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This article examines the reception history of the story of the woman with a flow of blood as recounted in Mark 5:25–34, Matthew 9:20–22, and Luke 8:43–48 within the writings of two late antique poets: Jacob of Serugh (ca. 451–521 CE) and Romanos Melodos (b. ca. 485 CE). In their poetic compositions, Jacob and Romanos retell and interpret biblical stories employing narrative expansions and the attribution of imagined speech. The Syriac poet, Jacob of Serugh, wrote in the form of narrative poems, or mēmrē, while Romanos perfected the form of the Greek kontakion. Like prose homilies, these poems reached Christians from across the social spectrum, providing spiritual instruction and delighting audiences. Previous reception histories of this biblical narrative have largely overlooked late antique and early Byzantine poetry performed within the liturgical space. In addition to filling this lacuna in scholarship, this article also highlights how these understudied poems contribute to our understanding of early Christian discourses of (im)purity. Romanos emphasizes the symbolic value of the gendered body, blending the imagery of stain, impurity, and sin. In contrast, Jacob’s lexical choices and poetic style underscore the woman’s physical and emotional strife. Through speech and the description of the woman’s bodily state, both poets provide dramatic depictions of the woman’s encounter with Jesus that enrich our understanding of how late antique Christians interpreted this biblical story.

The advanced form of AMD, geographic atrophy, is associated with increased RPE oxidative stress and chronic inflammation. Here we evaluated the effects of delivering an anti-inflammatory viral gene by an AAV-vector in a mouse model of geographic atrophy. We measured changes in retinal function, structure, and morphology over nine months with electroretinography, optical coherence tomography, and fundoscopy, respectively. In addition, we used retinal tissue to quantify changes in markers of inflammation by multiplex ELISA, RT-qPCR, and immunofluorescence staining. Our AAV significantly delayed the loss of retinal function and structure and decreased retinal inflammation compared to the control AAV treatment. Our results suggest that modulating retinal inflammation could significantly slow the progression of geographic atrophy.

Infant breastfeeding diagnostics remain subjective due to the absence of instrumentation to objectively measure and understand infant oral motor skills and suckling characteristics. Qualitative diagnostic exams, such as the digital suck assessment which relies upon a clinician’s gloved finger inserted into the infant’s mouth, produce a diversity of diagnoses and intervention pathways due to their subjective nature. In this paper, we report on the design of a non-nutritive suckling (NNS) system which quantifies and analyzes quantitative intraoral vacuum and sucking patterns of full-term neonates in real time. In our study, we evaluate thirty neonate suckling profiles to demonstrate the technical and clinical feasibility of the system. We successfully extract the mean suck vacuum, maximum suck vacuum, frequency, burst duration, number of sucks per burst, number of sucks per minute, and number of bursts per minute. In addition, we highlight the discovery of three intraoral vacuum profile shapes that are found to be correlated to different levels of suckling characteristics. These results establish a framework for future studies to evaluate oromotor dysfunction that affect the appearance of these signals based on established normal profiles. Ultimately, with the ability to easily and quickly capture intraoral vacuum data, clinicians can more accurately perform suckling assessments to provide timely intervention and assist mothers and infants towards successful breastfeeding outcomes.

Mental ill health is a major health risk for young people. There is unmet need for mental health assessment and treatment across Australia despite significant investment in government-funded plans to cover mental health and youth-oriented services. Understandings of mental health care for young people are impeded by a lack of longitudinal research. Without this research, it is difficult to understand how services do or do not support the recovery of young people over time.This project will analyse the healthcare journeys of young people aged 16-25 years experiencing their first significant episode of mental ill health, over 12 months in the Australian Capital Territory. The study team will recruit up to 25 diverse young people and their general practitioners (GPs), and conduct four qualitative semi-structured interviews over 12 months with each participant. GP interviews will explore their role in the mental health care and care coordination for the young person. Interviews with young people will explore experiences and perceptions of navigating the health system, and the supports and resources they engaged with during the 12-month period. In between interviews, young people will be asked to keep a record of their mental health care experiences, through their choice of media. Participant-produced materials will also form the basis for interviews, providing stimuli to discuss the lived experience of care.Through analysing the narratives of both young people and their GPs, the study will establish how young people understand value in mental health care delivery. The study will use longitudinal qualitative mapping of healthcare journeys to identify key barriers and enablers to establishing effective, person-centred health care for young people with mental ill health.

