locally averaged measurements to represent the dynamical variability of the region. Around 150 TTDs, derived using measurements on a ∼100 km spatial scale, show a distribution of mean and mode transit times consistent with the wide range of convective conditions encountered during the campaign. Two extreme cases, with the shortest and the near‐longest TTD, are examined using the dynamical background of the measurements and back trajectory analyses. The result provides physical consistency supporting the hypothesis that sufficient information can be obtained from measurements to resolve dynamical variability of the region. Plain Language Summary: In this study, we use measurements of the atmospheric chemical composition to derive vertical transport timescales over the tropical western Pacific, where convective processes dominate. A large suite of trace gases with a wide range of chemical lifetimes are measured from a research aircraft. The trace gas measurements are used to construct "transit time distributions," which capture the relative contributions of various transport pathways to the chemical composition of the upper troposphere in the study region. Results highlight the wealth of information in atmospheric chemical composition measurements, which is important not only for understanding chemistry of the atmosphere but also for quantifying aspects of atmospheric dynamics and circulation. Key Points: The approximations and uncertainties in deriving airborne chemical observation‐based tropospheric transit time distributions are examinedThe necessary approximation of trace gas lifetimes is found to be the largest source of uncertaintyThe method successfully identified a range of dynamical transport variability from aircraft measurements [ABSTRACT FROM AUTHOR]

Anatomists are well placed to tackle the transition from face‐to‐face to blended learning approaches as a result of the rapidly forced changes brought about by Covid‐19. The subject is extremely visual and has, therefore, previously been a target for the development of technology‐enhanced learning initiatives over the last ten years. Today's students have come to expect the integration of technology in the classroom and remotely. They adjust quickly to the innovative use of new applications and software and have begun to integrate it within their own workflow for note taking and study aids. Given the intense drive toward blended deliveries of anatomy as a result of the Covid‐19 pandemic, it is easy to picture how the benefits of working in partnership with students (in order to achieve many of these aims) would be possible, particularly in difficult subjects like neuroanatomy. In doing so, it provides anatomists with new opportunities to engage students in a way that aligns well with best practice frameworks for engaging students through partnership. The current United Kingdom guidelines set out by Advance HE (a professional membership organization for promoting excellence in higher education) strongly encourages the higher education community to seek out appropriate academic contexts where a balance of power can be struck between staff and student to create a community of practice. If such an approach can be fully embraced by anatomists, a strong argument can be made for seizing the opportunity to optimize the benefits of student partnership work in this discipline. [ABSTRACT FROM AUTHOR]

An estimated 18% of people living with chronic hepatitis B (CHB) in Australia were born in China. While guideline‐based care, including regular clinical monitoring and timely treatment, prevent CHB‐related cirrhosis, cancer and deaths, over three‐quarters of people with CHB do not receive guideline‐based care in Australia. This qualitative study aimed to identify enablers to engagement in CHB clinical management among ethnic Chinese people attending specialist care. Participants self‐identified as of Chinese ethnicity and who attended specialist care for CHB clinical management were interviewed in Melbourne in 2019 (n = 30). Semi‐structured interviews covered experiences of diagnosis and engagement in clinical management services, and advice for people living with CHB. Interviews were recorded with consent; data were transcribed verbatim and thematically analysed. Receiving clear information about the availability of treatment and/or the necessity of long‐term clinical management were the main enablers for participants to engage in CHB clinical management. Additional enablers identified to maintain regular clinical monitoring included understanding CHB increases risks of cirrhosis and liver cancer, using viral load indicators to visualize disease status in patient‐doctor communication; expectations from family, peer group and medical professionals; use of a patient recall system; availability of interpreters or multilingual doctors; and largely subsidized healthcare services. In conclusion, to support people attending clinical management for CHB, a holistic response from community, healthcare providers and the public health sector is required. There are needs for public health programmes directed to communicate (i) CHB‐related complications; (ii) availability of effective and cheap treatment; and that (iii) long‐term engagement with clinical management and its benefits. [ABSTRACT FROM AUTHOR]

