Uncinate fasciculus microstructural organisation and emotion recognition in schizophrenia: controlling for hit rate bias.

Introduction: Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i.e., participant guessing) during an emotion recognition task (ERT). Methods: Fifty-eight individuals diagnosed with SCZ were included. The CANTAB ERT was used to measure social cognition. Specific ROI manual tract segmentation was completed using ExploreDTI and followed the protocol previously outlined by Coad et al. (2020). Results: We found that the microstructural organisation of the UF was significantly correlated with physical neglect and ER outcomes. Furthermore, we found that the UHR score was more sensitive to ERT subscale emotion items than the standard HR score. Finally, given the association between childhood trauma (in particular childhood neglect) and social cognition in SCZ, a mediation analysis found evidence that microstructural alterations of the UF mediated an association between childhood trauma and social cognitive performance. Discussion: The mediating role of microstructural alterations in the UF on the association between childhood trauma and social cognitive performance suggests that early life adversity impacts both brain development and social cognitive outcomes for people with SCZ. Limitations of the present study include the restricted ability of the tensor model to correctly assess multi-directionality at regions where fibre populations intersect.

The COVID-19 lockdown experience suggests that restricting the supply of gambling can reduce gambling problems: An Australian prospective study.

Background and aims: COVID-19 lockdowns limited access to gambling but simultaneously elevated psychosocial stressors. This study assessed the relative effects of these changes on gambling risk status during and after the Australian COVID-19 lockdown from late-March to late-May 2020. Methods: The study administered three surveys to people who had gambled within the past year at T1. Wave 1 asked about before (T1, N = 2,125) and during lockdown (T2, N = 2,125). Subsequent surveys focused on one year (T3; N = 649) and two years after lockdown (T4, N = 458). The dependent variable was changes in reporting any problem gambling symptoms (PGSI 0 vs 1+). Bivariate analyses and multinomial logistic regression tested for significant associations with: demographics, psychosocial stressors (perceived stress, psychological distress, loneliness, health anxiety about COVID, financial hardship, stressful life events), gambling participation and gambling frequency. Results: Gambling participation and at-risk gambling decreased between T1 and T2, increased at T3, with little further change at T4. When gambling availability was curtailed, decreased gambling frequency on EGMs, casino games, sports betting or race betting, and lower psychosocial stress, were associated with transitions from at-risk to non-problem gambling. When gambling availability resumed, increased EGM gambling frequency, decreased online gambling frequency, and higher psychosocial stress were associated with transitions from non-problem to at-risk gambling. Discussion and conclusions: Gambling availability appears a stronger influence on gambling problems, at the population level, than psychosocial risk factors. Reducing the supply of high-risk gambling products, particularly EGMs, is likely to reduce gambling harm.

Improving the quality of antenatal screening and early intervention for alcohol and other drug use: protocol for a multi-stage approach to systems reform.

BACKGROUND: Alcohol, tobacco and illicit drug use during pregnancy can cause significant harm to women and their developing fetuses. Despite recommendations for abstinence during pregnancy, some women continue to use, making screening for substance use during antenatal clinic attendances an important strategy for reducing risk. This study aims to improve the rates of screening and intervention for substance use among pregnant women, including appropriate referral for those who may be substance-dependent. The protocol outlined here focuses on a multi-stage implementation study. METHODS: This study will occur in four phases. Phase 1 will identify a baseline rate of screening and subsequent care at the antenatal clinics of two, South Australian hospital-based maternity services, through a retrospective case note audit. Rates of self-reported substance use identified in the case notes will also be compared against representative data from Adelaide Primary Health Network to establish rates of over or underreporting. Phase 2 will involve an online Training Needs Analysis of midwifery staff working at those services, to assess their knowledge, attitudes, beliefs, and commitment to the care of women who use substances during pregnancy. Phase 3 will involve a training package for all midwifery staff at those services, focused on routine screening for substance use, and how to provide appropriate care. Outcome measures from phase 2 will be reassessed during phase 3 and any changes since training will be evaluated. Phase 4 will then repeat phase 1 to compare the changes in rates of both screening and any associated intervention before and after training. DISCUSSION: From a public health perspective, this project has the potential to make a significant impact on reducing risk of harm from substance use disorders among pregnant women, and contribute to better health outcomes for their children. TRIAL REGISTRATION:  This trial has been pre-registered under the Open Science Framework. REGISTRATION: https://doi.org/10.17605/OSF.IO/73FDZ .