The Escherichia coli dnaE gene encodes the α‐catalytic subunit (pol IIIα) of DNA polymerase III, the cell’s main replicase. Like all high‐fidelity DNA polymerases, pol III possesses stringent base and sugar discrimination. The latter is mediated by a so‐called “steric gate” residue in the active site of the polymerase that physically clashes with the 2′‐OH of an incoming ribonucleotide. Our structural modeling data suggest that H760 is the steric gate residue in E.coli pol IIIα. To understand how H760 and the adjacent S759 residue help maintain genome stability, we generated DNA fragments in which the codons for H760 or S759 were systematically changed to the other nineteen naturally occurring amino acids and attempted to clone them into a plasmid expressing pol III core (α‐θ‐ε subunits). Of the possible 38 mutants, only nine were successfully sub‐cloned: three with substitutions at H760 and 6 with substitutions at S759. Three of the plasmid‐encoded alleles, S759C, S759N, and S759T, exhibited mild to moderate mutator activity and were moved onto the chromosome for further characterization. These studies revealed altered phenotypes regarding deoxyribonucleotide base selectivity and ribonucleotide discrimination. We believe that these are the first dnaE mutants with such phenotypes to be reported in the literature., The accurate replication of every living organisms’ genome is achieved by high fidelity DNA polymerases. The enzymes not only need to choose the nucleotide with the correctly paired base (G, A, T or C), but also the right sugar (deoxyribonucleotide, not ribonucleotide). We report here, the construction and characterization of three novel active site mutants of the α‐catalytic subunit of Escherichia coli DNA polymerase III that have altered phenotypes with regard to base and sugar discrimination.

Visuals are often used to enhance learning of scientific information. The recent emergence and popularity of comic-style instruction books for adults, such as the ‘manga guide to …’, shows the possibility of comic style visualisations for the communication of science with adults. This study investigates whether the addition and style of visual accompaniment of scientific information, as used in comic books, influences immediate and short-term fact recall in an adult audience. Participants ( n = 310 aged 18–79, 52% identified as female) were presented 20 general science facts in one of five styles: (1) text alone, (2) photo with text caption, (3) cartoon with text caption, (4) photo with explanatory agent and a speech bubble, (5) cartoon with explanatory agent and a speech bubble. Immediate recall, and confidence in that recall, was tested following a brief distractor. Participants indicated their preferred presentation style, and short-term recall was tested by a final quiz of all 20 facts. Overall, the most preferred presentation style was cartoon with explanatory agent and text in a speech bubble (26% preferred). There was no single most effective presentation style; there was no significant difference in immediate recall, short term recall or confidence in answers depending on whether the fact was presented as text, photo or cartoon, or the presence or absence of an explanatory agent. However, immediate recall was significantly better when preference was met ( p

Ageing is a global concern with major social, health, and economic implications. While individual countries seek to develop responses to immediate, pressing needs, international attention and collaboration is required to most effectively address the multifaceted challenges and opportunities an ageing global population presents in the longer term. The Ageing, Longevity and Health stream of the International Alliance of Research Universities (IARU-ALH) was built on a solid foundation of first-class interdisciplinary research and on innovative outreach and communication centres. This interdisciplinary network conducts projects that span biology, medicine, social sciences, epidemiology, public health, policy, and demography, and actively engages with the public and other societal stakeholders. Here we posit that such international interdisciplinary networks are needed and uniquely placed to address major challenges related to health and ageing and ultimately will produce new understanding and knowledge to promote the awareness of healthy ageing and encourage societal change via novel, science-informed interventions. Global interdisciplinary research presents great potential and opportunities to accelerate our understanding of human ageing and to produce new, more effective solutions to a pressing, complex problem. However, more focused, strategic efforts and investments are required in order to deliver on these potentials and reap maximum benefits for individuals and societies. IARU-ALH members are determined to contribute, in collaboration with others, to delivering on this vision.

The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.

Type 2 diabetes mellitus (T2D) prevalence continues to increase, and age of incidence continues to decrease. More information is needed to target interventions to the ages where they can be most effective. The objective of this study was to explore the degree to which the association between diet and T2D incidence changes through adulthood. Participants were a large number (N = 2818) of community living adults in Canberra and Queanbeyan, Australia across three cohorts; young (20–24 followed to 32–36), mid-life (40–44 followed to 52–56) and late-life (60–64 followed to 72–76). Self-report dietary pattern scores at baseline and diabetes incidence across 12 years follow-up were measured, alongside confounders of caloric intake, sex, smoking status, years of education, hypertension, BMI and physical activity. Cox proportional hazards indicated that neither Western nor Prudent dietary pattern scores were significantly associated with T2D incidence when confounders were included in the model. Unadjusted estimates suggested a positive association between Western dietary pattern scores and subsequent diabetes incidence (HR = 1.40, 95% CI [1.18, 1.64]). Compared with the mid-life cohort, a higher Western dietary pattern score posed a lower risk for incident T2D in the young cohort (unadjusted HR = 0.46, 95% CI [0.22, 0.96]), who also had significantly lower BMI and higher physical activity. No such significant effects were found for the late-life cohort. Our findings indicate that mid-life may be a period of heightened vulnerability to the effects of an unhealthy diet on diabetes risk, but this effect is attenuated when risk factors related to diet, such as adiposity, are taken into account.

