We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Multimorbidity, especially physical–mental multimorbidity, is an emerging global health challenge. However, the characteristics and patterns of physical–mental multimorbidity based on the diagnosis of mental disorders in Chinese adults remain unclear.
Methods
A cross-sectional study was conducted from November 2004 to April 2005 among 13,358 adults (ages 18–65years) residing in Liaoning Province, China, to evaluate the occurrence of physical–mental multimorbidity. Mental disorders were assessed using the Composite International Diagnostic Interview (version 1.0) with reference to the Diagnostic and Statistical Manual of Mental Disorders (3rd Edition Revised), while physical diseases were self-reported. Physical–mental multimorbidity was assessed based on a list of 16 physical and mental morbidities with prevalence ≥1% and was defined as the presence of one mental disorder and one physical disease. The chi-square test was used to calculate differences in the prevalence and comorbidity of different diseases between the sexes. A matrix heat map was generated of the absolute number of comorbidities for each disease. To identify complex associations and potential disease clustering patterns, a network analysis was performed, constructing a network to explore the relationships within and between various mental disorders and physical diseases.
Results
Physical–mental multimorbidity was confirmed in 3.7% (498) of the participants, with a higher prevalence among women (4.2%, 282) than men (3.3%, 216). The top three diseases with the highest comorbidity rate and average number of comorbidities were dysphoric mood (86.3%; 2.86), social anxiety disorder (77.8%; 2.78) and major depressive disorder (77.1%; 2.53). A physical–mental multimorbidity network was visually divided into mental and physical domains. Additionally, four distinct multimorbidity patterns were identified: ‘Affective-addiction’, ‘Anxiety’, ‘Cardiometabolic’ and ‘Gastro-musculoskeletal-respiratory’, with the digestive-respiratory-musculoskeletal pattern being the most common among the total sample. The affective-addiction pattern was more prevalent in men and rural populations. The cardiometabolic pattern was more common in urban populations.
Conclusions
The physical–mental multimorbidity network structure and the four patterns identified in this study align with previous research, though we observed notable differences in the proportion of these patterns. These variations highlight the importance of tailored interventions that address specific multimorbidity patterns while maintaining broader applicability to diverse populations.
Recent studies have increasingly utilized gradient metrics to investigate the spatial transitions of brain organization, enabling the conversion of macroscale brain features into low-dimensional manifold representations. However, it remains unclear whether alterations exist in the cortical morphometric similarity (MS) network gradient in patients with schizophrenia (SCZ). This study aims to examine potential differences in the principal MS gradient between individuals with SCZ and healthy controls and to explore how these differences relate to transcriptional profiles and clinical phenomenology.
Methods
MS network was constructed in this study, and its gradient of the network was computed in 203 patients with SCZ and 201 healthy controls, who shared the same demographics in terms of age and gender. To examine irregularities in the MS network gradient, between-group comparisons were carried out, and partial least squares regression analysis was used to study the relationships between the MS network gradient-based variations in SCZ, and gene expression patterns and clinical phenotype.
Results
In contrast to healthy controls, the principal MS gradient of patients with SCZ was primarily significantly lower in sensorimotor areas, and higher in more areas. In addition, the aberrant gradient pattern was spatially linked with the genes enriched for neurobiologically significant pathways and preferential expression in various brain regions and cortical layers. Furthermore, there were strong positive connections between the principal MS gradient and the symptomatologic score in SCZ.
Conclusions
These findings showed changes in the principal MS network gradient in SCZ and offered potential molecular explanations for the structural changes underpinning SCZ.
This case study provides a comprehensive analysis of the intricate political risks faced by TikTok, the Chinese social media giant, within the complex US political landscape. Beginning with an exploration of the security concerns articulated by the US government, the discussion centers on TikTok’s data collection practices and their perceived impact on US national security. The narrative unfolds by elucidating the multifaceted strategies employed by TikTok and its parent company, ByteDance, to address these challenges, including litigation, endeavors toward Americanization, and technological adaptations. It also examines the evolution in the US government’s stance as well as TikTok’s adaptive strategies aimed at sustaining and expanding its presence in the US market. The study depicts the responses of the Chinese government to US policies, unraveling the broader implications of these developments on the global political-economic landscape, exploring the dynamics involved in US-China relations, and providing a deeper understanding of the complexities inherent in such interactions. Finally, this case study invites readers to engage in contemplation on the broader themes of political risks faced by multinational corporations, the challenges inherent in navigating global legal frontiers, and the intricate nature of US-China relations.