Metrological traceability in flow cytometry? Evaluation of a new volumetric method for lymphocyte subsets.

INTRODUCTION: Lymphocyte subset enumeration by flow cytometry is important for the therapeutic monitoring of a range of conditions. However, current bead-based methodologies do not produce metrologically traceable results. Here we compare an established bead-based methodology with a volumetric-based system traceable to an internationally recognised reference method. METHOD: A total of 118 samples received for lymphocyte subset analysis were tested using an established bead-based technique (BD Multitest™ 6-colour TBNK assay using Trucount™ tubes on a BD FACSLyric flow cytometer), followed by a volumetric method on the Sysmex XF-1600 flow cytometer using Exbio Kombitest 6-colour TBNK reagent. All samples were tested in accordance with the manufacturer's instructions. RESULTS: Absolute count values from both methodologies for CD3+, CD3 + CD4+, CD3 + CD8+, CD19+ and CD3-CD16+/CD56+ lymphocyte populations were compared using linear regression (R2 for all parameters >0.95) and Bland-Altman analysis. There was no significant bias (where p < 0.05) for absolute CD3 + CD4+ lymphocytes in the defined therapeutic range of 0-250 cells/µL (mean bias: 0.27 cells/µL). Although positive biases were seen for CD3 + CD4+ lymphocytes (over the entire range tested: 14-1798 cells/µL) and CD3-CD16+/CD56+ lymphocytes (mean bias: 10.83 cells/µL and 6.79 cells/µL, respectively). Negative biases were seen for CD3 + CD8+ and CD19+ lymphocytes (mean bias: -29.17 cells/µL and - 18.76 cells/µL, respectively). CONCLUSION: A high degree of correlation was found for results from both methodologies and observed bias was within the limits of clinical acceptability for all populations. This shows that the metrologically traceable lymphocyte subset absolute counts produced by the Sysmex XF-1600 are robust within clinically required limits.

Building workforce capacity to address substance use in primary health care: preliminary results from a mixed-methods pilot program.

BACKGROUND: Primary health care is critical to the prevention of alcohol, tobacco and other drug-related harms. Scaling-up screening, brief intervention and referral to treatment (SBIRT) within primary health care can reduce the burden of substance-related diseases, and improve downstream healthcare services. Building knowledge, skills and confidence among general practitioners (GPs), particularly in rural, regional and remote areas, to deliver SBIRT is an essential step. Therefore, this study aimed to pilot test a skills-based training program for GPs designed to build capacity for SBIRT delivery. METHODS: This pilot study investigated the acceptability of a structured, educational skills-based training program among GPs, as well as its preliminary effectiveness in inducing changes in confidence to deliver SBIRT, and in increasing knowledge about low-risk alcohol guidance. The training package was designed by experts in addiction medicine and public health, and involved a series of online webinars and in-person workshops at four locations across the South Eastern NSW Primary Healthcare Network catchment. RESULTS: A total of 18 GPs registered for the training, with six completing the final webinar. The GPs who completed all sessions demonstrated increases in confidence to deliver SBIRT and alcohol guidance knowledge from baseline. Qualitative feedback found the program acceptable, and GPs were able to successfully implement learnings into practice, and promote to colleagues. CONCLUSIONS: The results indicated the potential of this program at a national level, but highlighted the need for a range of additional incentives to encourage uptake and ongoing implementation.

Electronic gaming machine accessibility and gambling problems: A natural policy experiment.

