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Social functioning of children with experiences of intimate partner violence (IPV) between caregivers in early childhood has received less attention than emotional-behavioral outcomes. Drawing on data from 1507 ten-year-old Australian-born children and their mothers participating in a community-based longitudinal study, this study examined the associations between IPV exposure during infancy and social development during middle childhood. IPV during the first 12 months of life was associated with lower social skills, higher peer problems, and peer victimization at age 10 years, while accounting for concurrent IPV. This study provides evidence for the long-term impacts of early-life IPV exposure on children's social functioning, and the importance of prevention and early intervention programs focused on social development following experiences of IPV.

BACKGROUND: Obstetric fistula develops from obstructed labor and is a devastating condition with significant consequences across several domains of a woman's life. This study presents a narrative review of the evidence on the economic consequences of obstetric fistula. METHODS: Three databases were searched, and search results were limited to English language papers published after 2003. Search results were reviewed for relevance based on title and abstract followed by full text review using specific inclusion and exclusion criteria. Bibliographies of papers were also scanned to identify relevant papers for inclusion. Data were extracted under three categories (defined a priori): the economic consequences of having the condition, the economic consequences of seeking care, and the macroeconomic impacts. RESULTS: The search returned 517 unique papers, 49 of which were included after screening. Main findings identified from the studies include women losing their jobs, becoming dependent on others, and losing financial support when relationships are lost. Seeking care was economically costly for families or unaffordable entirely. There were no studies describing the impact of fistula on national economies. CONCLUSION: Economic consequences of obstetric fistula are multifaceted, pervasive, and are intertwined with the physical and psychosocial consequences of the condition. Understanding these consequences can help tailor existing fistula programs to better address the impacts of the condition. Further research to address the dearth of literature describing the macroeconomic impact of obstetric fistula will be critical to enhance the visibility of this condition on the health agendas of countries.

Subacromial impingement (SAI) is associated with shoulder pain and dysfunction and is exacerbated by rotator cuff tears; however, the role of acromioplasty in mitigating subacromial contact in the rotator cuff deficient shoulder remains debated. This study aimed to quantify the influence of isolated and combined tears involving the supraspinatus on subacromial contact during abduction; and second, to evaluate the influence of acromioplasty on joint space size and subacromial contact under these pathological conditions. Eight fresh-frozen human cadaveric upper limbs were mounted to a computer-controlled testing apparatus that simulated joint motion by simulated force application. Shoulder abduction was performed while three-dimensional joint kinematics was measured using an optoelectronic system, and subacromial contact evaluated using a digital pressure sensor secured to the inferior acromion. Testing was performed after an isolated tear to the supraspinatus, as well as tears involving the subscapularis and infraspinatus-teres minor, both before and after acromioplasty. Rotator cuff tears significantly increased peak subacromial pressure (p < 0.001), average subacromial pressure (p = 0.001), and contact force (p = 0.034) relative to those in the intact shoulder. Following acromioplasty, significantly lower peak subacromial contact pressure, force and area were observed for all rotator cuff tears involving the supraspinatus at 30° of abduction (p < 0.05). Acromioplasty predominantly reduces acromion thickness anteriorly thereby reducing subacromial contact in the rotator cuff deficient shoulder, particularly in early to mid-abduction where superior glenohumeral joint shear force potential is large. These findings provide a biomechanical basis for acromioplasty as an intervention for SAI syndrome and as an adjunct to rotator cuff repairs.

OBJECTIVE: This systematic review and meta-analysis aimed to update the literature on orthorexia nervosa (ON), a proposed diagnosis of pathologically 'healthy' eating, by critically analysing the current evidence for the relationship between ON and obsessive-compulsive (OC) symptoms. Further, this paper aimed to compare the ON/OC relationship significance and strength based on when the ON measurement tool was developed. METHOD: PsycINFO, PubMed and Web of Science databases were queried for quantitative, peer-reviewed studies recruiting adult participants, published in English up to April 2023. Studies not directly comparing ON and OC symptoms were excluded. After full-text review and quality assessment, 40 studies were included in the systematic review and 31 studies in the meta-analysis. RESULTS: ON assessments created prior to the 2016 revised ON diagnostic criteria do not appear to fully capture OC symptoms. Studies using earlier developed ON assessments demonstrated inconsistent ON/OC relationships whereas studies implementing more recent assessments (from 2018 onwards) found consistently significant, larger relationships, highlighting a previously underrated OC component of ON. CONCLUSIONS: Early ON studies, and studies utilising early ON assessments should be interpreted with caution, particularly in relation to OC symptom involvement in ON. Future research should validate novel ON assessments and investigate common underlying factors.

The distal colon and rectum (colorectum) are innervated by spinal and vagal afferent pathways. The central circuits into which vagal and spinal afferents relay colorectal nociceptive information remain to be comparatively assessed. To address this, regional colorectal retrograde tracing and colorectal distension (CRD)-evoked neuronal activation were used to compare the circuits within the dorsal vagal complex (DVC) and dorsal horn (thoracolumbar [TL] and lumbosacral [LS] spinal levels) into which vagal and spinal colorectal afferents project. Vagal afferent projections were observed in the nucleus tractus solitarius (NTS), area postrema (AP), and dorsal motor nucleus of the vagus (DMV), labeled from the rostral colorectum. In the NTS, projections were opposed to catecholamine and pontine parabrachial nuclei (PbN)-projecting neurons. Spinal afferent projections were labeled from rostral through to caudal aspects of the colorectum. In the dorsal horn, the number of neurons activated by CRD was linked to pressure intensity, unlike in the DVC. In the NTS, 13% ± 0.6% of CRD-activated neurons projected to the PbN. In the dorsal horn, at the TL spinal level, afferent input was associated with PbN-projecting neurons in lamina I (LI), with 63% ± 3.15% of CRD-activated neurons in LI projecting to the PbN. On the other hand, at the LS spinal level, only 18% ± 0.6% of CRD-activated neurons in LI projected to the PbN. The collective data identify differences in the central neuroanatomy that support the disparate roles of vagal and spinal afferent signaling in the facilitation and modulation of colorectal nociceptive responses.