Major depressive disorder (MDD) is a heterogeneous condition characterized by significant intersubject variability in clinical presentations. Recent neuroimaging studies have indicated that MDD involves altered brain connectivity across widespread regions. However, the variability in abnormal connectivity among MDD patients remains understudied.
Methods
Utilizing a large, multi-site dataset comprising 1,276 patients with MDD and 1,104 matched healthy controls, this study aimed to investigate the intersubject variability of structural covariance (IVSC) and functional connectivity (IVFC) in MDD.
Results
Patients with MDD demonstrated higher IVSC in the precuneus and lingual gyrus, but lower IVSC in the medial frontal gyrus, calcarine, cuneus, and cerebellum anterior lobe. Conversely, they exhibited an overall increase in IVFC across almost the entire brain, including the middle frontal gyrus, anterior cingulate cortex, hippocampus, insula, striatum, and precuneus. Correlation and mediation analyses revealed that abnormal IVSC was positively correlated with gray matter atrophy and mediated the relationship between abnormal IVFC and gray matter atrophy. As the disease progressed, IVFC increased in the left striatum, insula, right lingual gyrus, posterior cingulate, and left calcarine. Pharmacotherapy significantly reduced IVFC in the right insula, superior temporal gyrus, and inferior parietal lobule. Furthermore, we found significant but distinct correlations between abnormal IVSC and IVFC and the distribution of neurotransmitter receptors, suggesting potential molecular underpinnings. Further analysis confirmed that abnormal patterns of IVSC and IVFC were reproducible and MDD specificity.
Conclusions
These results elucidate the heterogeneity of abnormal connectivity in MDD, underscoring the importance of addressing this heterogeneity in future research.
The previous study indicated that ubiquitination is involved in the freezing tolerance of hydrated seeds. Parthenolide (PN), inducing the ubiquitination of MDM2, an E3 ring-finger ubiquitin ligase, adversely affects the freezing tolerance of hydrated lettuce seeds. Therefore, a proteomics analysis was conducted to identify PN's targets in hydrated seeds exposed to cooling conditions. Several pathways, including oxidative phosphorylation (KEGG00190), amino sugar and nucleotide sugar metabolism (KEGG00520), and biosynthesis of nucleotide sugars (KEGG01250), were enriched in the PN treatment under slow-cooling conditions (3°C h−1, P < 0.05). Among the proteins in oxidative phosphorylation, the expression of NADH dehydrogenases and ATP synthases (ATPsyn) decreased in PN treatment. In contrast, uncoupling proteins increased after PN treatment, which led to the dissociation of the electron transport chain from ATP synthesis. Treatments with rotenone, dicoumarol, and oligomycin (i.e., oxidative phosphorylation inhibitors) decreased the survival rate of hydrated seeds under freezing conditions, which indicated that energy metabolism was related to the freezing tolerance of hydrated seeds. The predicted interactions between PN and MDM2-like proteins of Lactuca indicated that LsMDM2-5 forms two potential hydrogen bonds with PN. Furthermore, based on AlphaFold predictions and yeast 2-hybrid results, MDM2-5 might interact directly with NADH2. The knockdown of MDM2-5 by RNAi caused a higher level of NADH2 and ATPsyn and a higher freezing tolerance of hydrated seeds. This indicated that MDM2 played negative roles in regulating ATP synthesis and freezing tolerance of hydrated seeds.