Methods of assessment in anatomy vary across medical schools in the United Kingdom (UK) and beyond; common methods include written, spotter, and oral assessment. However, there is limited research evaluating these methods in regards to student performance and perception. The National Undergraduate Neuroanatomy Competition (NUNC) is held annually for medical students throughout the UK. Prior to 2017, the competition asked open‐ended questions (OEQ) in the anatomy spotter examination, and in subsequent years also asked single best answer (SBA) questions. The aim of this study is to assess medical students' performance on, and perception of, SBA and OEQ methods of assessment in a spotter style anatomy examination. Student examination performance was compared between OEQ (2013–2016) and SBA (2017–2020) for overall score and each neuroanatomical subtopic. Additionally, a questionnaire explored students' perceptions of SBAs. A total of 631 students attended the NUNC in the studied period. The average mark was significantly higher in SBAs compared to OEQs (60.6% vs. 43.1%, P < 0.0001)—this was true for all neuroanatomical subtopics except the cerebellum. Students felt that they performed better on SBA than OEQs, and diencephalon was felt to be the most difficult neuroanatomical subtopic (n = 38, 34.8%). Students perceived SBA questions to be easier than OEQs and performed significantly better on them in a neuroanatomical spotter examination. Further work is needed to ascertain whether this result is replicable throughout anatomy education. [ABSTRACT FROM AUTHOR]

The Western Wildfire Experiment for Cloud Chemistry, Aerosol Absorption, and Nitrogen (WE‐CAN) deployed the NSF/NCAR C‐130 aircraft in summer 2018 across the western U.S. to sample wildfire smoke during its first days of atmospheric evolution. We present a summary of a subset of reactive oxidized nitrogen species (NOy) in plumes sampled in a pseudo‐Lagrangian fashion. Emissions of nitrogen oxides (NOx = NO + NO2) and nitrous acid (HONO) are rapidly converted to more oxidized forms. Within 4 h, ∼86% of the ΣNOy is in the form of peroxy acyl nitrates (PANs) (∼37%), particulate nitrate (pNO3) (∼27%), and gas‐phase organic nitrates (Org N(g)) (∼23%). The average e‐folding time and distance for NOx are ∼90 min and ∼40 km, respectively. Nearly no enhancements in nitric acid (HNO3) were observed in plumes sampled in a pseudo‐Lagrangian fashion, implying HNO3‐limited ammonium nitrate (NH4NO3) formation, with one notable exception that we highlight as a case study. We also summarize the observed partitioning of NOy in all the smoke samples intercepted during WE‐CAN. In smoke samples intercepted above 3 km above sea level (ASL), the contributions of PANs and pNO3 to ΣNOy increase with altitude. WE‐CAN also sampled smoke from multiple fires mixed with anthropogenic emissions over the California Central Valley. We distinguish samples where anthropogenic NOx emissions appear to lead to an increase in NOx abundances by a factor of four and contribute to additional PAN formation. Key Points: NOx and HONO are rapidly converted to other species. The average e‐folding time (distance) for NOx is ∼90 min (∼40 km)In 4 h, PANs contribute ∼37% of the ΣNOy species in smoke; pNO3 is the second largest (∼27%) contributorIn 4 h, Org N(g) constitute a large portion (∼23%) of the ΣNOy in the plumes sample during WE‐CAN [ABSTRACT FROM AUTHOR]

Sulfur dioxide (SO2) is emitted in large quantities from coal‐burning power plants and leads to various harmful health and environmental effects. In this study, we use plume intercepts from the Wintertime INvestigation of Transport, Emission and Reactivity (WINTER) campaign to estimate the oxidation rates of SO2 under wintertime conditions and the factors that determine SO2 removal. Observations suggest that OH governs the rate SO2 oxidation in the eastern United States during winter. The range of mean oxidation rates during the day from power plants were 0.22–0.71%/hr, producing SO2 lifetimes of 13–43 days, if SO2 consumption is assumed to occur during 10.5 hr of daylight in cloudless conditions. Though most nighttime rate measurements were zero within uncertainty, there is some evidence of nighttime removal, which suggests alternate oxidation mechanisms. The fastest nighttime observed SO2 oxidation rate was 0.25±0.07%/hr, producing a combined day/night SO2 lifetime of 8.5–21 days. The upper limit of the oxidation rate (the mean+1σ of the fastest day and night observations) is 16.5%/day, corresponding to a lifetime of 6.1 days. The analysis also quantifies the primary emission of sulfate from power plants. The median mole percentage of SO4‐2 from observed plumes was 1.7% and the mean percentage sulfate was 2.8% for intercepts within 1 hr of transit to power plants. The largest value observed from close intercepts was over 7% sulfate, and the largest extrapolated value was 18%, based on intercepts further from their source and fastest observed oxidation rate. Key Points: The daytime conversion rate of SO2 to SO4‐2 was 0.22‐0.71%/hr in winter under clear‐sky conditions, with lifetimes of 140‐450 hrFor 10.5 hr of daylight, the upper limit of the oxidation rate is 16.5%/day, corresponding to a lifetime of 6.1 daysDirect emissions of SO4‐2 relative to total sulfur (SO2 + SO4‐2) had mean and median values of 1.7% and 2.8%, respectively [ABSTRACT FROM AUTHOR]