Though it is often said that climate change is a risk to people's well‐being, the specific ways in which it affects people's well‐being is still poorly understood, especially as it relates to Indigenous Peoples and Local Communities. Two interrelated issues contribute to this gap in knowledge: (1) the use of different conceptualizations of well‐being across disciplines; and (2) the limited use of local and context‐specific understandings of well‐being that are meaningful to people exposed to climate change. Here, we review 103 articles covering the topic of climate change adaptation and well‐being. We find that, despite the growing interest on the topic, most of the articles do not include definitions of well‐being. We then propose an approach informed by emic values to better understand how climate change may affect well‐being in Indigenous Peoples and Local Communities. We conclude that, given the increasing recognition of well‐being as a fundamental marker of successful adaptation, well‐being should be central to climate change research and policymaking, but for this to be of benefit to Indigenous Peoples and Local Communities context‐specific understandings of well‐being are necessary. This article is categorized under: Vulnerability and Adaptation to Climate Change > Values‐Based Approach to Vulnerability and Adaptation Climate and Development > Sustainability and Human Well‐Being The Social Status of Climate Change Knowledge > Sociology/Anthropology of Climate Knowledge

BACKGROUND: Antimicrobial stewardship programmes (ASPs) are critically important for improving the appropriate use of antimicrobial agents in veterinary practice. METHODS: One of three ASPs was implemented in 135 Australian general veterinary practices in 2018-2020. The ASP interventions and the perceived impact they had on antimicrobial prescribing were assessed by the veterinarians working in these veterinary practices. An online survey was distributed to all 520 veterinarians working in the trial practices and 267 responses were analysed. RESULTS: Most veterinarians (174/267, 65%) thought they had an ASP at their clinic and most respondents who said that they were aware that they had an ASP at their clinic indicated that they had changed the way they prescribed antimicrobials because of the trial (125/170, 74%). Antimicrobial prescribing guidelines, the traffic light system for indicating antimicrobial importance, delayed prescribing and antimicrobial stewardship champions were reported to have had the biggest impact. LIMITATIONS: All practices in the trial belong to a single corporate group, which may impact the external validity of these results when applied to general small animal practice. CONCLUSION: Antimicrobial stewardship has a positive impact on antimicrobial prescribing in veterinary medicine and future interventions should focus on the implementation of the effective interventions identified in this study.

Benefiting from the synergistic development of material design, device engineering, and the mechanistic understanding of device physics, the certified power conversion efficiencies (PCEs) of single-junction non-fullerene organic solar cells (OSCs) have already reached a very high value of exceeding 19%. However, in addition to PCEs, the poor stability is now a challenging obstacle for commercial applications of organic photovoltaics (OPVs). Herein, recent progress made in exploring operational mechanisms, anomalous photoelectric behaviors, and improving long-term stability in non-fullerene OSCs are highlighted from a novel and previously largely undiscussed perspective of engineering exciton and charge carrier pathways. Considering the intrinsic connection among multiple temporal-scale photocarrier dynamics, multi-length scale morphologies, and photovoltaic performance in OPVs, this review delineates and establishes a comprehensive and in-depth property-function relationship for evaluating the actual device stability. Moreover, this review has also provided some valuable photophysical insights into employing the advanced characterization techniques such as transient absorption spectroscopy and time-resolved fluorescence imagings. Finally, some of the remaining major challenges related to this topic are proposed toward the further advances of enhancing long-term operational stability in non-fullerene OSCs.

INTRODUCTION: Intimate partner violence (IPV) disproportionally affects women compared to men. The impact of IPV is amplified during pregnancy. Screening or enquiry in the antenatal outpatient setting regarding IPV has been fraught with barriers that prevent recognition and the ability to intervene. AIMS: The aim of this systematic review was to determine the barriers that face obstetricians/gynaecologists regarding enquiry of IPV in antenatal outpatient settings. The secondary objective was to determine facilitators. METHODS: Primary evidence was searched using Ovid MEDLINE, Ovid Maternity and Infant Care, PubMed and Proquest from 1993 to May 2023. The included studies comprised empirical studies published in English language targeting a population of doctors providing antenatal outpatient care. The review was PROSPERO-registered (CRD42020188994). Independent screening and review was performed by two authors. The findings were analysed thematically. RESULTS: Nine studies addressing barriers and two studies addressing facilitators were included: three focus-group or semi-structured interviews, six surveys and two randomised controlled trials. Barriers for providers centred at the system level (time, training), provider level (personal beliefs, cultural bias, experience) and provider-perceived patient level (fear of offending, patient readiness to disclose). Increased experience and the use of validated tools were strong facilitators. CONCLUSION: Barriers to screening reflect multi-level obstruction to the identification of women exposed to IPV. Although the antenatal outpatient clinic setting addresses a particular population vulnerable to IPV, the barriers for obstetricians are not unique. The use of validated cueing tools provides an evidence-based method to facilitate enquiry of IPV among antenatal women, assisting in identification by clinicians. Together with education and human resources, such aids build capacity in women and obstetric providers.

People keep secrets for years with significant ramifications if the information were ever revealed. How can we understand the effects of long-held secrets? The current paper presents a new perspective on secrecy and how it can be studied. By examining the multiple experiences people have with their multiple secrets, we can obtain a fuller view of how secrets affect people in daily life. Additionally, by examining a set of common secrets, across people, we can understand how secrets (i.e., exemplars) differ from one another, and we can study how those differences relate to important variables like well-being. That is, rather than study a specific secret or secrecy situation (which will have limited generalizability), we can seek to study the entire universe of secrets, both to make generalizations across that universe and to compare different secrets to one another. Using the question of whether secrecy causes lower well-being, we discuss this Multiple Exemplar Measurement approach alongside other methodologies. We highlight the many benefits of taking an exemplar-level perspective, both for understanding secrecy and other psychological phenomena more broadly.

OBJECTIVE: Disease metabolomes have been studied for identifying diagnostic and predictive biomarkers of pathology. Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent subtypes of head and neck squamous cell carcinoma, yet the profile and diagnostic value of its tissue metabolite are unclear. SUBJECTS AND METHODS: Tumor tissue samples and matched normal mucosal tissue samples were collected from 40 OTSCC patients. Untargeted metabolic analysis by liquid chromatography-mass spectrometry/mass spectrometry, in positive and negative ion modes, was used to identify dysregulated metabolites in OTSCC. Further, utilizing LASSO regression and receiver operating characteristic analyses, biomarker metabolites were selected and validated, and a diagnostic model was established. RESULTS: One hundred and ninety metabolites were detected. The OTSCC had a total of 89 dysregulated metabolites, of which 73 were elevated. A diagnostic panel of nine metabolites was subsequently created that could accurately identify OTSCC with 100% sensitivity of 100%, 100% specificity and an AUC of 1.00. CONCLUSIONS: This study identified distinct metabolic characteristics of OTSCC and established a diagnostic model. Our research also contributes to the investigation of the pathogenesis of OTSCC.

