This work is focused on the study of the generalized forms of the fractional derivatives of Reimann-Liouville, Caputo and Hilfer, in terms of Ψ functions. The fractional derivatives of Ψ-Prabhakar, Ψ-Hilfer-Prabhakar, and its regularized form are also described in terms of Ψ-Mittage-Leffler type functions. These are then used to solve a number of Cauchy type equations involving Ψ-Hilfer-Prabhakar fractional derivatives and their regularized form, including the generalized fractional free electron laser equation.

Solid Pseudopapilary Neoplasm (SPN) are rare tumors usually appearing in young females. Presentations beyond 40 are rare. We describe the case of a 52 years old patient with persistent abdominal pain diagnosed with an SPN of the uncinated pancreatic process. The diagnostic between SPN and neuroendocrine tumor (NET) was challenging.

The field of pharmacometrics has been responsible for countless advancements within the drug development space. In recent years, we have witnessed the implementation of both new and revived analytical methods to increase clinical trial success and even supplement the need for clinical trials all together. Throughout this article we will explore the path of pharmacometrics from its inception to present day. At this point in time, the target of drug development has been the average patient, and population approaches have primarily been utilized to support just that. The challenge we are now facing involves the translation from treating the typical patient to treating the real-world patient. For this reason, it is our opinion that future development efforts should account more for the individual. With advanced pharmacometric methods and growing technological infrastructure, precision medicine can become a development priority rather than a clinician's burden.

Biosafe wearable healthcare monitor has attracted significant attention owing to their applicability to wearable electronics. However, the narrow sensing range and poor response limit the application of flexible devices for comprehensive monitoring of human health-related physiological signals (i.e. pulse diagnosis). Critical challenges remain in the development of biocompatible materials and the design of flexible bio-integrated platforms for these purposes, targeting performance approaching those of conventional wafer-based technologies and long-term operational stability. In this context, this work presents a robust and flexible MXene/polydopamine (PDA)-composite-film-based pressure sensor in a portable/wearable fashion, which establishes a unique intercalated spherical-like PDA molecules structure, thereby resulting in excellent sensing performance. The MXene/PDA-based pressure sensor has sensitivity of up to 138.8 kPa-1 in the pressure range of 0.18-6.20 kPa with fast response and recovery speed (t1<100 ms; t2<50 ms). Associated embodiment involves real-time precise measurements of a variety of health-related physiological signals, ranging from wrist pulse, to finger motions, to vocalization and to facial expressions, with high sensitivity and accuracy. Studies on human subjects establish the clinical significance of these devices for future opportunities of health monitoring and intelligent control to predict and diagnose diseases.

This study compares longitudinal changes in the scales and characteristics of the ‘not out of my pocket’ (NOOMP) phenomenon, a welfare attitude in South Korea that supports expanding the welfare system but rejects tax increases. Using the Welfare Perception and Attitude Surveys, this study examines shifts in the scales and characteristics of NOOMP for major welfare policies. The results show that NOOMP is being alleviated; alleviation is largest for pensions, followed by public assistance, health insurance, and employment policies. These changes suggest that, to mitigate NOOMP, the welfare system should strengthen the benefit levels of health insurance, improve the gender inequality inherent in the national pension, build a social consensus on increases in public assistance, and expand employment insurance benefits to youth and the elderly.

The effect of wall material thermal conductivity on butane flame stability is investigated for microscale gas fired burners. The present study aims to provide a fundamental understanding of the butane flame stability of microscale gas fired burners at different wall material thermal conductivities. Particular emphasis is placed upon the stability limits over a range of equivalence ratios and the effect of wall material thermal conductivity on the butane flame stability. The results indicate that the wall material thermal conductivity is vital in determining the butane flame stability of the gas fired burners, as the walls are responsible for the majority of the upstream heat transfer as well as the external heat losses. The most effective way of increasing the lean stability limits of the burner is an increase in primary stream inlet temperature. Completing the combustion process near homogeneous stoichiometric conditions, by intensifying the mixing process, may increase nitrogen oxides emissions. To ensure that the combustion process of the furnace is not adversely affected by the presence of the device, the device should not adversely interfere with the flow of products of combustion away from the combustion zone for each burner. Low wall thermal conductivities result in large axial wall-temperature gradients and high maximum temperatures. High wall thermal conductivity leads to uniform temperature profiles without hotspots. Low wall thermal conductivities cause the flame to shift downstream. Increasing wall thermal conductivity has little effect on flame location unless there are significant external heat losses. Typical ceramics allow maximum external heat loss coefficients. Materials with lower wall thermal conductivities limit the upstream heat transfer. Materials with higher wall thermal conductivities result in enhanced heat transfer to the surroundings. The inlet flow velocity plays a competing role in flame stability. There is only a relatively narrow envelope of flow rates within which combustion can be stabilized. The maximum fluid temperature exceeds the adiabatic flame temperature of butane-air mixture computed for room temperature. Keywords: Burners; Combustion; Emissions; Extinction; Flames; Stability