Within medical education a reduction in curriculum time for subjects, such as anatomy puts pressure on educators to ensure the same learning outcomes are conveyed in less time. This has the potential to impact negatively on student experience. Near‐peer teaching (NPT) is often praised as an effective revision tool, but its use as a frontline teaching resource remains unreported. The study explores the potential for NPT to promote delivery of learning outcomes and maximize student experience within a neuroanatomy module for second year medical students. The study occurred in three educational settings, (1) frontline NPT of cranial nerves, (2) revision session NPT of cranial nerves, and (3) NPT alongside faculty staff in laboratory‐based neuroanatomy practical exercises. For the first and second components, knowledge was measured using a pre‐ and post‐session test and student perception was ascertained with a questionnaire. For the third component, student perception was assessed with an end‐of‐module survey. The results show that overall, NPT was well received by learners. A significant knowledge gain was seen between the pre‐ and post‐session test of the frontline NPT session. The study presents evidence in favor of using NPTs to supplement the delivery of learning outcomes in a time and resource constrained curriculum. In particular, for the effective delivery of frontline material. Anat Sci Educ 0: 1–9. © 2018 American Association of Anatomists. [ABSTRACT FROM AUTHOR]

Summary: Background: Near‐peer teaching is used in anatomy education because of its benefits to the learner, teacher and faculty members. Despite the range of reports focusing on the learner, the advantages for the teacher, which are thought to include communication skills, subject knowledge and employability, are only beginning to be explored. Method: A questionnaire was distributed to the teachers involved in anatomy near‐peer teaching at the University of Southampton and Brighton and Sussex Medical School (BSMS). This questionnaire was designed using a rating scale of 0–10 to assess teacher perspectives on their level of knowledge, teaching skills and enjoyment of teaching. Free‐text responses determined the teachers’ motivation and perceived benefits from the teaching. Results: Twenty‐eight questionnaires were gathered (54.9% response rate), including 20 from Southampton and eight from BSMS. Long‐term knowledge retention and better understanding of the material were rated 8.1 and 7.9 out of 10, respectively. Eight responses were from currently practising doctors, who rated how much they now use their teaching skills as doctors as 8.9 out of 10. Of the eight doctors, seven gained points for their foundation programme applications as a direct result of near‐peer teaching. The most common motivator for engaging in teaching was to improve subject matter knowledge and the most common benefit was improved communication skills. There are numerous advantages to being a near‐peer teacher in medical school Discussion: There are numerous advantages to being a near‐peer teacher in medical school, which include knowledge improvement, transferrable professional skills and employability. These initial results support the hypothesised benefits to the teachers and provide a foundation for further longitudinal studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: International guidelines recommend screening for hepatitis B virus (HBV) infection prior to administration of rituximab, due to high risk of HBV reactivation in at‐risk patients. Aims: To determine: (i) adherence to the South Australian (SA) protocol for HBV screening; (ii) HBV prevalence in patients receiving rituximab; and (iii) outcomes of patients at risk of HBV reactivation. Methods: All patients commenced on rituximab at the six major SA public hospitals during a 12‐month period were included in the study. Adherence was assessed by documentation of both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) prior to initiation of rituximab. Patients were observed for a minimum of 6 months following rituximab initiation. Results: Four hundred and thirty eight patients were included in the study. The main indication for rituximab therapy was haematological malignancy (76.0%). Two hundred and nine (47.7%) failed to receive appropriate HBV screening, 86 (19.6%) had neither HBsAg nor HBcAb performed, and 119 (27.2%) had only HBsAg performed. The identified prevalence of at‐risk cases (either HBsAg‐ or HBcAb‐positive) within the study population was 4.6% (20/438 cases). One case of HBV reactivation was identified, but none led to acute liver failure, transplantation or death. Conclusions: Poor adherence to HBV screening protocols suggests the need for targeted clinician education and system redesign. While the rate of reactivation was low, the prevalence of at‐risk patients in this population was high and justifies further initiatives to increase adherence rates to HBV screening pre‐rituximab. [ABSTRACT FROM AUTHOR]