Indeed, NSO reported to the United Nations Office on Drugs and Crime between 2015 and 2019 grew from 2 to 8% of all reported novel psychoactive substances. To date, little has been published on non-fentanyl synthetic opioid use in Australia. AP-238 and 2-Methyl AP-237 are non-fentanyl synthetic opioids, which exhibit µ-opioid receptor agonism with substantially lower potency than fentanyl. 2-Methyl AP-237 was first identified in 2019 in drug seizures as an encapsulated white powder and in forensic toxicological analysis in Europe and the United States (US). AP-238 was first identified within the illicit drug market in the US and Slovenia in 2020. We report a case of analytically confirmed 2-methyl AP-237 and AP-238 use in a patient presenting to an emergency department, as part of the Emerging Drugs Network of Australia - Victoria project.

Background Nucleic acid test window periods for HIV, HCV, and HBV facilitate estimation of the residual risk of unexpected disease transmission and assist clinicians in determining the timeframe in which a recently acquired infection is at risk of nondetection. Objectives Firstly, to provide revised estimates of the NAT window periods based on a currently used triplex NAT assay. Secondly, to examine their validity in organ donation and transplantation practice. Method Estimates were based on the Procleix Ultrio Elite Assay (Grifols Diagnostic Solutions Inc. California, USA). The manufacturer's X50 and X95 limits of detection (LOD) were utilised. Viral doubling times of 0.85, 0.45, and 2.56 days and conversion factors for IU per ml to copies per mL of 0.6, 3.4, and 5 were assumed for HIV, HCV, and HBV respectively. Window periods were derived from the X50 and X95 LODs, based on a range of potential inoculum volumes. Results Calculated X50 window periods were 5.1 (4.5–5.8), 2.7 (2.4–2.9), and 16.6 (14.2–19.1) days for HIV, HCV, and HBV respectively. Calculated X50 window periods, based on whole body plasma volume, were 11.8 (10.3–13.3), 6.2 (5.6–6.8) and 36.7 (31.3–42.1) days respectively. Conclusion X50 NAT window periods were significantly shorter for HBV and HCV and sit at the lower range of previously published estimates for HIV . Current modeling assumptions may not account for all unexpected transmission events and may no longer be suitable for application to organ donation and transplantation.

BACKGROUND AND OBJECTIVE: Early-life risk factors for obstructive sleep apnoea (OSA) are poorly described, yet this knowledge may be critical to inform preventive strategies. We conducted the first study to investigate the association between early-life risk factors and OSA in middle-aged adults. METHODS: Data were from population-based Tasmanian Longitudinal Health Study cohort (n = 3550) followed from 1st to 6th decades of life. Potentially relevant childhood exposures were available from a parent-completed survey at age 7-years, along with previously characterized risk factor profiles. Information on the primary outcome, probable OSA (based on a STOP-Bang questionnaire cut-off ≥5), were collected when participants were 53 years old. Associations were examined using logistic regression adjusting for potential confounders. Analyses were repeated using the Berlin questionnaire. RESULTS: Maternal asthma (OR = 1.5; 95% CI 1.1-2.0), maternal smoking (OR = 1.2; 1.05, 1.5), childhood pleurisy/pneumonia (OR = 1.3; 1.04, 1.7) and frequent bronchitis (OR = 1.2; 1.01, 1.5) were associated with probable OSA. The risk-factor profiles of 'parental smoking' and 'frequent asthma and bronchitis' were also associated with probable OSA (OR = 1.3; 1.01, 1.6 and OR = 1.3; 1.01-1.9, respectively). Similar associations were found for Berlin questionnaire-defined OSA. CONCLUSIONS: We found novel temporal associations of maternal asthma, parental smoking and frequent lower respiratory tract infections before the age of 7 years with adult OSA. While determination of their pathophysiological and any causal pathways require further research, these may be useful to flag the risk of OSA within clinical practice and create awareness and vigilance among at-risk groups.

Female carriers of X-linked inherited retinal diseases (IRDs) are burdened with potentially passing their disease-causing variant to future generations, as well as exhibiting signs of retinal disease themselves. This study aimed to investigate carriers' experiences of genetic testing, emotions relating to having affected children, and their knowledge regarding genetic testing and gene therapy. An online survey was advertised to self-identified carriers worldwide. Two hundred and twenty-eight carriers completed the survey with mean age of 51 years (SD ± 15.0). A majority of respondents resided in the United States of America (51%), Australia (19%), and the United Kingdom (14%). Most carriers identified with feelings of guilt (70%), concern (91%), and anxiety (88%) for their child. Female carriers who had given birth to children had significantly greater gene therapy knowledge compared to carriers who had not (p < 0.05). Respondents agreed that their eyecare provider and general practitioner helped them understand their condition (63%), however, few carriers reported receiving psychological counselling (9%) or family planning advice (5%). Most respondents (78%) agreed that gene therapy should be available to carriers. This study emphasises the importance of providing appropriate counselling to female carriers and illustrates the motivation of many to participate in emerging treatment options, such as gene therapy.

Enhancing disaster risk reduction (DRR) and community resilience are fundamental for sustainable development. However, cultural and political-institutional barriers hinder governments from progressing towards sustainability. We propose a redesign of social impact assessment (SIA) to make it more applicable to the field of regional and urban planning, and we discuss the role SIA can have in enhancing community resilience to achieve DRR and sustainable development in localities. We argue that, to convert SIA into a tool that can inform regional recovery and development planning, a rethinking of SIA and of the role of SIA practitioners is needed. We therefore expound the SIA Framework for Action and we enhance it to be a community-based process focussed on informing regional policies and plans and decisions about the projects to be included in such plans. Application of the SIA Framework for Action will help governments overcome the barriers to DRR and sustainable development.