An important objective of evolutionary biology has always been to grasp the evolutionary and genetic processes that contribute to speciation. The present work provides the first detailed account of the genetic and physiological adaptation to changing environmental temperatures as well as the reasons causing intraspecific divergence in the Eothenomys miletus from the Hengduan mountain (HM) region, one of the biodiversity hotspots. 161 E. miletus individuals from five populations in the HM region had their genomes simplified sequenced, and one additional individual from each community had their genomes resequenced. We then characterized the genetic diversity and population structure of each population and compared the phenotypic divergence in traits using neutral molecular markers. We detected significant phenotypic and genetic alterations in E. miletus from the HM region that were related to naturally occurring diverse habitats by combining morphometrics and genomic techniques. The E. miletus existed asymmetric gene flow patterns, indicating that five E. miletus populations exhibit a isolation-by-island model, and this was supported by the correlation between FST and geographic distance. Finally, PST estimated by phenotypic measures of most wild traits were higher than differentiation at neutral molecular markers, indicating directional natural selection favouring different phenotypes in different populations must have been involved to achieve this much differentiation. Our findings give information on the demographic history of E. miletus, new insights into their evolution and adaptability, and literature for studies of a similar nature on other wild small mammals from the HM region.

Recent declines in eastern wild turkeys (Meleagris gallopavo silvestris) has prompted increased interest in management and research of this important game species. However, the mechanisms underlying these declines are unclear, leaving uncertainty in how best to manage this species. Foundational to effective management of wildlife species is understanding the biotic and abiotic factors that influence demographic parameters and the contribution of vital rates to population growth. Our objectives for this study were to: 1) conduct a literature review to collect all published vital rates for eastern wild turkey over the last 50 years, 2) perform a scoping review of the biotic and abiotic factors that have been studied relative to wild turkey vital rates and highlight areas that require additional research, and 3) use the published vital rates to populate a life-stage simulation analysis (LSA) and identify the vital rates that make the greatest contribution to population growth. Based on published vital rates for eastern wild turkey, we estimated a mean asymptotic population growth rate (λ) of 0.91 (95% CI = 0.71, 1.12). Vital rates associated with after second year (ASY) females were most influential in determining population growth. Survival of ASY females had the greatest elasticity (0.53), while reproduction of ASY females had lower elasticity (0.21), but high process variance, causing it to explain a greater proportion of variance in λ. Our scoping review found that most research has focused on the effects of habitat characteristics at nest sites and the direct effects of harvest on adult survival, while research on topics such as disease, weather, predators, or anthropogenic activity on vital rates have received less attention. We recommend that future research take a more mechanistic approach to understanding variation in wild turkey vital rates as this will assist managers in determining the most appropriate management approach.

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Laboratory studies show detrimental effects of metal pollutants on invertebrate behaviour and cognition, even at low levels. Here, we report a field study of Western honey bees sampled from an historic mining site heavily contaminated with metal and metalloid pollution, particularly arsenic. We analysed more than 1,000 bees from five apiaries within 11 km of the world's largest gold mine in Southern France. Bees collected close to the mine exhibited decreased olfactory learning and memory performances and developed smaller heads. Three-dimensional scans of bee brains showed that the olfactory centres of bees sampled close to the mine were also smaller, indicating impairment of brain. Our study raises serious concerns about the health of honey bee populations in metal-polluted areas and illustrates how standard cognitive tests can be used for risk assessment.