The collapse of an initially spherical cavitation bubble near a free surface leads to the formation of two jets: a downward jet into the liquid, and an upward jet penetrating the free surface. In this study, we examine the surprising interaction of a bubble trapped in a stable cavitating vortex ring approaching a free surface. As a result, a single fast and tall liquid jet forms. We find that this jet is observed only above critical Froude numbers ($Fr$) and Weber numbers ($We$) when ${Fr}^2 (1.6-2.73/{We}) > 1$, illustrating the importance of inertia, gravity and surface tension in accelerating this novel jet and thereby reaching heights several hundred times the radius of the vortex ring. Our experimental results are supported by numerical simulations, revealing that the underlying mechanism driving the vortex ring acceleration is the disruption of the equilibrium of high-pressure regions at the front and rear of the vortex ring caused by the free surface. Quantitative analysis based on the energy relationships elucidates that the velocity ratio between the maximum velocity of the free-surface jet and the translational velocity of the vortex ring is relatively stable yet is attenuated by surface tension when the jet is mild.
Differential item functioning (DIF) analysis is an important step in establishing the validity of measurements. Most traditional methods for DIF analysis use an item-by-item strategy via anchor items that are assumed DIF-free. If anchor items are flawed, these methods will yield misleading results due to biased scales. In this article, based on the fact that the item’s relative change of difficulty difference (RCD) does not depend on the mean ability of individual groups, a new DIF detection method (RCD-DIF) is proposed by comparing the observed differences against those with simulated data that are known DIF-free. The RCD-DIF method consists of a D-QQ (quantile quantile) plot that permits the identification of internal references points (similar to anchor items), a RCD-QQ plot that facilitates visual examination of DIF, and a RCD graphical test that synchronizes DIF analysis at the test level with that at the item level via confidence intervals on individual items. The RCD procedure visually reveals the overall pattern of DIF in the test and the size of DIF for each item and is expected to work properly even when the majority of the items possess DIF and the DIF pattern is unbalanced. Results of two simulation studies indicate that the RCD graphical test has Type I error rate comparable to those of existing methods but with greater power.
In educational and psychological measurement when short test forms are used, the asymptotic normality of the maximum likelihood estimator of the person parameter of item response models does not hold. As a result, hypothesis tests or confidence intervals of the person parameter based on the normal distribution are likely to be problematic. Inferences based on the exact distribution, on the other hand, do not suffer from this limitation. However, the computation involved for the exact distribution approach is often prohibitively expensive. In this paper, we propose a general framework for constructing hypothesis tests and confidence intervals for IRT models within the exponential family based on exact distribution. In addition, an efficient branch and bound algorithm for calculating the exact p value is introduced. The type-I error rate and statistical power of the proposed exact test as well as the coverage rate and the lengths of the associated confidence interval are examined through a simulation. We also demonstrate its practical use by analyzing three real data sets.
The estimation of workspace for parallel kinematic machines (PKMs) typically relies on geometric considerations, which is suitable for PKMs operating under light load conditions. However, when subjected to heavy load, PKMs may experience significant deformation in certain postures, potentially compromising their stiffness. Additionally, heavy load conditions can impact motor loading performance, leading to inadequate motor loading in specific postures. Consequently, in addition to geometric constraints, the workspace of PKMs under heavy load is also constrained by mechanism deformation and motor loading performance.
This paper aims at developing a new heavy load 6-PSS PKM for multi-degree of freedom forming process. Additionally, it proposes a new method for estimating the workspace, which takes into account both mechanism deformation and motor loading performance. Initially, the geometric workspace of the machine is predicted based on its geometric configuration. Subsequently, the workspace is predicted while considering the effects of mechanism deformation and motor loading performance separately. Finally, the workspace is synthesized by simultaneously accounting for both mechanism deformation and motor loading performance, and a new index of workspace utilization rate is proposed. The results indicate that the synthesized workspace of the machine diminishes as the load magnitude and load arm increase. Specifically, under a heavy load magnitude of 6000 kN and a load arm of 200 mm, the utilization rate of the synthesized workspace is only 9.9% of the geometric workspace.