OBJECTIVE: To present the early results of a new technique for the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome. PATIENTS AND METHODS: The first stage involves transdiaphragmatic debulking of the right heart, inferior vena cava (IVC) and hepatic veins via median sternotomy, followed by a purse-string suture placed in the IVC below the hepatic veins. The second stage is performed separately and involves en bloc resection of the affected kidney, and IVC and vascular reconstruction via an abdominal incision. RESULTS: Three of five patients presented with clinical Budd-Chiari syndrome; two had radiological features only. The median time between surgical procedures was 12 days (IQR 13 days). Four of the five patients had a R0 resection. While all five patients successfully completed both operative stages, one patient died 22 days after the second stage. Of the remaining four, all survive with no disease recurrence. CONCLUSION: While we continue to compile longer-term data for a larger follow-up series, these preliminary findings show the feasibility of this technique and support the development of this programme of surgery.

Lipids play a significant role in maintaining central nervous system (CNS) structure and function, and the dysregulation of lipid metabolism is known to occur in many neurological disorders, including Alzheimer's disease. Here we review what is currently known about lipid dyshomeostasis in Alzheimer's disease. We propose that small extracellular vesicle (sEV) lipids may provide insight into the pathophysiology and progression of Alzheimer's disease. This stems from the recognition that sEV likely contributes to disease pathogenesis, but also an understanding that sEV can serve as a source of potential biomarkers. While the protein and RNA content of sEV in the CNS diseases have been studied extensively, our understanding of the lipidome of sEV in the CNS is still in its infancy.

Accurately predicting weather and climate in cities is critical for safeguarding human health and strengthening urban resilience. Multimodel evaluations can lead to model improvements; however, there have been no major intercomparisons of urban‐focussed land surface models in over a decade. Here, in Phase 1 of the Urban‐PLUMBER project, we evaluate the ability of 30 land surface models to simulate surface energy fluxes critical to atmospheric meteorological and air quality simulations. We establish minimum and upper performance expectations for participating models using simple information‐limited models as benchmarks. Compared with the last major model intercomparison at the same site, we find broad improvement in the current cohort's predictions of short‐wave radiation, sensible and latent heat fluxes, but little or no improvement in long‐wave radiation and momentum fluxes. Models with a simple urban representation (e.g., ‘slab’ schemes) generally perform well, particularly when combined with sophisticated hydrological/vegetation models. Some mid‐complexity models (e.g., ‘canyon’ schemes) also perform well, indicating efforts to integrate vegetation and hydrology processes have paid dividends. The most complex models that resolve three‐dimensional interactions between buildings in general did not perform as well as other categories. However, these models also tended to have the simplest representations of hydrology and vegetation. Models without any urban representation (i.e., vegetation‐only land surface models) performed poorly for latent heat fluxes, and reasonably for other energy fluxes at this suburban site. Our analysis identified widespread human errors in initial submissions that substantially affected model performances. Although significant efforts are applied to correct these errors, we conclude that human factors are likely to influence results in this (or any) model intercomparison, particularly where participating scientists have varying ex

The metal‐mediated exfoliation (MME) method enables monolayer‐selective exfoliation of van der Waals (vdW) crystals, improving the efficacy of large monolayer production. Previous physical models explaining monolayer‐selective MME propose that the main contributors to monolayer‐selectivity are vdW crystal/metal surface binding energy and/or vdW crystal layer strain resulting from lattice mismatch. However, the performance of some metals for MME is inconsistent with these models. Here, a new model is proposed using MoS2 as a representative vdW crystal. The model explains how the MoS2/metal interface electrostatics, in combination with strain, determines monolayer‐selectivity of MME by modulating the MoS2 interlayer energy. Monolayer MoS2/metal interfaces are characterized using in situ Raman spectroscopy and density functional theory calculations to estimate the electrostatics and strain of MoS2 in contact with different metals. The model successfully demonstrates the dependence of MME monolayer‐selectivity on the MoS2/metal interface electrostatics and highlights the significance of electrostatics in nanomaterial vdW interactions.

AIM: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12-month follow-up. METHODS: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. RESULTS: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. CONCLUSIONS: The SNAP study will test whether neurophenomenological disturbances associated with basic self-disturbance predict persistence or intensification of UHR symptomatology over a 2-year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis.

BACKGROUND AND AIMS: Poor substance use-related health outcomes after release from prison are common. Identifying people at greatest risk of substance use and related harms post-release would help to target support at those most in need. The Alcohol Smoking and Substance Involvement Screening Test (ASSIST) is a validated substance use screener, but its utility in predicting substance-related hospitalisation post-release is unestablished. We measured whether screening for moderate/high-risk substance use on the ASSIST was associated with increased risk of substance-related hospitalisation. DESIGN: A prospective cohort study. SETTING: Prisons in Queensland and Western Australia. PARTICIPANTS: Participants were incarcerated and within 6 weeks of expected release when recruited. A total of 2585 participants were followed up for a median of 873 days. MEASUREMENTS: Baseline survey data were combined with linked unit record administrative hospital data. We used the ASSIST to assess participants for moderate/high-risk cannabis, methamphetamine and heroin use in the 3 months prior to incarceration. We used International Classification of Diseases (ICD) codes to identify substance-related hospitalisations during follow-up. We compared rates of substance-related hospitalisation between those classified as low/no-risk and moderate/high-risk on the ASSIST for each substance. We estimated adjusted hazard ratios (aHR) by ASSIST risk group for each substance using Weibull regression survival analysis allowing for multiple failures. FINDINGS: During follow-up, 158 (6%) participants had cannabis-related, 178 (7%) had opioid-related and 266 (10%) had methamphetamine-related hospitalisation. The hazard rates of substance-related hospitalisation after prison were significantly higher among those who screened moderate/high-risk compared with those screening low risk on the ASSIST for cannabis (aHR 2.38, 95% confidence interval [CI] 1.74, 3.24), methamphetamine (aHR 2.23, 95%CI 1.75, 2.84

Our knowledge about the role of fly-in fly-out (FIFO) work-related factors on the well-being of workers across the FIFO work cycle is limited. This study examined the within-person effects of job demand and control on psychological states and health behaviours. The study employed a daily diary design, with 23 FIFO workers in the Australian mining industry completing a daily diary survey for 28 consecutive days across on-shift and off-shift periods. Multilevel analyses showed FIFO workers experienced higher positive affect and enjoyed better sleep quality, but consumed more alcohol, during off-shift days as compared to on-shift days. Within-person variability in daily demand (workload) was associated with higher anxious affect, whereas job control predicted lower anxious and depressed affects, higher positive affect, more alcohol consumption, and more physical activity. The within-person effect of demand on anxious affect was moderated by job control such that those who generally had more control over their jobs had a smaller effect of demand on anxiety than those with less control. Results suggest potentially modifiable aspects of FIFO work-particularly job control-may help alleviate the impact of workload on poorer health behaviours and mood.