The current understanding of multi-stress interplay assumes stresses occur in perfect synchrony, but this assumption is rarely met in the natural marine ecosystem. To understand the interplay between non-perfectly overlapped stresses in the ocean, we manipulated different temporal scenarios of acidification and assessed their effect on mercury toxicity in a marine copepod. We found that the scenario of past acidification aggravated mercury toxicity, but personal and persistent acidification mitigated the toxicity. This is because personal and persistent acidification initiated the energy compensation to enhance growth and mercury efflux. To explore how general temporal scenarios of acidification affected multi-stress interplay, we conducted a meta-analysis on marine animals and found that scenarios significantly changed the toxicity of several other metals. Our study thus demonstrates that time and duration of stresses modulate multi-stress interplay in the marine ecosystem, and suggests that future studies should move beyond the scenario of perfect synchrony.

It is well known that long time coherent integration (LTCI) can effectively improve the radar detection ability of manoeuvring weak targets, since a considerable signal-to-noise ratio (SNR) improvement can be achieved [1]. However, for most existing LTCI algorithms [2-5], there is a common assumption that the observed target is of the single motion stage (i.e., the motion parameters of targets are uniform) during the coherent processing interval (CPI). However, with the advancement of manoeuvrability and the increasement of CPI, the observed target might be of multiple motion stages. In this case, the above-mentioned LTCI algorithms will not be effective any more. The specific LTCI algorithms developed for manoeuvring weak target with multiple motion stages are relatively few. In [6], a short-time generalized radon-Fourier transform (STGRFT) based LTCI algorithm is proposed to remove range migration (RM) and Doppler frequency migration (DFM) effects and estimate the stage-changing point. Similar as GRFT[5], STGRFT can be able to obtain an excellent SNR gain through multi-dimension parametric searching. In [7], a reference signal is introduced to compensate the motion parameters change (MPC) effect between different motion stages, and then GRFT is utilized to achieve the coherent integration during the CPI. However, the computational load of these algorithms is quite high, since the key procedure is based on the multi-dimension parametric searching. This may deteriorate the engineering practicability of these algorithms.

Objective: To quantify the transplacental transmission of SARS-CoV-2 and antibodies in pregnant women and their new-borns according to the trimester of maternal infection. Design: This was a prospective observational multicentre study including pregnant women with positivity for SARS-CoV-2 by reverse transcription–polymerase chain reaction (RT‒PCR) or positivity by serology from April to December 2020. The study was designed to perform a systematic collection of mother/new-born dyad samples at birth. Setting: Eleven maternity wards in Eastern France Population: Pregnant women with confirmed COVID-19 infection during pregnancy and their new-borns. Methods: The SARS-CoV-2 viral load was measured by RT‒PCR. IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analysed according to the term of maternal infection. Main Outcome Measure: SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma and quantification of anti-SARS-CoV-2 antibody transfer. Results: Among 165 dyads enrolled, one congenital infection was confirmed (n=1 (0.63%) IC95% [0.02%; 3.48%]). Among 165 maternal sera tested, 107 (64.8%) were positive for IgG with a concentration > 25.6 BAU/ml. The average placental transfer ratio was 1.27 (95% CI [0.69–2.89]). The transfer ratio increased with increasing time between the onset of maternal infection and delivery (P value = 0.0001). Conclusions: We confirmed very low SARS-CoV-2 transplacental transmission of less than 1%. Transmission of antibodies is more likely when the infection occurs in the first or second trimester of pregnancy.

Dispersal, the movement of individuals away from their natal location to another location, is a basic driver of ecological and evolutionary processes. Direct measures of marine fish larval dispersal have shown that individual dispersal distances can vary over several orders of magnitude within a species. We currently do not know the causes of this variation. One plausible explanation for the cause of intraspecific variation in individual dispersal distances is dispersal plasticity. Dispersal plasticity, especially as an adaptive parental effect where parents can alter the dispersal phenotype of their offspring in response to an environmental cue, is widespread in terrestrial systems, but has yet to be described in marine fishes. In this study, we address a key, although often untested, condition for the evolution of dispersal plasticity as an adaptive parental effect: whether parents have information that would enable them to reliably predict the environmental conditions that their offspring will encounter. Using a wild population of orange anemonefish, Amphiprion percula, we investigate habitat quality predictability by testing for spatial autocorrelation in three habitat quality indicators: anemone size, female size, and egg clutch size. We found strong, positive spatial autocorrelation for all three habitat quality indicators from 50 to about 500 meters. This suggests that selection might favor parents that increase allocation to offspring that stay within 500 m if they are in good habitat and increase allocation to offspring that travel farther than this if they are in poor habitat. Results from this study lay solid foundations for further investigation of dispersal plasticity in A. percula and other marine fishes, providing testable hypotheses for probable causes of individual dispersal distance variation. Incorporating dispersal plasticity in our investigations of marine fish larval dispersal potentially could contribute to a greater understanding of marine fish metapopulation dynamics, and therefore fisheries recovery and reserve management.