Background: Electronic gaming machines (EGMs) are one of the most harmful forms of gambling at an individual level. It is unclear whether restriction of EGM functions and accessibility results in meaningful reductions in population-level gambling harm. Methods: A natural policy experiment using a large (N = 15,000) national dataset weighted to standard population variables was employed to compare estimates of gambling problems between Australian residents in Western Australia (WA), where EGMs are restricted to one venue and have different structural features, to residents in other Australian jurisdictions where EGMs are widely accessible in casinos, hotels and clubs. Accessibility of other gambling forms is similar across jurisdictions. Results: Gambling participation was higher in WA, but EGM participation was approximately half that of the rest of Australia. Aggregate gambling problems and harm were about one-third lower in WA, and self-reported attribution of harm from EGMs by gamblers and affected others was 2.7× and 4× lower, respectively. Mediation analyses found that less frequent EGM use in WA accounted for the vast majority of the discrepancy in gambling problems (indirect path = -0.055, 95% CI -0.071; -0.038). Moderation analyses found that EGMs are the form most strongly associated with problems, and the strength of this relationship did not differ significantly across jurisdictions. Discussion: Lower harm from gambling in WA is attributable to restricted accessibility of EGMs, rather than different structural features. There appears to be little transfer of problems to other gambling forms. These results suggest that restricting the accessibility of EGMs substantially reduces gambling harm.

Ward-level leadership quality and prospective low-back pain of eldercare workers: do resident handlings mediate the association?

OBJECTIVE: We investigated the extent to which ward-level leadership quality was associated with prospective low-back pain among eldercare workers, and how this association was mediated by observed resident handlings. METHODS: 530 Danish eldercare workers, employed in 121 wards, distributed across 20 nursing homes were evaluated. At baseline, leadership quality was measured using the Copenhagen Psychosocial Questionnaire, and resident handlings [handlings per shift, handlings not using assistive devices, handlings done alone, interruptions to handlings, impediments to handlings] were assessed using observations. Frequency and intensity of low-back pain was assessed monthly during the following year. All variables were averaged for each ward. We used ordinary least squares regressions to examine direct effects of leadership on low-back pain and indirect effects through handlings, using PROCESS-macro for SPSS. RESULTS: After adjustments for low-back pain at baseline, type of ward, staff ratio (i.e., number of workers divided by number of residents) and proportion of devices not in place, leadership quality showed no effect on prospective low-back pain frequency (ß = 0.01 [- 0.05:0.07]) and a small beneficial effect on pain intensity (ß = - 0.02 [- 0.04:0.00]). Resident handlings did not mediate the association between leadership quality and frequency or intensity of low-back pain. CONCLUSIONS: Good leadership quality was associated with a small decrease in prospective low-back pain intensity, but resident handlings did not seem to play a mediating role, although better ward-level leadership quality contributed to fewer workplace-observed resident handlings without assistance. Potentially, organizational factors, such as type of ward and staff ratio, may have a greater influence on handlings and low-back pain than leadership quality per se among eldercare workers.

A Blueprint for the Stabilization of Sub-Valent Alkaline Earth Complexes.

The study of sub-valent Group 2 chemistry is a relatively new research field, being established in 2007 with the report of the first Mg(I) dimers. These species are stabilized by the formation of a Mg-Mg covalent bond; however, the extension of this chemistry to heavier alkaline earth (AE) metals has been frustrated by significant synthetic challenges, primarily associated with the instability of heavy AE-AE interactions. Here we present a new blueprint for the stabilization of heavy AE(I) complexes, based upon the reduction of AE(II) precursors with planar coordination geometries. We report the synthesis and structural characterisation of homoleptic trigonal planar AE(II) complexes of the monodentate amides {N(SiMe3 )2 }- and {N(Mes)(SiMe3 )}- . DFT calculations showed that the LUMOs of these complexes all show some d-character for AE = Ca-Ba. DFT analysis of the square planar Sr(II) complex [Sr{N(SiMe3 )2 }(dioxane)2 ]∞ revealed analogous frontier orbital d-character. AE(I) complexes that could be accessed by reduction of these AE(II) precursors were modelled computationally, revealing exergonic formation in all cases. Crucially, NBO calculations show that some d-character is preserved in the SOMO of theoretical AE(I) products upon reduction, showing that d-orbitals could play a crucial role in achieving stable heavy AE(I) complexes.

Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer.

BACKGROUND: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the HPV genotypes and HPV16 variants in biopsies from women ≤ 25 years of age with cervical carcinoma (CC) (cases), compared with those aged >25 years (controls), in a pre-vaccination cohort. METHODS: HPV genotyping of archival paraffin blocks (n = 96) was performed using the INNO-LiPA HPV Genotyping assay. HPV16-positive samples were analysed for variants by type-specific PCR spanning L1, E2 and E6 regions. RESULTS: HPV16 was the commonest genotype in cases (54.5%, 12/22) and controls (66.7%, 46/69) (p = 0.30), followed by HPV18 (36.3%, 8/22 vs. 17.3% 12/69, respectively) (p = 0.08). Furthermore, 90% (20/22) of cases and 84.1% (58/69) of controls were positive for HPV16 or 18 (p = 0.42); 100% (22/22) of cases and 95.7% (66/69) of controls had at least one genotype targeted by the nonavalent vaccine (p = 0.3). The majority of HPV16 variants (87.3%, 48/55) were of European lineage. The proportion of unique nucleotide substitutions was significantly higher in cases (83.3%, 10/12) compared with controls (34.1%, 15/44), (p < 0.003, χ2, OR 9.7, 95%CI 1.7-97.7). CONCLUSIONS: Virological factors may account for the differences in CCs observed in younger compared with older women. All CCs in young women in this study had preventable 9vHPV types, which is important messaging for health provider adherence to new cervical screening guidelines.

Unambiguous evidence that over half of gambling problems in Australia are caused by electronic gambling machines: Results from a large-scale composite population study.

Background and aims: It is well understood that engagement with some forms of gambling, like EGMs, is riskier than other forms. However, while reports of associations are common, few studies have attempted to evaluate and compare the relative risk of all available forms, and none have estimated the relative contribution of each form to the total burden of gambling problems (GP) in a population. Methods: Using an aggregated dataset of national and state-based prevalence studies in Australia (N = 71,103), we estimated prevalence and unique effects of frequency of engagement on each form on GP. Two alternative numerical methods were then applied to infer the relative contribution of each form to the total amount of GP. Results: EGMs are responsible for 51%-57% of gambling problems in Australia, and 90% of gambling problems are attributable to EGMs, casino, race, and sports betting. Casino table games and EGMs are equally risky at the individual level, but the former contribute far less to problems due to low participation. Bingo and lottery play show no statistically detectable risk for GP. Discussion and conclusion: The results illustrate which forms present the greatest population burden and illuminate the reasons why. EGMs have an outsized impact. EGM uniquely combines high risk conditional on play, with a high participation rate and a high frequency of play among participants. This is in contrast to risky but less commonly played casino games, and prevalent but non-risky forms like lotteries. We conclude that EGM regulation should be a primary focus of policy action in Australia. More innovative policy ideas relating to EGMs should be tested due to the disproportionate impact of this product type.

Separating problem gambling behaviors and negative consequences: Examining the factor structure of the PGSI.

There is some uncertainty on how to best conceptualise and measure problem gambling and debate as to whether it is helpful to differentiate the behavioral features of problematic gambling from the negative consequences of gambling. The current study explores this issue by examining the factor structure of a commonly-used problem gambling measure, the Problem Gambling Severity Index (PGSI), as administered to respondents in the 2018 Northern Territory Gambling Prevalence and Wellbeing Survey (n = 3,740 gamblers). Confirmatory factor analyses revealed a two-factor solution offered significant improvement in fit over the one-factor model. Further, the two factors explained unique variance in the number of gambling-related harms experienced by respondents. Although the two factors were highly correlated, the current findings indicate problem gambling behaviors are related to the negative consequences of gambling, but these are not necessarily synonymous. This suggests isolating behavioral and consequential elements of gambling may have utility in public health interventions for gambling that, while concerning, falls below a clinically-significant threshold. Similarly, clinically-oriented research may benefit by measuring the behavioral features, as these components are important targets for individual-level interventions.

Brazilian version of need for recovery scale: Assessment of structural validity, criterion validity, and internal consistency.