BACKGROUND: Aboriginal and Torres Strait Islander people are ageing with high rates of comorbidity, yet little is known about suboptimal prescribing in this population. AIM: The prevalence of potentially suboptimal prescribing and associated risk factors were investigated among older patients attending primary care through Aboriginal Community Controlled Health Services (ACCHSs). METHODS: Medical records of 420 systematically selected patients aged ≥50 years attending urban, rural and remote health services were audited. Polypharmacy (≥ 5 prescribed medications), potentially inappropriate medications (PIMs) as per Beers Criteria and anticholinergic burden (ACB) were estimated and associated risk factors were explored with logistic regression. RESULTS: The prevalence of polypharmacy, PIMs and ACB score ≥3 was 43%, 18% and 12% respectively. In multivariable logistic regression analyses, polypharmacy was less likely in rural (odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.24-0.77) compared to urban patients, and more likely in those with heart disease (OR = 2.62, 95% CI = 1.62-4.25), atrial fibrillation (OR = 4.25, 95% CI = 1.08-16.81), hypertension (OR = 2.14, 95% CI = 1.34-3.44), diabetes (OR = 2.72, 95% CI = 1.69-4.39) or depression (OR = 1.91, 95% CI = 1.19-3.06). PIMs were more frequent in females (OR = 1.88, 95% CI = 1.03-3.42) and less frequent in rural (OR = 0.41, 95% CI = 0.19-0.85) and remote (OR = 0.58, 95% CI = 0.29-1.18) patients. Factors associated with PIMs were kidney disease (OR = 2.60, 95% CI = 1.37-4.92), urinary incontinence (OR = 3.00, 95% CI = 1.02-8.83), depression (OR = 2.67, 95% CI = 1.50-4.77), heavy alcohol use (OR = 2.83, 95% CI = 1.39-5.75) and subjective cognitive concerns (OR = 2.69, 95% CI = 1.31-5.52). High ACB was less common in rural (OR = 0.10, 95% CI = 0.03-0.34) and remote (OR = 0.51, 95% CI = 0.25-1.04) patients and more common in those with kidney disease (OR = 3.07, 95% CI = 1.50-6.30) or depression (OR = 3.32, 95% CI

OBJECTIVE: To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug-resistant focal epilepsy. METHODS: Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6-month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment-related variables were assessed by using a stepwise logistic regression model. RESULTS: At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re-assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow-up, whereas no association was identified with sociodemographic and epilepsy-related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6-month re-assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two-fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes. SIGNIFICANCE: Almost 1 in 5 adults with drug-resistant focal epilepsy who screen negative for depression become positive when re-assessed 6 months after a treatment change. At re-assessment 6 months later, 6.1% who scr

Indonesian rural youth face challenges accessing farmland and sustaining an agricultural livelihood while their labour is not necessarily absorbed by other sectors. In that context, the Omnibus Law on Job Creation (Law 11/2020) promises to liberalise trade and investment across multiple sectors, including agriculture and food security. Combining legal research and political economy approaches to youth and agrarian challenges, we identify amendments to legislation that reduce safeguards for the environment, workers' and farmers' rights and their livelihoods. If fully implemented, the legislative amendments could further narrow youth's options both for secure formal work and futures in farming by accelerating the expansion of infrastructure, industrial plantations and extractive industries that utilise low‐wage labour and huge areas of land. This exposes inconsistencies in the government's approach to increase future food security by promoting intensification of agriculture and attracting youth to farming, while enabling agro‐ and resource extraction that absorbs land yet offers limited and precarious employment prospects.

BACKGROUND: The COVID-19 pandemic and response changed clinical service delivery and practice for speech and language therapists (SLTs) in the United Kingdom. SLTs work with children with neurodisability regarding both difficulties with their communication and eating and drinking skills (oropharyngeal dysphagia). This survey aimed to specifically explore the impact of the COVID-19 pandemic on SLT practice for school-aged children with dysphagia. METHODS: UK-based SLTs working with school-aged children with neurodisability and oropharyngeal dysphagia were recruited to share their perceptions on the impact of COVID-19 on practice. Four questions focusing on COVID-19 impact were part of a larger online survey exploring SLT clinical practice regarding mealtime management of children with neurodisability and oropharyngeal dysphagia, which included demographic information, service delivery, assessment and intervention practices. COVID-19 impact questions were a mixture of multiple choice and free text responses. The survey was disseminated using professional networks and social media, between 14 May and 30 July 2021. Data were analysed using descriptive statistics and qualitative content analysis. RESULTS: One hundred and two participants answered at least one of the four COVID-19 questions. Eighty-two per cent of SLTs either agreed or strongly agreed that COVID-19 impacted on service delivery to children and families. Negative impacts on service delivery included school absences/closures, home visiting restrictions, families declining input and/or having barriers to telehealth use and the impact of mask wearing on interactions. Positive impacts included increased telehealth access and skills, increased contact with families and focus on children's eating and drinking function within the home environment. Participants aimed to maintain the increased contact with families alongside a hybrid service delivery approach of in-person and virtual appointments. CONCLUSIONS: This

OBJECTIVE: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment-resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS. METHODS: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent-reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0 years:months (Y:M; youngest), 2:1-3:6 Y:M (middle), and 3:7-5:0 Y:M (oldest). RESULTS: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow-up was 17.5 months (range = .0-24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum-maximum] = 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [.0-2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, p = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores. SIGNIFICANCE: In infants and young children with SCN1A+ DS, language/communication delay and st

Cryptic diversity is common among marine macroalgae, with molecular tools leading to the discovery of many new species. To assign names to these morphologically similar species, the type and synonyms have to be examined, and if appropriate, new species must be described. The turf-forming red alga Polysiphonia scopulorum was originally described from Rottnest Island, Australia, and subsequently widely reported in tropical and temperate coasts based on morphological identifications. A recent study of molecular species delineation revealed a complex of 12 species in Australia, South Africa, and Europe. These species are placed in a taxonomically unresolved lineage of the tribe Polysiphonieae. The aim of this study was to resolve the genus- and species-level taxonomy of this complex and related species using molecular and morphological information. Three morphologically indistinguishable species of the complex were found at the type locality of P. scopulorum, preventing a straightforward assignment of the name to any of the molecular lineages. Therefore, we propose a molecularly characterized epitype. Polysiphonia caespitosa is reinstated for the only species found in its type locality in South Africa. We describe seven new species. Only one species of the complex can be morphologically recognized, with the other eight species indistinguishable based on morphometric analysis. The studied complex, together with another seven species currently placed in Polysiphonia and two Bryocladia species, formed a clade distinct from Polysiphonia sensu stricto. Based on observations of Bryocladia cervicornis (the generitype), we describe our seven new species in the genus Bryocladia and transfer another nine species from Polysiphonia to Bryocladia.