Objective: This study estimated CMV molecular prevalence in placental biopsies as well as in umbilical blood cord and its correlation with infection of pregnant women and their newborns to determinate vertical transmission risks. Design: A cross-sectional study Setting: Obstetric Center of the University Hospital in Rio Grande, Brazil Population: 496 pregnant women and their newborns Methods: Biopsies were collected from peripheral and central portions of each placenta, separated on fetal and maternal interfaces, matched with cord blood, totaling 1488 samples. PCR technique and sequencing were used to investigate the prevalence. Main Outcome Measures: Bivariate and multivariate analysis were performed to determinate sociodemographic, clinical and gynecological data associated to CMV vertical transmission. Results: CMV DNA was found in 5.2% of placental maternal interface and 5.4% of fetal interface with a positive result for CMV in 3.6% in cord blood. In more than 90% of the cases, there was no match between positive CMV DNA cord blood and positive placentas, indicating vertical transmission ascending from genital tract. The income factor (less than 1 minimum wage) was significantly associated with prevalence of CMV in placentas (p = 0.03). In cord blood samples, non-white skin color and early age at the onset of sexual intercourse were risk factors associated with the infection (p = 0.04). Conclusions: The occurrence of CMV DNA found in cord blood suggests the pattern observed appears to be ascending from genital tract of asymptomatic mothers. Economical and environmental factors present a negative impact on fetal-maternal transmission of cytomegalovirus.

The stability of the ecosystem directly affects water quality and safety, fishery production, and people’s quality of life along the route. Therefore, a large amount of biological information on five dominant species of baitfish, including Hemiculter leucisculus, Acheilognathus macropterus, Rhodeus sericeus, Pseudorasbora parva, and Squalidus argentatus, was collected in the lower reaches of the Songhua River. The population parameters and variation rules of these fish were evaluated. The results showed that current exploitation of fish resources in the lower reaches of the Songhua River is excessive. The growth rate of baitfish is accelerating, but their growth potential is decreasing; the fish community structure is homogeneous, and the excessively small size of fish at a low age is obvious. In addition, the growth length coefficients of the five baitfish species were all greater than 0.2, which indicates fast growth; the growth performance indices were from 3.49 to 4.37. The exploitation rate of the Hemiculter leucisculus and Squalidus argentatus minnows was greater than 0.5, and the exploitation rates of all species except Pseudorasbora parva were higher than Emax. To ensure the size of the main baitfish populations in the lower reaches of the Songhua River, the mesh size of all nets should be controlled above 45 mm. In summary, these results provide a scientific basis for understanding the trend and growth of baitfish resources, identifying the distribution of major commercial or endangered fish feeding grounds in the region, and balancing ecosystem health integrity in the lower reaches of the Songhua River.

The future of deprescribing research: seizing opportunities and learning from the past Michael A. Steinman, MDUniversity of California, San Francisco and the San Francisco VA Medical CenterWord count: 1549References: 10Funding: This work was supported by the National Institute on Aging (grants R24AG064025 and K24AG049057)Disclosures: Dr. Steinman receives royalties from UpToDate and honoraria from the American Geriatrics Society. This manuscript is based on a lecture given at the First International Conference on Deprescribing (ICOD), Kolding, Denmark, September 2022.

