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Background In the context of global climate change, studies have focused on the ambient temperature and mortality of cardiovascular diseases (CVDs). However, little is known about the effect of ambient temperature on year of life lost (YLL), especially the life loss per death caused by ambient temperature. In this study, we aimed to assess the relationship between ambient temperature and life loss and estimate the impact of ambient temperature on life loss per death. Methods We collected daily time series of mortality and meteorological data from 70 locations in Hunan province, central China, in periods ranging from Jan. 1, 2013, to Dec. 31, 2017. Crude rates of YLL were calculated per 100,000 people per year (YLL/100,000 population) for each location. A distributed lag nonlinear model and multivariate meta-regression were used to estimate the associations between ambient temperature and YLL rates. Then, the average life loss per death attributable to ambient temperature was calculated. Results There were 711,484 CVD deaths recorded within the study period. The exposure-response curve between ambient temperature and YLL rates was inverted J or U-shaped. Relative to the minimum YLL rate temperature, the life loss risk of extreme cold temperature lasted for 10 to 12 days, whereas the risk of extreme hot temperature appeared immediately and lasted for 3 days. On average, the life loss per death attributable to non-optimum ambient temperatures was 1.89 (95% CI, 1.21-2.56) years. Life loss was mainly caused by cold temperature (1.13, 95% CI, 0.89‑1.37), particularly moderate cold (1.00, 95% CI, 0.78‑1.23). For demographic characteristics, the mean life loss per death was relatively higher for males (2.07, 95% CI, 1.44‑2.68) and younger populations (3.72, 95% CI, 2.06‑5.46) than for females (1.88, 95% CI, 1.21-2.57) and elderly people (1.69, 95% CI, 1.28-2.10), respectively. Conclusions We found that both cold and hot temperatures significantly aggravated premature death from CVDs. Our results indicated that the whole range of effects of ambient temperature on CVDs should be given attention.

Children show a distinct presentation of COVID‐19, characterized by a lower incidence and mild phenotype, but the reason for this is still unknown. The angiotensin‐converting enzyme 2 (ACE2) functions as the primary cell entry receptor for Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and is thought to cause distinct clinical features between children and old people. The primary purpose of this study was to determine whether differences exist in the level of expression and distribution of ACE2 between neonatal and adult rat lungs. The lung tissues from rats of various ages were used to investigate the expression patterns of ACE2. Western blot, immunohistochemistry, and immunofluorescence were used to quantify or identify the localization of ACE2 in rat lungs. ACE2 was homogenously expressed in fewer alveolar type II (AT2) cells in the neonatal lung, with no polarization to the alveolar space and additional expression in pulmonary endothelium when compared to adult rat lungs. These findings suggest that the patterns of ACE2 distribution and cellular localization in rat lungs change with age., Here, we examined whether differences exist in the level of expression and distribution of ACE2 between neonatal and adult rat lungs. We found that ACE2 was homogenously expressed in fewer alveolar type II cells in the neonatal lung, with no polarization to the alveolar space and additional expression in pulmonary endothelium when compared to the adult rat lung.

ObjectivesThis study aimed to identify the relationship among proactive personality, psychological safety, academic self-efficacy and critical thinking, and to further explore whether psychological safety and academic self-efficacy could be a moderator in the association between proactive personality and critical thinking among Chinese medical students.Materials and methodsThe cross-sectional study was carried out from October to December 2020 in China. Totally, 5,920 valid responses were collected at four Chinese medical universities. Critical thinking, proactive personality, psychological safety, academic self-efficacy and demographic factors were assessed through questionnaires. Hierarchical multiple regression was used to identify interrelationship clusters among variables. Simple slope analyses were performed to explore the moderating effects of psychological safety and academic self-efficacy.ResultsThe mean score of critical thinking among medical students was 3.85 ± 0.61. Proactive personality, psychological safety, and academic self-efficacy were shown to be important factors for critical thinking. Psychological safety and academic self-efficacy moderated the association between proactive personality and critical thinking. A simple slope analysis showed that high psychological safety and academic self-efficacy weakened the impact of proactive personality on critical thinking.ConclusionMost medical students surveyed in China might have relatively high levels of critical thinking. Psychological safety and academic self-efficacy moderated the association between proactive personality and critical thinking. More interventions related to psychological safety and academic self-efficacy will be helpful to improve critical thinking among Chinese medical students.