In this study, nine isonitrogenous experimental diets containing graded levels of carbohydrates (40 g/kg, 80 g/kg and 120 g/kg) and crude lipids (80 g/kg, 120 g/kg and 160 g/kg) were formulated in a two-factor (3 × 3) orthogonal design. A total of 945 mandarin fish with similar body weights were randomly assigned to twenty-seven tanks, and the experiment diets were fed to triplicate tanks twice daily for 10 weeks. Results showed that different dietary treatments did not significantly affect the survival rate and growth performance of mandarin fish. However, high dietary lipid and carbohydrate levels significantly decreased the protein content of the whole body and muscle of cultured fish. The lipid content of the whole body, liver and muscle all significantly increased with increasing levels of dietary lipid, while only liver lipid level was significantly affected by dietary carbohydrate level. Hepatic glycogen content increased significantly with increasing dietary carbohydrate levels. As to liver antioxidant capacity, malondialdehyde content increased significantly with increasing dietary lipid or carbohydrate content, and catalase activity showed an opposite trend. Superoxide dismutase activity increased significantly with increasing levels of dietary lipid but decreased first and then increased with increasing dietary carbohydrate levels. Additionally, the increase in both dietary lipid and carbohydrate levels resulted in a significant reduction in muscle hardness. Muscle chewiness, gumminess and shear force were only affected by dietary lipid levels and decreased significantly with increasing dietary lipid levels. In conclusion, considering all the results, the appropriate dietary lipids and carbohydrate levels for mandarin fish were 120 g/kg and 80 g/kg, respectively.
We present a theory that quantifies the interplay between intrapore and interpore flow variabilities and their impact on hydrodynamic dispersion. The theory reveals that porous media with varying levels of structural disorder exhibit notable differences in interpore flow variability, characterised by the flux-weighted probability density function (PDF), $\hat {\psi }_\tau (\tau ) \sim \tau ^{-\theta -2}$, for advection times $\tau$ through conduits. These differences result in varying relative strengths of interpore and intrapore flow variabilities, leading to distinct scaling behaviours of the hydrodynamic dispersion coefficient $D_L$, normalised by the molecular diffusion coefficient $D_m$, with respect to the Péclet number $Pe$. Specifically, when $\hat {\psi }_\tau (\tau )$ exhibits a broad distribution of $\tau$ with $\theta$ in the range of $(0, 1)$, the dispersion undergoes a transition from power-law scaling, $D_L/D_m \sim Pe^{2-\theta }$, to linear scaling, $D_L/D_m \sim Pe$, and eventually to logarithmic scaling, $D_L/D_m \sim Pe\ln (Pe)$, as $Pe$ increases. Conversely, when $\tau$ is narrowly distributed or when $\theta$ exceeds 1, dispersion consistently follows a logarithmic scaling, $D_L/D_m \sim Pe\ln (Pe)$. The power-law and linear scaling occur when interpore variability predominates over intrapore variability, while logarithmic scaling arises under the opposite condition. These theoretical predictions are supported by experimental data and network simulations across a broad spectrum of porous media.
This study aimed to demonstrate the utilization value of 1PN embryos. The 1PN zygotes collected from December 2021 to September 2022 were included in this study. The embryo development, the pronuclear characteristics, and the genetic constitutions were investigated. The overall blastocyst formation and good-quality blastocyst rates in 1PN zygotes were 22.94 and 16.24%, significantly lower than those of 2PN zygotes (63.25 and 50.23%, respectively, P = 0.000). The pronuclear characteristics were found to be correlated with the developmental potential. When comparing 1PN zygotes that developed into blastocysts to those that arrested, the former exhibited a significantly larger area (749.49 ± 142.77 vs. 634.00 ± 119.05, P = 0.000), a longer diameter of pronuclear (29.81 ± 3.08 vs. 27.30 ± 3.00, P = 0.000), and a greater number of nucleolar precursor body (NPB) (11.56 ± 3.84 vs. 7.19 ± 2.73, P = 0.000). Among the tested embryos, the diploidy euploidy rate was significantly higher in blastocysts in comparison with the arrested embryos (66.67 vs. 11.76%, P = 0.000), which was also significantly higher in IVF-1PN blastocysts than in ICSI-1PN blastocysts (75.44 vs. 25.00%, P = 0.001). However, the pronuclear characteristics were not found to be linked to the chromosomal ploidy once they formed blastocysts.
In summary, while the developmental potential of 1PN zygotes is reduced, our study shows that, in addition to the reported pronuclear area and diameter, the number of NPB is also associated with their developmental potential. The 1PN blastocysts exhibit a high diploidy euploidy rate, are recommend to be clinically used post genetic testing, especially for patients who do not have other 2PN embryos available.