The nondestructive localization and traceability of polymers by fluorescent tagging has become a valuable tool for biomedical applications. Integration of fluorescent molecule to the pristine polymers could modify polymers' degradation rate which is still unpredictable from a scaffold application standpoint. The current study focused to understand the material perspective of fluorescently tagged biodegradable polymers such as polycaprolactone (PCL) and poly (d,l‐lactide‐co‐glycolide) (PLGA) with fluorescein amine isomer I (FITC). PCL‐FITC and PLGA‐FITC were characterized using FTIR for surface chemistry analysis and rheology for their mechanical properties. The grafted materials were utilized to form 3‐dimentional scaffolds, and their degradation was monitored under accelerated degradation conditions triggered by pH. It was found that PCL and PCL‐FITC had a very slow degradation rate, when compared to PLGA and PLGA‐FITC. Both the FITC tagged materials displayed a faster degradation rate compared to their respective pristine material. Biocompatibility of the FITC conjugated polymers was tested using human‐adipose derived stem cells (hADSCs) revealing that the sub products from the degradation of the polymers over 7 days did not negatively affect the cellular metabolic activity. This work highlights the significance of initial characterization of fluorescent modified polymers for future biomedical application.

AIMS: The Raising Awareness Tool for Endometriosis (RATE) was developed to facilitate discussions with health providers regarding endometriosis-associated symptoms. We aim to evaluate the acceptability of the RATE by general practitioners (GP), including determining the prevalence of symptoms of women presenting to general practice and immediate management of symptoms. METHODS: A mixed-methods study was undertaken using a combination of quantitative and qualitative data in Western Australian General Practices from 2021 to 2022. A purposive sample of 12 GPs were included, who recruited women (18-50 years) on attendance for consultation over a one- to two-week period, followed by qualitative interviews exploring GPs' experiences with the tool. The quantitative and qualitative components were integrated during analysis of results. RESULTS: A total of 111 women completed the RATE (mean: 33, standard deviation: 8.6 years) prior to routine consultation. The tool was considered to be acceptable for use in general practice and aided discussions on symptoms and management. Overall, 68.5% of patients experienced pelvic pain or discomfort, with 22.4% rating that this interfered with quality of life. Of those with pelvic pain, 75% had associated chronic pain conditions, and 42.1% reported allodynia. The chronic pain questions provoked GP uncertainty. After symptoms were identified, GPs arranged individualised investigations and follow-up. CONCLUSIONS: The RATE was considered to be acceptable for use in the general practice setting. It identified symptoms and initiated discussions on possible diagnosis as well as management of endometriosis. Further GP education on identifying those women at most risk of developing chronic pain syndromes is needed.

The application of lipid-based nanoparticles for COVID-19 vaccines and transthyretin-mediated amyloidosis treatment have highlighted their potential for translation to cancer therapy. However, their use in delivering drugs to solid tumors is limited by ineffective targeting, heterogeneous organ distribution, systemic inflammatory responses, and insufficient drug accumulation at the tumor. Instead, the use of lipid-based nanoparticles to remotely activate immune system responses is an emerging effective strategy. Despite this approach showing potential for treating hematological cancers, its application to treat solid tumors is hampered by the selection of eligible targets, tumor heterogeneity, and ineffective penetration of activated T cells within the tumor. Notwithstanding, the use of lipid-based nanoparticles for immunotherapy is projected to revolutionize cancer therapy, with the ultimate goal of rendering cancer a chronic disease. However, the translational success is likely to depend on the use of predictive tumor models in preclinical studies, simulating the complexity of the tumor microenvironment (e.g., the fibrotic extracellular matrix that impairs therapeutic outcomes) and stimulating tumor progression. This review compiles recent advances in the field of antitumor lipid-based nanoparticles and highlights emerging therapeutic approaches (e.g., mechanotherapy) to modulate tumor stiffness and improve T cell infiltration, and the use of organoids to better guide therapeutic outcomes.

Orthotopic liver transplantation (OLT) in the care of children with inborn errors of metabolism (IEM) is well established and represent the second most common indication for pediatric liver transplantation in most centers worldwide, behind biliary atresia. OLT offers cure of disease when a metabolic defect is confined to the liver, but may still be transformative on a patient's quality of life reducing the chance of metabolic crises causing neurological damage in children be with extrahepatic involvement and no "functional cure." Outcomes post-OLT for inborn errors of metabolism are generally excellent. However, this benefit must be balanced with consideration of a composite risk of morbidity, and commitment to a lifetime of post-transplant chronic disease management. An increasing number of transplant referrals for children with IEM has contributed to strain on graft access in many parts of the world. Pragmatic evaluation of IEM referrals is essential, particularly pertinent in cases where progression of extra-hepatic disease is anticipated, with long-term outcome expected to be poor. Decision to proceed with liver transplantation is highly individualized based on the child's dynamic risk-benefit profile, their family unit, and their treating multidisciplinary team. Also to be considered is the chance of future treatments, such as gene therapies, emerging in the medium term.