(1) Background: Chinese physicians have encountered serious physical and verbal attacks in recent decades due to poor patient–physician relationships, leading to a broad spectrum of negative consequences. This study aims to assess the status of intergroup threats perceived by physicians and explore its association with organizational psychology, behavior, and well-being during the COVID-19 pandemic. (2) Methods: We conducted a cross-sectional online survey with physicians from November to December 2020 in three provinces: Heilongjiang Province, Henan Province, and Zhejiang Province, in China. A total of 604 physicians were recruited to complete an anonymous questionnaire. There were 423 valid questionnaires. (3) Results: We developed a 25-item intergroup threat scale with four dimensions: interest damage, performance impairment, value derogation, and unjust sentiment. Internal consistency reliability analyses showed that the four dimensions and overall scale exhibited high internal consistency (0.756–0.947). Additionally, the average scores for physicians’ perceived overall intergroup threat, interest damage, performance impairment, value derogation, and unjust sentiment were 4.35 ± 0.51, 4.24 ± 0.73, 4.33 ± 0.58, 4.22 ± 0.65, and 4.53 ± 0.55, respectively. Moreover, this study shows that the intergroup threats perceived positively by physicians were associated with psychological stress (β = 0.270, p < 0.01), emotional exhaustion (β = 0.351, p < 0.01), turnover intention (β = 0.268, p < 0.01), and defensive medical behavior (β = 0.224, p < 0.01), and were negatively associated with job satisfaction (β = −0.194, p < 0.01) and subjective well-being (β = −0.245, p < 0.01). (4) Conclusions: The newly developed scale in this study is a reliable tool for measuring intergroup threats perceived by Chinese physicians. Physicians in China were suffering high-level intergroup threats during the anti-COVID-19 pandemic, which has a significant impact on damage to organizational psychology, behavior, and well-being. Intergroup threats perceived by physicians not only enlarged the risk of emotional exhaustion and psychological stress but also threatened organizational well-being. Moreover, greater intergroup threats were associated with a lower job satisfaction, more frequent defensive medical behavior, and a higher turnover intention for physicians. The results of this study suggest that essential intervention and governance measures should be considered to protect physicians’ well-being and benefits in China, which are urgently needed.

Heavy metals in cultivated soil may migrate and transform through the food chain to harm the ecological environment and human health. At present, the ecological environment and human health risks of heavy metals in cultivated soil in Lanzhou city remain unclear, which impacts the effective management and control of heavy metals. The potential ecological risk hazard index was used to evaluate the ecological environmental risks of As, Cd, Cr, Hg, and Pb in the surface soil of cultivated land in Lanzhou, and the health risk model proposed by USEPA and the recommended standard were used to evaluate their human health risk. The main factors influencing the spatial differentiation of human health risk were explored by using geographic detectors. The risk of heavy metals to the ecological environment of the cultivated land surface soil in the study area was mainly medium (65.25%), and small portions were low (13.80%) and high (20.95%). The low-risk areas were mainly located in the southeast of Yongdeng County, the middle and north of Yuzhong County, and the southwest of Gaolan County. Moderate risk areas were distributed in three counties and five districts. The high-risk areas were located in the north and southeast of Yongdeng County, the south of Chengguan District, the northeast of Qilihe, the east of Xigu District, and the middle of Yuzhong County. The non-carcinogenic and carcinogenic risks of five types of heavy metal exposure pathways were as follows:oral ingestionskin contactrespiratory ingestion; generally speaking, children were at higher risk than adults. The non-carcinogenic risk in children was higher than that in adults; however, there was no such risk for local residents, as they were all less than 1. At the same time, the carcinogenic risk of As was greater than 1×10