BACKGROUND: The Need For Recovery scale (NFR) is a tool that allows early identification of work-related health risks. However, the structure of the Brazilian version of NFR scale (Br-NFR) which contains 11 items has not been evaluated. OBJECTIVES: To evaluate the structural validity, criterion validity, and internal consistency of the Br-NFR scale in workers. METHODS: 672 workers were included in this study. A split-half validation method was applied to the sample to create a development and validation sample. The structure of the Br-NFR was examined through Exploratory Factor Analysis (EFA) using the development sample. The validation sample was used to evaluate the structure with Confirmatory Factor Analysis (CFA). For the latter, several goodness-of-fit indices were considered to evaluate the model fit of the structures tested in this study. Criterion validity was assessed between the Brazilian structure and structures found in the literature compared with the original scale through intraclass correlation coefficient (ICC2,1). The internal consistency of the Br-NFR was assessed using Cronbach's alpha. Both analyses used the validation sample. RESULTS: The EFA showed that the scale has a one-factor structure and the CFA demonstrated that the Br-NFR structure with 7 items presented excellent to acceptable goodness-of-fit indices. Excellent values of ICC were found between the structures tested in the study and the original 11-item structure of the NFR. The Br-NFR scale presented good internal consistency. CONCLUSION: The Br-NFR is unidimensional. The final 7-item version presented to be equivalent to the original 11-item scale and also has good internal consistency.

A Simple Resident Need-for-Physical-Assistance Scale in Eldercare: Validation Using 4716 Observation Sequences of Caring Activities.

Accurate and simple measures for classifying nursing home residents according to their care needs would be valuable for planning eldercare work. Our aim was to validate a developed classification scale of residents' need for physical assistance. Eldercare workers and managers in 20 Danish nursing homes classified 1456 residents into four categories (from light to complete need for physical assistance). We validated the resident need-for-assistance scale against 4716 workplace observation sequences of caring activities performed by eldercare workers. We found a strong correlation between the resident need-for-assistance scale and observed number of resident handlings (r = 0.71) and a moderate correlation for observed duration of care (r = 0.57). The discriminative ability of the scale was good for both number of resident handlings (ROC-AUC = 0.81) and for duration of care (ROC-AUC = 0.76). Our findings indicate that this simple scale is valid and feasible for classifying residents according to their physical assistance needs.

Synthesis, characterisation and reactivity of group 2 complexes with a thiopyridyl scorpionate ligand.

Herein we report the reactivity of the proligand tris(2-pyridylthio)methane (HTptm) with various Alkaline Earth (AE) reagents: (1) dialkylmagnesium reagents and (2) AE bis-amides (AE = Mg-Ba). Heteroleptic complexes of general formulae [Mg(Tptm)(R)] (R = Me, nBu; Tptm = {C(S-C5H4N)3}-) and [AE(Tptm)(N'')] (AE = Mg-Ba; N'' = {N(SiMe3)2}-) were targeted from the reaction of HTptm with R2Mg or [AE(N'')2]2. Reaction of the proligand with dialkylmagnesium reagents led to formation of [{Mg(κ3C,N,N-C{Bu}{S-C5H4N}2)(µ-S-C5H4N)}2] (1) and [{Mg(κ3C,N,N-C{Me}{S-C5H4N}2)(µ-OSiMe3)}2] (2) respectively, as a result of a novel transfer of an alkyl group onto the methanide carbon with concomitant C-S bond cleavage. However, reactivity of bis-amide precursors for Mg and Ca did afford the target species [AE(Tptm)(N'')] (3-AE; AE = Mg-Ca), although these proved susceptible to ligand degradation processes. DFT calculations show that alkyl transfer in the putative [Mg(Tptm)(nBu)] (1m') system and amide transfer in 3-Ca is a facile process that induces C-S bond cleavage in the Tptm ligand. 3-Mg and 3-Ca were also tested as catalysts for the hydrophosphination of selected alkenes and alkynes, including the first example of mono-hydrophosphination of 4-ethynylpyridine which was achieved with high conversions and excellent regio- and stereochemical control.