Abstract: We quantify the stratospheric injection of brominated very short‐lived substances (VSLS) based on aircraft observations acquired in winter 2014 above the Tropical Western Pacific during the CONvective TRansport of Active Species in the Tropics (CONTRAST) and the Airborne Tropical TRopopause EXperiment (ATTREX) campaigns. The overall contribution of VSLS to stratospheric bromine was determined to be 5.0 ± 2.1 ppt, in agreement with the 5 ± 3 ppt estimate provided in the 2014 World Meteorological Organization (WMO) Ozone Assessment report (WMO 2014), but with lower uncertainty. Measurements of organic bromine compounds, including VSLS, were analyzed using CFC‐11 as a reference stratospheric tracer. From this analysis, 2.9 ± 0.6 ppt of bromine enters the stratosphere via organic source gas injection of VSLS. This value is two times the mean bromine content of VSLS measured at the tropical tropopause, for regions outside of the Tropical Western Pacific, summarized in WMO 2014. A photochemical box model, constrained to CONTRAST observations, was used to estimate inorganic bromine from measurements of BrO collected by two instruments. The analysis indicates that 2.1 ± 2.1 ppt of bromine enters the stratosphere via inorganic product gas injection. We also examine the representation of brominated VSLS within 14 global models that participated in the Chemistry‐Climate Model Initiative. The representation of stratospheric bromine in these models generally lies within the range of our empirical estimate. Models that include explicit representations of VSLS compare better with bromine observations in the lower stratosphere than models that utilize longer‐lived chemicals as a surrogate for VSLS. [ABSTRACT FROM AUTHOR]

Formaldehyde (HCHO) directly affects the atmospheric oxidative capacity through its effects on HO x. In remote marine environments, such as the tropical western Pacific (TWP), it is particularly important to understand the processes controlling the abundance of HCHO because model output from these regions is used to correct satellite retrievals of HCHO. Here we have used observations from the Convective Transport of Active Species in the Tropics (CONTRAST) field campaign, conducted during January and February 2014, to evaluate our understanding of the processes controlling the distribution of HCHO in the TWP as well as its representation in chemical transport/climate models. Observed HCHO mixing ratios varied from ~500 parts per trillion by volume (pptv) near the surface to ~75 pptv in the upper troposphere. Recent convective transport of near surface HCHO and its precursors, acetaldehyde and possibly methyl hydroperoxide, increased upper tropospheric HCHO mixing ratios by ~33% (22 pptv); this air contained roughly 60% less NO than more aged air. Output from the CAM-Chem chemistry transport model (2014 meteorology) as well as nine chemistry climate models from the Chemistry-Climate Model Initiative (free-running meteorology) are found to uniformly underestimate HCHO columns derived from in situ observations by between 4 and 50%. This underestimate of HCHO likely results from a near factor of two underestimate of NO in most models, which strongly suggests errors in NO x emissions inventories and/or in the model chemical mechanisms. Likewise, the lack of oceanic acetaldehyde emissions and potential errors in the model acetaldehyde chemistry lead to additional underestimates in modeled HCHO of up to 75 pptv (~15%) in the lower troposphere. [ABSTRACT FROM AUTHOR]