BackgroundNurses working in the intensive care unit (ICU) clung tenaciously to their job during the COVID-19 pandemic in spite of enduring stressed psychological and physical effects as a result of providing nursing care for the infected patients, which indicates that they possessed a high degree of professionalism and career calling. The aim of this study was to explain the associations between resilience, thriving at work, and ethical leadership influencing the calling of ICU nurses.MethodsFrom December 2020 to January 2021 during the COVID-19 pandemic, a cross-sectional survey of 15 provinces in China was conducted using an online questionnaire. A total of 340 ICU nurses (effective response rate: 64.89%) completed sufficient responses to be used in the study. Sociodemographic factors, job demographic factors, resilience, calling, thriving at work, and ethical leadership were assessed using the questionnaire. General linear modeling (GLM), hierarchical linear regression (HLR) analysis, and generalized additive model (GAM) were performed to examine all the considered research hypotheses.ResultsResilience was positively and significantly associated with calling. Moreover, thriving at work partially mediated the relationship between resilience and calling. The indirect effect of resilience on calling was 0.204 (p < 0.0001), and the direct effect of resilience on calling through thriving at work was 0.215 (p < 0.0001). The total effect of resilience on calling was 0.419 (p < 0.0001). In addition, ethical leadership played a moderating role in the relationship between resilience and calling (β = 0.16, p < 0.05).ConclusionGreater resilience can positively predict increased calling among Chinese ICU nurses during the COVID-19 pandemic. Moreover, thriving at work is a mechanism that partly transmits the positive effects of resilience on calling. Overall, nurses possessing greater resilience tend to maintain thriving at work in the face of such adversity, further resulting in subsequently increased calling. Besides, findings suggest that there is stronger influence of resilience on calling among nurses working in an organization managed by an ethical leader. The current findings may offer two insights for nursing practitioners and policymakers in the postpandemic world. First, resilience training and intervention are necessary to foster nurses' sense of thriving at work in the nursing industry, further promoting career calling. Second, better training and effort on the development of ethical leadership for leaders in nursing practice are essential to encourage followers to engage in social learning of ethical behaviors and abiding by normatively appropriate conduct, further enacting prosocial values and expressing moral emotions.

Moromycin B (Mor B), saquayamycin B

Several immune checkpoint blockades (ICBs) capable of overcoming the immunosuppressive roles of the tumor immune microenvironment have been approved by the US Food and Drug Administration as front-line treatments of various tumor types. However, due to the considerable heterogeneity of solid tumor cells, inhibiting one target will only influence a portion of the tumor cells. One way to enhance the tumor-killing efficiency is to develop a multiagent therapeutic strategy targeting different aspects of tumor biology and the microenvironment to provide the maximal clinical benefit for patients with late-stage disease. One such strategy is the administration of anti-PD1, an ICB, in combination with the humanized monoclonal antibody bevacizumab, an anti-angiogenic therapy, to patients with recurrent/metastatic malignancies, including hepatocellular carcinoma, metastatic renal cell carcinoma, non-small cell lung cancer, and uterine cancer. Radiotherapy (RT), a critical component of solid cancer management, has the capacity to prime the immune system for an adaptive antitumor response. Here, we present an overview of the most recent published data in preclinical and clinical studies elucidating that RT could further potentiate the antitumor effects of immune checkpoint and angiogenesis dual blockade. In addition, we explore opportunities of triple combinational treatment, as well as discuss the challenges of validating biomarkers and the management of associated toxicity.

BACKGROUND Peliosis hepatis (PH) is a rare benign lesion of vascular origin with a pathological characteristic of multiple blood-filled cavities in the liver parenchyma. It is commonly misdiagnosed due to its lack of specificity in clinical presentation and laboratory test results. Herein, a case of a patient with PH who was misdiagnosed with hepatic echinococcosis before operation to remove the lesions was analyzed, with an emphasis on the computed tomography and magnetic resonance imaging characteristics of PH. CASE SUMMARY We outline the case of a 40-year-old Chinese female who was admitted with aggravated abdominal pain with fever for 1 wk. Ultrasound examination at the local hospital indicated hepatic echinococcosis. However, discordance between imaging diagnosis, clinical history and laboratory examinations in our hospital. Subsequently, the patient was pathologically confirmed as having PH-like changes, which recurred 1 year after operation removal of the lesion. CONCLUSION Our objective is to highlight the imaging diagnostic value of PH.