This study aimed to assess the relationship between COVID-19 infection-related conditions and depressive symptoms among medical staff after easing the zero-COVID policy in China, and to further examine the mediating role of professional burnout.
Methods
A total of 1716 medical staff from all levels of health care institutions in 16 administrative districts of Beijing, China, were recruited to participate at the end of 2022 in this cross-sectional study. Several multiple linear regressions and mediating effects tests were performed to analyze the data.
Results
At the beginning of the end of the zero-COVID policy in China, 91.84% of respondents reported infection with COVID-19. After adjusting for potential confounding variables, the severity of infection symptoms was significantly positively associated with high levels of depressive symptoms (β = 0.06, P < 0.001), and this association was partially mediated by professional burnout. Specifically, emotional exhaustion (95% CI, 0.131, 0.251) and depersonalization (95% CI, 0.009, 0.043) significantly mediated the association between the severity of infection symptoms and depressive symptoms.
Conclusions
The mental health of medical staff with more severe symptoms of COVID-19 infection should be closely monitored. Also, interventions aimed at reducing emotional exhaustion and depersonalization may effectively reduce their risk of developing depressive symptoms.
In contemporary neuroimaging studies, it has been observed that patients with major depressive disorder (MDD) exhibit aberrant spontaneous neural activity, commonly quantified through the amplitude of low-frequency fluctuations (ALFF). However, the substantial individual heterogeneity among patients poses a challenge to reaching a unified conclusion.
Methods
To address this variability, our study adopts a novel framework to parse individualized ALFF abnormalities. We hypothesize that individualized ALFF abnormalities can be portrayed as a unique linear combination of shared differential factors. Our study involved two large multi-center datasets, comprising 2424 patients with MDD and 2183 healthy controls. In patients, individualized ALFF abnormalities were derived through normative modeling and further deconstructed into differential factors using non-negative matrix factorization.
Results
Two positive and two negative factors were identified. These factors were closely linked to clinical characteristics and explained group-level ALFF abnormalities in the two datasets. Moreover, these factors exhibited distinct associations with the distribution of neurotransmitter receptors/transporters, transcriptional profiles of inflammation-related genes, and connectome-informed epicenters, underscoring their neurobiological relevance. Additionally, factor compositions facilitated the identification of four distinct depressive subtypes, each characterized by unique abnormal ALFF patterns and clinical features. Importantly, these findings were successfully replicated in another dataset with different acquisition equipment, protocols, preprocessing strategies, and medication statuses, validating their robustness and generalizability.
Conclusions
This research identifies shared differential factors underlying individual spontaneous neural activity abnormalities in MDD and contributes novel insights into the heterogeneity of spontaneous neural activity abnormalities in MDD.
This study aimed to investigate the effects of esketamine (Esk) combined with dexmedetomidine (Dex) on postoperative delirium (POD) and quality of recovery (QoR) in elderly patients undergoing thoracoscopic radical lung cancer surgery.
Methods
In this prospective, randomized, and controlled study, 172 elderly patients undergoing thoracoscopic radical lung cancer surgery were divided into two groups: the Esk + Dex group (n = 86) and the Dex group a (n = 86). The primary outcome was the incidence of POD within 7 days after surgery and the overall Quality of Recovery−15 (QoR − 15) scores within 3 days after surgery. Secondary outcomes included postoperative adverse reactions, extubation time, PACU stay, and hospitalization time. Serum levels of IL-6, IL-10, S100β protein, NSE, CD3+, CD4+, and CD8+ were detected from T0 to T5.
Results
Compared with the Dex group, the incidence of POD in the Esk + Dex group was significantly lower at 7 days after surgery (14.6% vs 30.9%; P = 0.013). The QoR − 15 score was significantly increased 3 days after surgery (P < 0.01). Levels of IL-6 and CD8+ were significantly decreased, and IL − 10 levels were significantly increased at T1-T2 (P < 0.05). At T1-T4, NSE levels were significantly decreased, while CD3+ and CD4+/CD8+ values were significantly increased (P < 0.01). At T1-T5, serum S100β protein concentration decreased significantly, and CD4+ value increased significantly (P < 0.01). The incidence of nausea/vomiting and hyperalgesia decreased significantly 48 hours after surgery (P < 0.01). The duration of extubation, PACU stay, and postoperative hospitalization were significantly shortened.