Objective: Combining different drugs increases the potential for drug-drug interactions en-hancing the risk of adverse drug reactions. We aimed to unravel potential pharma-cokinetic interactions between aripiprazole and duloxetine. Methods: Plasma concentrations of aripiprazole of two groups of 78 patients each, receiving aripiprazole as a monotherapy, or combined with duloxetine, were compared. A po-tential impact of duloxetine on the metabolism of aripiprazole was expected in high-er plasma concentrations of aripiprazole and higher dose-adjusted plasma concen-trations. Results: Patients co-medicated with duloxetine showed significantly higher plasma concen-trations of aripiprazole (p=0.019) by 54.2%. Dose-adjusted plasma concentrations were 45.6% higher (p=0.001). 65.4 % of these patients exhibited aripiprazole plasma concentrations above the upper limit of the therapeutic reference range, in the con-trol group this was only the case for 43.6% of the patients (p=0.006). A positive rela-tionship was found between the daily dose of duloxetine and dose-adjusted plasma concentrations of aripiprazole (p=0.034). Conclusions: Combining duloxetine and aripiprazole leads to significantly higher drug concentra-tions of aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a lesser extent of CYP3A4 by duloxetine. Clinicians have to consider increasing aripiprazole concentrations when adding duloxetine to a treatment regimen with ari-piprazole.

Understanding landscape connectivity has become a global priority for mitigating the impact of landscape fragmentation on biodiversity. Link-based methods traditionally rely on relating pairwise genetic distance between individuals or demes to their landscape distance (e.g., geographic distance, cost distance). In this study, we present an alternative to conventional statistical approaches to refine cost surfaces by adapting the Gradient Forest (GF) approach to produce a resistance surface. Used in community ecology, GF is an extension of random forest (RF), and has been implemented in genomic studies to model species genetic offset under future climatic scenarios. By design, this adapted method, resGF, has the ability to handle multiple environmental predicators and is not subjected to traditional assumptions of linear models such as independence, normality and linearity. Using genetic simulations, resGF performance was compared to other published methods. In univariate scenarios, resGF was able to distinguish the true surface contributing to genetic diversity among competing surfaces better than the compared methods. In multivariate scenarios, the GF approach performed similarly to the other RF-based approach using least-cost transect analysis (LCTA). Additionally, two worked examples are provided using two previously published datasets. This machine learning algorithm has the potential to improve our understanding of landscape connectivity and can inform long-term biodiversity conservation strategies.

Bioretention is widely used in urban sustainable stormwater management. However, limited numerical research has been conducted on its performance in cold regions, particularly for winter snowmelt, spring runoff and summer large storms (> 50 mm) for urban flood mitigation. In this study, HYDRUS 1D was used to explore these knowledge gaps. The model was comprehensively calibrated and validated against 2-year hydrologic and water quality data of four bioretention columns with different designs under lab-simulated cold region conditions. The Morris method was used to measure the sensitivity and interaction of the calibrated hydraulic parameters. The model revealed that the effective hydraulic conductivity ( KS) values of the soil media were similar for winter snowmelt and spring runoff when the soil temperature was around -0.5 °C. Preferential flow is likely to occur in soil media during winter or spring of cold regions. The summer modeling showed that the bioretention could substantially reduce peak flow, ponding depth and duration for large storm events (even for 1:100 local storm with 83.4 mm in 4 hours). The water quality modeling confirmed experimental results that the bioretention effectively removed phosphate and ammonium but had leaching issues for chloride and nitrate. Finally, optimization and recommendations of bioretention columns were provided.

Context – The negative effects of socioeconomic, environmental and ethnic inequalities on childhood respiratory diseases are known in the development of persistent asthma and can result in adverse outcomes. However, little is known about the effects of these disparities on pediatric intensive care unit (PICU) outcomes in respiratory diseases. Objective – The purpose of this systematic review is to evaluate the literature on disparities in socioeconomic, environmental and ethnic determinants on PICU outcomes. We hypothesize that these disparities negatively influence the outcomes of children’s respiratory diseases at the PICU. Methods – A literature search (in PubMed, Embase.com and Web of Science Core Collection) was performed up to September 30, 2022. Two authors extracted the data and independently evaluated the risk of bias with appropriate assessment methods. Articles were included if the patients were below 18 years of age (excluding neonatal intensive care unit admissions), they concerned respiratory diseases and incorporated socioeconomic, ethnic or environmental disparities. Results – Of 8746 references reviewed, 15 articles were included; seven articles on the effect of socioeconomic status, five articles on ethnicity, one on the effect of sex and lastly two on environmental factors. All articles but one showed an unfavorable outcome at the PICU. Conclusion – Disparities in socioeconomic (such as a low-income household, public health insurance), ethnic and environmental factors (such as exposure to tobacco smoke and diet) have been assessed as risk factors for the severity of children’s respiratory diseases and can negatively influence the outcomes of these children at the PICU.