Purpose: To investigate the affinity of a bis-indole alkaloid - voacamine from Voacanga Africana Stapf for IL-2Rα - and its immunosuppressive effect on concanavalin A-induced T cell proliferation and lipopolysaccharide -induced B cell proliferation in vitro. Methods: Surface plasmon resonance imaging (SPRi) was used to screen the target protein of voacamine, while CCK-8 kit was used to evaluate cytotoxicity. Mitogen-induced proliferation assay was carried out to assess the inhibitory effect of voacamine on Con A-induced T cell proliferation and LPSinduced B cell proliferation. The binding characteristics of voacamine were investigated using a binding model with IL-2Rα constructed based on molecular docking simulation. Results: Voacamine had a high-affinity for IL-2Rα with an equilibrium dissociation constant (KD) of 1.85×10-8 M. Cytotoxicity data showed that voacamine did not exhibit cytotoxicity at concentrations lower than 0.32 µM. However, it exerted significant immunosuppressive effect on B cells at a lower concentration, but had no influence on proliferation of T cells. Autodock results indicate that voacamine has a good interaction with the enzyme active site. Conclusion: Voacamine and its analogues exert influence on the immune system.

To improve the naringinase production of Aspergillus tubingensis UA13, shorten the fermentation period, and verify its industrial application value, naringinase production conditions were optimized, and 5 L scale-up study in stirred tank bioreactor was carried out. Parameters, including carbon, nitrogen sources and inducer, optimal seed age, inoculum amount, temperature and pH, were adjusted and optimized in shaking flask. Keeping pH at the optimal value 6 in bioreactor, dissolved oxygen was monitored during the fermentation and the optimal stirring rate was investigated. In 5 L scale-up study, the highest naringinase activity was 72.62 U/mL, which was 1.75 times higher than that (41.52 U/mL) in shaking flask and the fermentation period was shortened by 24 h.

Cytochrome b (Cytb) sequences from 23 specimens of Mastacembelus spp. from the Rokel River, Taia/Jong River basins, and Freetown Peninsula were used in this study. These sequences were used to perform a gene-based phylogenetic analysis along with closely allied congeneric species in the Upper Guinea Forest in Africa. The resulting phylogenies inferred from Cytb showed populations of M. liberiensis from the Rokel River basin clustered into an exclusive lineage being sister to the lineage formed by M. greshoffi from the Congo basin. The Freetown Peninsula population of M. liberiensis clustered with sequences previously identified as M. taiaensis from the Taia/Jong River basin, sister to sequences of M. taiaensis from the Rokel River basin. The paired lineages were sister to the lineage formed by sequences from samples of the Taia/Jong River basin. These findings lead to the following conclusions: (1) hidden species diversity of spiny eels exists in either the Rokel River or the Jong River basin; (2) a likely available name for this species from the Freetown Peninsula is M. laticauda distinct from M. liberiensis; (3) given the diversity within M. liberiensis observed in the rivers sampled in Sierra Leone, it seems likely that the remaining rivers of Liberia and Sierra Leone reported having M. liberiensis may also harbor undescribed diversity. It is difficult to elevate some available junior synonyms based solely on a phylogeny inferred from Cytochrome b. We suggest that more samples from the entire range of M. liberiensis are needed and an integrated approach is required.

A lack of an updated checklist of freshwater fish species from Lake Dongting is a great hindrance to further biodiversity analysis. A seasonal survey of fishes in the lake was conducted from October 2017 to January 2019. Based on the data obtained during the field survey and coupled with known literature and the latest taxonomic development of relevant taxa, the species checklist of fishes from Lake Dongting was updated. A total of 130 species from 12 orders, 30 families and 76 genera has been documented, containing 126 native species and four alien species. Its fish fauna is dominated by the Xenocyprididae that has the highest number of included species (30), followed by the Gobionidae (25) and Acheilognathidae (11). This checklist comprises 20 species undergoing nomenclatural changes and 11 new records, eight of which are native and three exotic. It excludes 20 species, which have been reported in error in historical works, due to synonyms, erroneous records, taxonomic changes and unconfirmed records. Unsampled in this survey were 34 species that are ecologically specialised: migratory, rheophilic, predatory, shellfish-dependent or pelagic-egg-spawning. While some of these species eluded capture likely due to the paucity of population, others may have been extirpated in Lake Dongting perhaps owing to human perturbations, such as river damming across affluents or the Chang-Jiang mainstem, sand dredging, overfishing or water pollution. The updated checklist lays a sound foundation for biodiversity conservation of fishes in Lake Dongting.