It is important that clinicians are able to adequately assess their level of knowledge and competence in order to be safe practitioners of medicine. The medical literature contains numerous examples of poor self-assessment accuracy amongst medical students over a range of subjects however this ability in neuroanatomy has yet to be observed. Second year medical students attending neuroanatomy revision sessions at the University of Southampton and the competitors of the National Undergraduate Neuroanatomy Competition were asked to rate their level of knowledge in neuroanatomy. The responses from the former group were compared to performance on a ten item multiple choice question examination and the latter group were compared to their performance within the competition. In both cohorts, self-assessments of perceived level of knowledge correlated weakly to their performance in their respective objective knowledge assessments ( r = 0.30 and r = 0.44). Within the NUNC, this correlation improved when students were instead asked to rate their performance on a specific examination within the competition (spotter, rS = 0.68; MCQ, rS = 0.58). Despite its inherent difficulty, medical student self-assessment accuracy in neuroanatomy is comparable to other subjects within the medical curriculum. Anat Sci Educ 9: 488-495. © 2016 American Association of Anatomists. [ABSTRACT FROM AUTHOR]

Alcohol Dependence (AD) is a chronic relapsing disorder with high degrees of morbidity and mortality. While multiple neurotransmitter systems are involved in the complex symptomatology of AD, monoamine dysregulation and subsequent neuroadaptations have been long postulated to play an important role. Presynaptic monoamine transporters, such as the vesicular monoamine transporter 1 (VMAT1), are likely critical as they represent a key common entry point for monoamine regulation and may represent a shared pathway for susceptibility to AD. Excessive monoaminergic signaling as mediated by genetic variation in VMAT1 might affect functional brain connectivity in particular in alcoholics compared to controls. We conducted resting-state fMRI functional connectivity (FC) analysis using the independent component analysis (ICA) approach in 68 AD subjects and 72 controls. All subjects were genotyped for the Thr136Ile (rs1390938) variant in VMAT1. Functional connectivity analyses showed a significant increase of resting-state FC in 4 networks in alcoholics compared to controls (P < 0.05, corrected). The FC was significantly positively correlated with Alcohol Dependence Scale (ADS). The hyperfunction allele 136Ile was associated with a significantly decreased FC in the Default Mode Network, Prefrontal Cortex Network, and Executive Control Network in alcohol dependent participants (P < 0.05, corrected), but not in controls. Our data suggest that increased FC might represent a neuroadaptive mechanism relevant to AD that is furthermore mediated by genetic variation in VMAT1. The hyperfunction allele Thr136Ile might have a protective effect that is, in particular, relevant in AD by mechanism of increased monoamine transport into presynaptic storage vesicles. [ABSTRACT FROM AUTHOR]

There is increasing recognition of multiprofessional learning in anatomy and its role in medical and healthcare professions. This study utilized two components to investigate anatomy interprofessional education (AIPE) in the United Kingdom and Ireland. First, a survey involving qualitative and quantitative components asked Heads of Anatomy to report on their institutions' uptake of AIPE. Second, a series of case studies explored the experiences of students by using evaluation forms and an in-depth analysis of thematic concepts to understand the learners' perspectives on designing and delivering AIPE. Out of the 13 institutions that took part in the survey, eight did not offer an AIPE program. Between the remaining five institutions that deliver AIPE programs, 10 different modules are offered with the majority involving healthcare professions. The AIPE component is rated highly by students. The themes from the case studies highlight how valuable AIPE is from the student perspective both in terms of engaging them in anatomy as well as in the broader skills of teamwork and communication. The case studies also revealed how AIPE can be engaging for groups of students who might not have previously had access to cadaveric anatomy, for example, engineers and archeologists. The results of this study have implications for curriculum design in medicine and healthcare but also for further engagement of professional groups from non-healthcare backgrounds. [ABSTRACT FROM AUTHOR]

Background Liver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 ( MCP-1/ CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process. Methods We studied cerebrospinal fluid ( CSF) levels of MCP-1 as well as interleukin-1 β and tumor necrosis factor- α in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as markers of alcohol-related liver inflammation. Results Compared to healthy volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4 and day 25 ( p < 0.0001). Using multiple regression analysis, we found that MCP-1 concentrations were positively associated with the liver enzymes gamma glutamyltransferase ( GGT; p = 0.03) and aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/GOT; p = 0.004). Conclusions These preliminary findings are consistent with the hypothesis that neuroinflammation as indexed by CSF MCP-1 is associated with alcohol-induced liver inflammation, as defined by peripheral concentrations of GGT and AST/ GOT. [ABSTRACT FROM AUTHOR]