Substance use in the emergency department: Screening for risky drug use, using the ASSIST-Lite.

INTRODUCTION: Substance use is a common contributing factor to emergency department (ED) presentations. While screening, brief intervention, and referral to treatment for alcohol and tobacco is common in ED settings, it is not routinely conducted for illicit substances. This study aimed to deploy the ASSIST-Lite to screen for risky use of alcohol and other drugs in the ED, to identify differences in risk based on between demographic characteristics. METHOD: All ED attenders, aged 18 years or older, deemed well enough to participate were approached. Recruitment occurred at the Royal Adelaide Hospital ED between May and June 2017. Participants were asked to self-complete the ASSIST-Lite in the ED waiting room. Overall, 632 people were approached, of which 479 (75.8%) agreed to participate. RESULTS: Alcohol (72.2%), tobacco (27.1%) and cannabis (15.2%) were most commonly reported. Eighty-nine participants reported moderate- or high-risk use of two substances, and a further 49 individuals reported moderate- or high-risk use of three or more substances. Across most substances, age, gender and employment status was associated with risky substance use, with higher likelihood of risk reported by males, unemployed and younger participants. Unemployment was also significantly associated with increased risk severity for both moderate and high-risk illicit use. DISCUSSIONS AND CONCLUSIONS: The rate of risky illicit and polysubstance use found here highlight the need more focused research in ED settings. The findings also provide support for more routine screening, and early intervention approaches; and suggest the need for active referral pathways through an alcohol and other drug consultation liaison service.

Gambling-related harms to concerned significant others: A national Australian prevalence study.

Background and aims: Gambling-related harm to concerned significant others (CSOs) is an important public health issue since it reduces CSOs' health and wellbeing in numerous life domains. This study aimed to 1) estimate the first national prevalence of CSOs harmed by gambling in Australia; 2) identify the characteristics of CSOs most at risk of harm from another person's gambling; 3) compare the types and number of harms experienced by CSOs based on their relationship to the person who gambles; and 4) compare the number of harms experienced by CSOs by self-identified gender. Methods: Based on a national CATI survey weighted to population norms, 11,560 respondents reported whether they had been personally and negatively affected by another person's gambling in the past 12 months; and if so, answered detailed questions about the harms experienced from the person's gambling who had harmed them the most. Results: Past-year prevalence of gambling-related harm to adult Australian CSOs was (6.0%; 95% CI 5.6%-6.5%). CSOs most commonly reported emotional harms, followed by relationship, financial, health and vocational harms, respectively. Former partners reported the most harm, followed by current partners, other family members and non-family members, respectively. Female CSOs were more likely to report more harm and being harmed by a partner or other family member, and male CSOs from a non-family member. Discussion and conclusions: The findings provide new insights into the wider societal burden of gambling and inform measures aimed at reducing harm to CSOs from gambling and supporting them to seek help.

Structural Investigation of Magnesium Complexes Supported by a Thiopyridyl Scorpionate Ligand.

Herein, we report the synthesis of a series of heteroleptic magnesium complexes stabilized with the scorpionate ligand tris(2-pyridylthio)methanide (Tptm). The compounds of the general formula [Mg(Tptm)(X)] (1-X; X = Cl, Br, I) were obtained via protonolysis reaction between the proligand and selected Grignard reagents. Attempts to isolate the potassium derivative K(Tptm) lead to decomposition of Tptm and formation of the alkene (C5H4N-S)2C=C(C5H4N-S)2, and this degradation was also modelled using DFT methods. Compound 1-I was treated with K(CH2Ph), affording the degradation product [Mg(Bptm)2] (2; Bptm = {CH(S-C5NH3)2}-). We analyzed and quantified the steric properties of the Tptm ligand using the structural information of the compounds obtained in this study paired with buried volume calculations, also adding the structural data of HTptm and its CF3-substituted congener (HTptmCF3). These studies highlight the highly flexible nature of this ligand scaffold and its ability to stabilize various coordination motifs and geometries, which is a highly desirable feature in the design of novel organometallic reagents and catalysts.