Background Developmental signaling pathways such as those of Hedgehog (HH) and WNT play critical roles in cancer stem cell self-renewal, migration, and differentiation. They are often constitutively activated in many human malignancies, including non-small cell lung cancer (NSCLC). Previously, we reported that two oxysterol derivatives, Oxy186 and Oxy210, are potent inhibitors of HH/GLI signaling and NSCLC cancer cell growth. In addition, we also showed that Oxy210 is a potent inhibitor of TGF-β/SMAD signaling. In this follow-up study, we further explore the mechanism of action by which these oxysterols control NSCLC cell proliferation and tumor growth. Results Using a GLI-responsive luciferase reporter assay, we show here that HH ligand could not mount a signaling response in the NSCLC cell line A549, even though Oxy186 and Oxy210 still inhibited non-canonical GLI activity and suppressed the proliferation of A549 cells. Further, we uncover an unexpected activity of these two oxysterols in inhibiting the WNT/β-catenin signaling at the level of LRP5/6 membrane receptors. We also show that in a subcutaneous xenograft tumor model generated from A549 cells, Oxy186, but not Oxy210, exhibits strong inhibition of tumor growth. Subsequent RNA-seq analysis of the xenograft tumor tissue reveal that the WNT/β-catenin pathway is the target of Oxy186 in vivo. Conclusion The oxysterols Oxy186 and Oxy210 both possess inhibitory activity towards WNT/β-catenin signaling, and Oxy186 is also a potent inhibitor of NSCLC tumor growth.

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.

The occurrence of portal vein tumor thrombus (PVTT) is strongly correlated to the staging and poor prognosis of hepatocellular carcinoma (HCC) patients. However, the mechanisms of PVTT formation remain unclear. This study aimed to investigate differentially expressed genes (DEGs) between primary tumor (PT) and PVTT tissues and comprehensively explored the underlying mechanisms of PVTT formation. The DEGs between PT and paired PVTT tissues were analyzed using transcriptional data from the Gene Expression Omnibus (GEO) database. The expression, clinical relevance, prognostic significance, genetic alternations, DNA methylation, correlations with immune infiltration, co-expression correlations, and functional enrichment analysis of the DEGs were explored using multiple databases. As result, 12 DEGs were commonly down-expressed in PVTT compared with PT tissues among three datasets. The expression of DCN, CCL21, IGJ, CXCL14, FCN3, LAMA2, and NPY1R was progressively decreased from normal liver, PT, to PVTT tissues, whose up-expression associated with favorable survivals of HCC patients. The genetic alternations and DNA methylation of the DEGs frequently occurred, and several methylated CpG sites of the DEGs significantly correlated with outcomes of HCC patients. The immune infiltration in the tumor microenvironment of HCC was correlated with the expression level of the DEGs. Besides, the DEGs and their co-expressive genes participated in the biological processes of extracellular matrix (ECM) organization and focal adhesion. In summary, this study indicated the dysregulation of ECM and focal adhesion might contribute to the formation of PVTT. And the above seven genes might serve as potential biomarkers of PVTT occurrence and prognosis of HCC patients.

This work investigates a robust container vessel sequencing (RCVS) problem in a service route. As weekly demands vary dramatically and cannot be forecasted accurately, shipping companies need to de...