Near-peer teaching involves more experienced students acting as tutors and has been widely used in anatomy education. This approach has many advantages for the learner due to the social and cognitive congruence they share with the teacher, however, the influence of distance between the teacher and learner on these congruences has yet to be explored. The aim of this study was to compare the attitudes and perceptions of the student learner towards neuroanatomy review sessions taught by either a senior medical student or a junior doctor. The students were randomly assigned to an allocated tutor. All tutors used standardized material and had access to identical resources. The type of allocated tutor was swapped between the two teaching sessions and 99 student feedback forms were collected in total. The rating for the overall quality of the teaching session was not significantly different between the junior doctors and senior medical students ( P = 0.11). However, criteria closely relating to social and cognitive congruence such as 'enjoyment of the session,' 'delivery of the teaching,' and 'was it a good use of time' were all rated significantly higher for the senior medical students ( P < 0.05). The results of this study suggest that small increases in distance along the near-peer teaching spectrum have an impact upon the student's perception of their learning experience. While all teachers were suitable role models it appears that junior doctors are too far removed from their own undergraduate experiences to share congruences with pre-clinical medical students. Anat Sci Educ 7: 242-247. © 2013 American Association of Anatomists. [ABSTRACT FROM AUTHOR]

Background: Near-peer teaching involves students being taught by more senior students and draws on their similar knowledge base and shared experiences. It has been used previously for teaching gross anatomy, but has not yet been reported specifically for neuroanatomy. At the University of Southampton there is no formal neuroanatomy teaching during the clinical years, and so a near-peer teaching programme was developed to support students, learning in between attending their clinical attachments. Methods: A series of seven sessions were organised and delivered by two medical students throughout the 2010/11 academic year, and each session was evaluated by using participant feedback forms. Results: Sixty feedback forms were returned by the students, giving an average rating for the overall quality of the sessions of 4.3 out of 5.0. There was an 18 per cent increase in the student's perceived level of knowledge (p < 0.0001) as a result of our near-peer teaching sessions. The most common feedback received from our students related to the availability of handouts and expressions of gratitude. Discussion: The results from this teaching development support the use of near-peer teaching in neuroanatomy. In this article we provide some evidence to suggest that students feel more confident with neuroanatomy after attending these sessions, and describe some unique advantages of this teaching programme over sessions led by faculty staff. The wider benefits to both faculty staff and student teachers are also considered. [ABSTRACT FROM AUTHOR]

Convective transport from the marine boundary layer to the upper troposphere (UT) is investigated using airborne in situ measurements of chemical species over the tropical western Pacific. Using 42 volatile organic compounds with photochemical lifetimes ranging from shorter than a day to multiple decades, we derive a transit time spectrum G(t) and the associated modal and mean transit times for the UT air mass over the convectively dominant tropical western Pacific region. G(t) describes relative contributions of air masses transported from the marine boundary layer to the UT via all transport paths with different transit times. We further demonstrate that the volatile organic compound‐derived transit time scale is broadly comparable to that estimated from convective mass flux. The observation‐based transit time spectrum not only provides insights into convective transport pathways, but also has the potential to serve as an effective diagnostic for evaluating the representation of convective transport in global models. Plain Language Summary: Tropical deep convection is an important mechanism whereby air mass and chemical species are transported from near the surface to the upper troposphere and lower stratosphere. This transport process is difficult to quantify by observations or represent in models because of the small spatial scales and short temporal scales involved. In this study, we present a method to characterize convective transport using the framework of transit time spectrum, which describes the relative contributions of different transport paths with different transit times. We demonstrate that convective transport transit time spectrum can be derived using airborne in situ measurements of chemical species with a wide range of lifetimes, and we illustrate the wealth of information they provide for quantifying transport processes. This analysis method has the potential to serve as a unique diagnostic for evaluating the representation of convective transport in global models. Key Points: Airborne in situ measurements of VOCs with a wide range of lifetimes are used to quantify a convective‐transport transit time spectrumThe transit time scale derived from VOC measurements is broadly comparable to that estimated from convective mass fluxThe estimated transit time spectrum has the potential to serve as an effective diagnostic for evaluating convective transport in CCMs [ABSTRACT FROM AUTHOR]