Conclusions
Esketamine combined with dexmedetomidine can significantly reduce the POD incidence and improve the QoR in patients undergoing thoracoscopic radical lung cancer surgery, which may be related to the improvement of cellular immune function.
Australian Banking and Finance Law and Regulation provides a comprehensive, up-to-date and accessible introduction to the complexities of contemporary law and regulation of banking and financial sectors in one volume. The book provides a detailed analysis of Australia's financial market regulatory framework and the theoretical underpinnings of government intervention in the field. It delves into the legal changes implemented in response to the Global Financial Crisis and recent local scandals, exploring the complexities and subtleties of the 'banker–customer' relationship. Readers will appreciate the clear and concise treatment of key issues, cases and examples that offer an overview of major developments. The questions and answers at the end of each chapter serve as an effective tool for readers to assess and reinforce their grasp of the fundamental principles discussed.
The liver has multiple functions such as detoxification, metabolism, synthesis and storage. Folate is a water-soluble vitamin B9, which participates in one-carbon transfer reactions, maintains methylation capacity and improves oxidative stress. Folic acid is a synthetic form commonly used as a dietary supplement. The liver is the main organ for storing and metabolising folate/folic acid, and the role of folate/folic acid in liver diseases has been widely studied. Deficiency of folate results in methylation capacity dysfunction and can induce liver disorders. However, adverse effects of excessive use of folic acid on the liver have also been reported. This review aims to explore the mechanism of folate/folic acid in different liver diseases, promote further research on folate/folic acid and contribute to its rational clinical application.
Paranosema locustae is an environmentally friendly parasitic predator with promising applications in locust control. In this study, transcriptome sequencing was conducted on gonadal tissues of Locusta migratoria males and females infected and uninfected with P. locustae at different developmental stages. A total of 18,635 differentially expressed genes (DEGs) were identified in female ovary tissue transcriptomes, with the highest number of DEGs observed at 1 day post-eclosion (7141). In male testis tissue transcriptomes, a total of 32,954 DEGs were identified, with the highest number observed at 9 days post-eclosion (11,245). Venn analysis revealed 25 common DEGs among female groups and 205 common DEGs among male groups. Gene ontology and Kyoto Encyclopaedia of Genes and Genome analyses indicated that DEGs were mainly enriched in basic metabolism such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, and immune response processes. Protein–protein interaction analysis results indicated that L. migratoria regulates the expression of immune- and reproductive-related genes to meet the body's demands in different developmental stages after P. locustae infection. Immune- and reproductive-related genes in L. migratoria gonadal tissue were screened based on database annotation information and relevant literature. Genes such as Tsf, Hex1, Apolp-III, Serpin, Defense, Hsp70, Hsp90, JHBP, JHE, JHEH1, JHAMT, and VgR play important roles in the balance between immune response and reproduction in gonadal tissues. For transcriptome validation, Tsf, Hex1, and ApoLp-III were selected and verified by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation analysis revealed that the qRT-PCR expression patterns were consistent with the RNA-Seq results. These findings contribute to further understanding the interaction mechanisms between locusts and P. locustae.
In Australia, the regulatory oversight of credit and financial products is primarily vested at the federal level. Credit products are regulated by the National Consumer Credit Protection Act 2009 (Cth). This Act replaced the prior state-based system, notably the Uniform Consumer Credit Code. This chapter expounds upon the regulatory architecture governing financial products. It is paramount to acknowledge that additional regulations, regulatory guides and sector-specific codes are crucial to the Australian regulatory matrix concerning financial affairs. Before embarking on a detailed analysis, a brief overview of the historical context leading to the present regulatory system for financial products in Australia is warranted. Pivotal moments in this narrative are the Wallis Inquiry, the Murray Inquiry and the Banking Royal Commission, which largely shaped financial regulation as it is today. With this foundational understanding established, our subsequent focus transitions to the requisite licensing conditions and the salient duties incumbent upon licensees. The most recently introduced product design and distribution obligations and product intervention order are also discussed.