We find that, at the daily level, none of the VIX futures Exchange-Traded Products (ETPs) track their intrinsic values perfectly, although the tracking improves at the weekly and monthly frequency. We show that all products tracking deviations are driven by mainly driven by limits to arbitrage, measured by market conditions, liquidity and transaction costs. Exchange-Traded Funds’ (ETFs’) deviations are more significantly related to fund flows, which shows authorized participants taking advantage of arbitrage opportunities by creating/redeeming ETF units. The Exchange-Traded Notes (ETNs) do not have this mechanism, creation and redemption is reliant on the issuers and delayed, so their deviations are less related to flows.

Within the eastern portion of the Carletonville gold field, the gold- and uranium-rich Carbon Leader reef of the Central Rand Group (Witwatersrand Supergroup) is truncated by an erosion channel. This channel is asymmetrical and lenticular in shape, measuring 150 to 180 m in width and up to 100 m in depth. High-resolution seismic data show that the erosion channel cuts from the Carbon Leader reef into all older units of the Central Rand Group down to the Roodepoort Formation of the underlying West Rand Group. A total of seven boreholes were drilled into the channel, revealing that it is composed of quartzite at its base (9 m thick), overlain by deformed (lower) and laminated (upper) chloritoid-bearing shale (21 m thick) and quartzite (18 m thick). The Carbon Leader reef is highly enriched in gold (5–40 g/t Au), whereas the gold tenor of the erosion channel fill is in general much lower (

We demonstrate that integrating 3D reflection seismics with machine learning (ML) can bring many benefits for the future development of the mining industry. We use a serial integration of reflection seismics, which identifies economic horizon-depression structures known as potholes within the western Bushveld Complex. Thereafter, agglomerative clustering is applied to the resulting data, using features engineered from the physical characteristics of the potholes. Our results indicate that potholes can be divided into several classes based on characteristic features; e.g., large potholes are substantially less steep than small potholes. Furthermore, we model this empirical relationship and show that it can be used to predict average sizes of potholes given their typical in-mine exposures. We also demonstrate that pothole formation is likely to have been initiated depth-wise, followed by lateral increases in size. Lastly, we demonstrate that our serial application of seismically based data generation and ML-based data analytics is a viable alternative to conventional geostastistical analysis, especially for the classification, prediction, and modeling of geologic structures such as potholes.

In protostellar cores, sulfur species are effective probes for the energetic environments, such as shocked regions. With the majority of sulfur depleted on dust grains, sulfur-bearing molecules could be liberated back to gas phase by shocks associated with accretion and outflow activities. Therefore, the gas-phase abundance of these molecules may be correlated to the change of dust properties, which can be investigated through polarization observations. Here we present a comparison study of sulfur species and dust polarization at ∼100 au scale for nine protostars in the Perseus Molecular Cloud. Overall, the emission of sulfur-bearing molecules correlates with the high and disordered polarization in the extended continuum of eight sources, indicating intense physical conditions (e.g., high temperature) and/or change of dust properties within these regions, while no clear correlation is seen for Per-emb-14. For the more evolved sources with clear disk structures (Per-emb-50 and −18), the enhanced SO/SO2 emission overlaps with the stark contrast of polarization in the shocked regions near the centrifugal barriers. In the six sources with more extended CS and SO emission, such as Per-emb-11 and -5, the polarization enhancement correlates with the outer edge of outflow cavities and other filaments probed by sulfur-bearing molecules, revealing soft shocks along the outflows and envelopes. Such comparison studies could provide additional diagnostics of the physical properties and activities in star-forming processes, especially for the shocked regions.

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.

This is the first paper to study the options written on the Invesco Currency Shares Australian Dollar Trust (FXA) exchange‐traded fund (ETF). We quantify the empirical characteristics of the FXA option implied volatility (IV) curve showing that it exhibits a smirk shape, as in US equity options, and the curves become more negatively sloped and exhibit more convexity as the time to maturity increases. During the Global Financial Crisis (GFC) period and a bullish period, IV dramatically increased and the slope became even steeper across all maturities indicating that downside insurance is relatively expensive. Further, the information in the quantified IV curve factors has some predictive power for monthly FXA returns.

We provide a comprehensive study of the implied volatility (IV) smirk in the SPDR S&P 500 Exchange-Traded Fund (SPY ETF) option market. In general, the IV curves are downward sloping with little cu...