OBJECTIVE: To evaluate the efficacy of sequential treatment with ipilimumab and nivolumab following progression on nivolumab monotherapy in individuals with advanced, non-clear-cell renal cell carcinoma (nccRCC). MATERIALS AND METHODS: UNISoN (ANZUP1602; NCT03177239) was an open-label, single-arm, phase 2 clinical trial that recruited adults with immunotherapy-naïve, advanced nccRCC. Participants received nivolumab 240 mg i.v. two-weekly for up to 12 months (Part 1), followed by sequential addition of ipilimumab 1 mg/kg three-weekly for four doses to nivolumab if disease progression occurred during treatment (Part 2). The primary endpoint was objective tumour response rate (OTRR) and secondary endpoints included duration of response (DOR), progression-free (PFS) and overall survival (OS), and toxicity (treatment-related adverse events). RESULTS: A total of 83 participants were eligible for Part 1, including people with papillary (37/83, 45%), chromophobe (15/83, 18%) and other nccRCC subtypes (31/83, 37%); 41 participants enrolled in Part 2. The median (range) follow-up was 22 (16-30) months. In Part 1, the OTRR was 16.9% (95% confidence interval [CI] 9.5-26.7), the median DOR was 20.7 months (95% CI 3.7-not reached) and the median PFS was 4.0 months (95% CI 3.6-7.4). Treatment-related adverse events were reported in 71% of participants; 19% were grade 3 or 4. For participants who enrolled in Part 2, the OTRR was 10%; the median DOR was 13.5 months (95% CI 4.8-19.7) and the median PFS 2.6 months (95% CI 2.2-3.8). Treatment-related adverse events occurred in 80% of these participants; 49% had grade 3, 4 or 5. The median OS was 24 months (95% CI 16-28) from time of enrolment in Part 1. CONCLUSIONS: Nivolumab monotherapy had a modest effect overall, with a few participants experiencing a long DOR. Sequential combination immunotherapy by addition of ipilimumab in the context of disease progression to nivolumab in nccRCC is not supported by this study, with only a minori

Aim: This study aimed to (1) quantify attention and executive functioning in chil-dren with developmental coordination disorder (DCD), (2) assess whether some chil-dren with DCD are more likely to show attention difficulties, and (3) characterizebrain correlates of motor and attention deficits.Method: Fifty-three children (36 with DCD and 17 without) aged 8 to 10 years un-derwent T1-weighted and diffusion-weighted magnetic resonance imaging, andstandardized attention and motor assessments. Parents completed questionnaires ofexecutive functioning and symptoms of inattention and hyperactivity. We assessedregional cortical thickness and surface area, and cerebellar, callosal, and primarymotor tract structure.Results: Analyses of covariance and one-sample t-tests identified impaired atten-tion, non-motor processing speed, and executive functioning in children with DCD,yet partial Spearman's rank correlation coefficients revealed these were unrelatedto one another or the type or severity of the motor deficit. Robust regression analy-ses revealed that cortical morphology in the posterior cingulate was associated withboth gross motor skills and inattentive symptoms in children with DCD, while grossmotor skills were also associated with left corticospinal tract (CST) morphology.Interpretation: Children with DCD may benefit from routine attention and hyper-activity assessments. Alterations in the posterior cingulate and CST may be linkedto impaired forward modelling during movements in children with DCD. Overall,alterations in these regions may explain the high rate of non-motor impairments inchildren with DCD.

BACKGROUND: Endometriosis is a chronic, inflammatory condition characterised by the presence of endometrial-like tissue outside the uterine cavity. Given the multi-system nature of the disease and the potential for significant negative impact on quality of life, there has been a long-standing recognition of the need for multidisciplinary care for people with endometriosis. However, there is paucity to the data supporting this approach, and much of the evidence is anecdotal. AIM: This systematic review aims to describe recent evidence-based models and patient-centred perspectives of multidisciplinary care for endometriosis, to improve understanding of the role of an integrated, multidisciplinary team in effectively addressing patients' care needs. MATERIALS AND METHODS: PubMed, Medline, Embase and Web of Science were searched for relevant articles published between 1 January 2010 to 7 July 2022. RESULTS: Nineteen studies met the inclusion and exclusion criteria and pinpointed a multidisciplinary team consisting of gynaecologists, pain specialists, nurses, physiotherapists, psychologists, sex therapists, nutritionists, complementary medicine practitioners, and social workers to be most commonly utilised in holistically managing people with pelvic pain and endometriosis. Furthermore, patient perspectives on care highlighted the need for reliable information, respect and validation of experiences or preferences, discussion of long-term treatment plans and social and emotional supports. CONCLUSION: The trend for multidisciplinary team care for people with endometriosis is growing. Further consumer-driven clinical studies and outcome evaluations need to be conducted to determine the effect of multidisciplinary care on improvements to quality of life for people living with endometriosis and or pelvic pain.

BACKGROUND AND PURPOSE: Understanding predictors of changes in employment status among people living with multiple sclerosis (MS) can assist health care providers to develop appropriate work retention/rehabilitation programs. We aimed to model longitudinal transitions of employment status in MS and estimate the probabilities of retaining employment status or losing or gaining employment over time in individuals with a first clinical diagnosis of central nervous system demyelination (FCD). METHODS: This prospective cohort study comprised adults (aged 18-59 years) diagnosed with FCD (n = 237) who were followed for more than 11 years. At each review, participants were assigned to one of three states: unemployed, part-time, or full-time employed. A Markov multistate model was used to examine the rate of state-to-state transitions. RESULTS: At the time of FCD, participants with full-time employment had an 89% chance of being in the same state over a 1-year period, but this decreased to 42% over the 10-year follow-up period. For unemployed participants, there was a 92% likelihood of remaining unemployed after 1 year, but this probability decreased to 53% over 10 years. Females, those who progressed to clinically definite MS, those with a higher relapse count, and those with a greater level of disability were at increased risk of transitioning to a deteriorated employment state. In addition, those who experienced clinically significant fatigue over the follow-up period were less likely to gain employment after being unemployed. CONCLUSIONS: In our FCD cohort, we found a considerable rate of employment transition during the early years post-diagnosis. Over more than a decade of follow-up post-FCD, we found that females and individuals with a greater disability and a higher relapse count are at higher risk of losing employment.

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. METHODS: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. A

Accurate mediastinal staging remains the cornerstone of treatment decision-making in non-metastatic non-small cell lung cancer (NSCLC). Beyond prognostication, N-status holds significant importance in differentiating patients whose disease is potentially suitable for surgical resection (traditionally N0/1) from those with locally advanced disease (N2/3) who are recommended for combination chemoradiotherapy.