Individual differences in face memory abilities have been shown to be related to individual differences in brain activity. The present study investigated brain-behavior relationships for the N250 component in event-related brain potentials, which is taken as a neural sign of face familiarity. We used a task in which a designated, typical target face and several (high- and low-distinctive) nontarget faces had to be distinguished during multiple presentations across a session. Separately, face memory/recognition abilities were measured with easy versus difficult tasks. We replicated an increase of the N250 amplitude to the target face across the session and observed a similar increase for the non-target faces, indicating the build-up of memory representations also for these faces. On the interindividual level, larger across-session N250 amplitude increases to low-distinctive non-target faces were related to faster face recognition as measured in an easy task. These findings extend the present knowledge about brain-behavior relationships in face memory/recognition and indicate that an advantage in non-intentional encoding of low-distinctive non-target faces into memory goes along with the swift recognition of explicitly learned faces.

Catalytic reactors for carrying out endothermic or exothermic reactions are of great importance in the particular examples being reactors for the endothermic steam reforming of methanol and reactors for the exothermic catalytic combustion reaction. The present study aims to provide a fundamental understanding of the exothermic and endothermic reaction characteristics and operation methods of integrated combustion-reforming reactors. Particular emphasis is placed upon the simultaneous implementation of the endothermic steam reforming and the heat-supplying exothermic catalytic combustion such that the thermal stability of the reaction system is increased. The effect of catalyst layer thickness on the reaction characteristics is investigated in order to understand how to design and operate such reactors with high efficiency. The results indicate that unique jet design features can be implemented in order to suppress homogeneous combustion and promote heterogeneous catalytic combustion on the channel wall. Diffusion within these small pores in the catalyst layers is typically Knudsen in nature for gas phase systems, whereby the molecules collide with the walls of the pores more frequently than with other gas phase molecules. The composition in the combustion chamber is reacted to produce sufficient heat to sustain the micro-combustion process without energy input. The combustion and reforming processes can be stably and efficiently operated at lower temperatures, without the need for energy input to sustain or even to start the combustion process. Since a palladium component is alloyed with the zinc, generation of carbon monoxide due to the methanol decomposition reaction is suppressed. Direct heating is of considerable advantage as it largely overcomes the problems encountered with reaction rates being limited by the rate of heat transfer through the tube wall especially near the reformer entrance. The conventional methods are suitable for large scale hydrogen gas production, but they are not adequate for middle to small scale hydrogen gas production. As the channel dimension nears the quench diameter or drops below, the contribution of the unwanted gas phase homogeneous combustion reaction is reduced.Keywords: Catalytic reactors; Reaction characteristics; Heat exchange; Carbon monoxide; Partial oxidation; Thermal stability

Objective: The present study aimed to characterise the intersecting sociodemographic, psychiatric and substance use needs of young people seeking treatment across multiple primary mental health, justice and alcohol and drug services within Australia. Methods: Data from four separate studies (N = 867) that investigated social and emotional wellbeing in young people aged 16-25-years-old were used in the present study (three studies recruited service users; one study recruited community participants) Results: The sociodemographic characteristics of service users differed substantially to the community sample. Service users identified as non-binary, LGBTIQ+ and Aboriginal and/or Torres Strait Islander at substantially greater proportions compared to the community sample. Family violence, involvement in criminal justice, homelessness and child protection services was considerably more common among service users than in the community sample and nearly one-third of service users were disengaged from opportunities for learning and vocational attainment. With respect to psychiatric characteristics, the majority of service users had been diagnosed with two or more psychiatric disorders and, almost two- thirds reported engagement in non-suicidal self- injury across their lifetime. Service users engaged in lower rates of lifetime and harmful alcohol use compared to the community sample; however, they reported significantly higher rates of lifetime and harmful drug use with more than one-third of service users engaged in poly-substance use. Conclusion: The comprehensive examination of the sociodemographic, psychiatric and substance use characteristics of young service users in the present study highlights the intersection of early childhood adversity, adolescent mental ill-health, polysubstance use and psychosocial vulnerabilities across multiple determinants of social and emotional wellbeing. The cohort were indeed representative of some of the most vulnerable in our society. The need for developmentally informed, inter-sectoral systems of care that address the intersecting vulnerabilities of these young Australian service users are discussed