Apicomplexan haemoparasites generate significant morbidity and mortality in humans and other animals, particularly in many low-to-middle income countries. Malaria caused by Plasmodium remains responsible for some of the highest numbers of annual deaths of any human pathogen, whilst piroplasmids, such as Babesia and Theileria can have immense negative economic effects through livestock loss. Diagnosing haemoparasites via traditional methods like microscopy is challenging due to low-level and transient parasitaemia. PCR-based diagnostics overcome these limitations by being both highly sensitive and specific, but they may be unable to accurately detect coinfections or identify novel species. In contrast, next-generation sequencing (NGS)-based methods can characterize all pathogens from a group of interest concurrently, although, the short-read platforms previously used have been limited in the taxonomic resolution achievable. Here, we used Oxford Nanopore Technologies' (ONT) long-read MinION™ sequencer to conduct apicomplexan haemoparasite metabarcoding via sequencing the near full-length 18S ribosomal RNA gene, demonstrating its ability to detect Babesia, Hepatozoon, Neospora, Plasmodium, Theileria and Toxoplasma species. This method was tested on blood-extracted DNA from 100 dogs and the results benchmarked against qPCR and Illumina-based metabarcoding. For two common haemoparasites, nanopore sequencing performed as well as qPCR (kappa agreement statistics > 0.98), whilst also detecting one pathogen, Hepatozoon felis, missed by the other techniques. The long-reads obtained by nanopore sequencing provide an improved species-level taxonomic resolution whilst the method's broad applicability mean it can be used to explore apicomplexan communities from diverse mammalian hosts, on a portable sequencer that easily permits adaptation to field use.

BACKGROUND: Gestational trophoblastic disease (GTD) is an uncommon but highly treatable condition. There is limited local evidence to guide therapy. AIMS: To report the experience of a statewide registry in the treatment of low-risk gestational trophoblastic neoplasia (GTN) over a 20-year period. MATERIALS AND METHODS: A retrospective review of the prospectively maintained GTD registry database was conducted. There were 144 patients identified with low-risk GTN, of which 115 were analysed. Patient demographics, treatment details and outcomes, including development of resistance, toxicity or relapse were reviewed. RESULTS: The incidence of GTD was 2.6/1000 live births. There was 100% survival. The mean time from diagnosis to commencing treatment was 1.9 days (range 0-29 days). Seventy-seven percent of patients treated with methotrexate achieved complete response. Thirteen patients (11.3%) required multi-agent chemotherapy, for the treatment of resistant or relapsed disease. There was a higher rate of treatment resistance in those with World Health Organization (WHO) risk scores 5-6 (odds ratio (OR) 6.56, 95% CI 1.73-24.27, P = 0.005) and those with pre-treatment human chorionic gonadotropin >10 000 (OR 4.00 95% CI 1.73-24.27 P = 0.007). Four patients (3.5%) were diagnosed with choriocarcinoma after commencing treatment. Nine patients (7.8%) had successful surgical treatment for GTN, both alone and in combination with chemotherapy. The relapse rate was 4.3%; all were treated successfully with a combination of chemotherapy and surgery, and 93.9% of patients completed follow up through the registry. CONCLUSIONS: Methotrexate is a highly effective treatment for low-risk GTN, especially with WHO risk score ≤4. The optimal treatment for those with risk scores of 5-6 requires further investigation.

BACKGROUND: In spite of infants and children aged 0-5 years experiencing mental health difficulties being estimated to be in the range of 6%-18% globally, the mental health care needs for this age group are often overlooked in the design of specialist mental health services. Although there is increasing recognition of the importance of infant mental health services and treatments for younger children, access remains a barrier. Mental health services specifically designed for children 0-5 years are vital; however, little is known about how these services ensure access for infants at risk of mental health difficulties and their families. This scoping review seeks to address this knowledge gap. METHODS: A scoping review methodology framework was used to search for relevant articles published between January 2000 and July 2021, identified using five databases: MEDLINE, CINAHL, PsycINFO, SocIndex and Web of Science. The selection of studies was based on empirical research about access to infant mental health services and models of care. A total of 28 relevant articles met the eligibility criteria for inclusion in this review. RESULTS: Findings can be summarised under five broad themes: (1) accessibility for at-risk populations (2) the importance of early detection of infants in need of mental health services and interventions; (3) the promotion of culturally responsive services and interventions; (4) ensuring the sustainability of IMH services and programs and (5) the integration of innovative interventions to improve existing practice models. CONCLUSIONS: The findings from this scoping review highlight barriers to access and provision of infant mental health services. Future infant mental health service design, informed by research, is needed to improve access for infants and young children with mental health difficulties and their families.

Pathogenic variants in DDX3X are associated with neurodevelopmental disorders. Communication impairments are commonly reported, yet specific speech and language diagnoses have not been delineated, preventing prognostic counseling and targeted therapies. Here, we characterized speech and language in 38 female individuals, aged 1.69-24.34 years, with pathogenic and likely pathogenic DDX3X variants (missense, n = 13; nonsense, n = 12; frameshift, n = 7; splice site, n = 3; synonymous, n = 2; deletion, n = 1). Standardized speech, language, motor, social, and adaptive behavior assessments were administered. All participants had gross motor deficits in infancy (34/34), and fine motor deficits were common throughout childhood (94%; 32/34). Intellectual disability was reported in 86% (24/28) of participants over 4 years of age. Expressive, receptive, and social communication skills were, on average, severely impaired. However, receptive language was significantly stronger than expressive language ability. Over half of the assessed participants were minimally verbal (66%; 22/33; range = 2 years 2 months-24 years 4 months; mean = 8 years; SD = 6 years) and augmented speech with sign language, gestures, or digital devices. A quarter of the cohort had childhood apraxia of speech (25%; 9/36). Despite speech and language impairments, social motivation was a relevant strength. Many participants used augmentative and alternative communication (AAC), underscoring the need for early, tailored, and comprehensive AAC intervention.

The human immune system is best accessible via tissues and organs not requiring major surgical intervention, such as blood. In many circumstances, circulating immune cells correlate with an individual's health state and give insight into physiological and pathophysiological processes. Stimulating whole blood ex vivo is a powerful tool to investigate immune responses. In the context of clinical research, the applications of whole blood stimulation include host immunity, disease characterization, diagnosis, treatment, and drug development. Here, we summarize different setups and readouts of whole blood assays and discuss applications for preclinical research and clinical practice. Finally, we propose combining whole blood stimulation with high-throughput technologies, such as single-cell RNA-sequencing, to comprehensively analyze the human immune system for the identification of biomarkers, therapeutic interventions as well as companion diagnostics.