Background Health experts including planners and policy-makers face complex decisions in diverse and constantly changing healthcare systems. Visual analytics may play a critical role in supporting analysis of complex healthcare data and decision-making. The purpose of this study was to examine the real-world experience that experts in mental healthcare planning have with visual analytics tools, investigate how well current visualisation techniques meet their needs, and suggest priorities for the future development of visual analytics tools of practical benefit to mental healthcare policy and decision-making. Methods Health expert experience was assessed by an online exploratory survey consisting of a mix of multiple choice and open-ended questions. Health experts were sampled from an international pool of policy-makers, health agency directors, and researchers with extensive and direct experience of using visual analytics tools for complex mental healthcare systems planning. We invited them to the survey, and the experts’ responses were analysed using statistical and text mining approaches. Results The forty respondents who took part in the study recognised the complexity of healthcare systems data, but had most experience with and preference for relatively simple and familiar visualisations such as bar charts, scatter plots, and geographical maps. Sixty-five percent rated visual analytics as important to their field for evidence-informed decision-making processes. Fifty-five percent indicated that more advanced visual analytics tools were needed for their data analysis, and 67.5% stated their willingness to learn new tools. This was reflected in text mining and qualitative synthesis of open-ended responses. Conclusions This exploratory research provides readers with the first self-report insight into expert experience with visual analytics in mental healthcare systems research and policy. In spite of the awareness of their importance for complex healthcare planning, the majority of experts use simple, readily available visualisation tools. We conclude that co-creation and co-development strategies will be required to support advanced visual analytics tools and skills, which will become essential in the future of healthcare. Graphical abstract

Previous studies examining the neural substrates of reward processing in ASD have explored responses to rewards for oneself but not rewards earned for others (i.e., vicarious reward). This omission is notable given that vicarious reward processing is a critical component of creating and maintaining social relationships. The current study examined the neural mechanisms of vicarious reward processing in 15 adults with ASD and 15 age- and gender-matched typically developing controls. Individuals with ASD demonstrated attenuated activation of reward-related regions during vicarious reward processing. Altered connectivity was also observed in individuals with ASD during reward receipt. These findings of altered neural sensitivity to vicarious reward processing may represent a mechanism that hinders the development of social abilities in ASD.

Autism spectrum disorder (ASD) is characterized by impaired predictive abilities; however, the neural mechanisms subsuming reward prediction errors in ASD are poorly understood. In the current study, we investigated neural responses during social and nonsocial reward prediction errors in 22 adolescents with ASD (ages 12-17) and 20 typically developing control adolescents (ages 12-18). Participants performed a reward prediction error task using both social (i.e., faces) and nonsocial (i.e., objects) rewards during a functional magnetic resonance imaging scan. Reward prediction errors were defined in two ways: (a) the signed prediction error, the difference between the experienced and expected reward; and (b) the thresholded unsigned prediction error, the difference between expected and unexpected outcomes regardless of magnitude. During social reward prediction errors, the ASD group demonstrated the following differences relative to the TD group: (a) signed prediction error: decreased activation in the right precentral gyrus and increased activation in the right frontal pole; and (b) thresholded unsigned prediction error: increased activation in the right anterior cingulate gyrus and bilateral precentral gyrus. Groups did not differ in brain activation during nonsocial reward prediction errors. Within the ASD group, exploratory analyses revealed that reaction times and social-communication impairments were related to precentral gyrus activation during social prediction errors. These findings elucidate the neural mechanisms of social reward prediction errors in ASD and suggest that ASD is characterized by greater neural atypicalities during social, relative to nonsocial, reward prediction errors in ASD. Autism Res 2020, 13: 715-728. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We used brain imaging to evaluate differences in brain activation in adolescents with autism while they performed tasks that involved learning about social and nonsocial information. We found no differences in brain responses during the nonsocial condition, but differences during the social condition of the learning task. This study provides evidence that autism may involve different patterns of brain activation when learning about social information.

The availability of healthcare data has exponentially grown, both in quantity and complexity. The speed of this evolution has generated new challenges for translating complex data into effective evidence-informed policy. Visual analytics offers new capacity to analyze healthcare systems and support better decision-making. We conducted a systematic scoping review to look for evidence of visual analytics approaches being applied to mental healthcare systems and their use in driving policy. We found 79 relevant studies and categorized them in two ways: by study purpose and by type of visualization. The majority (67.1%) of the studies used geographical maps, and 11% conducted highly complex studies requiring novel visualizations. Significantly, only 15% of the studies provided information indicating high levels of usability for policy and planning. Our findings suggest that while visual analytics continues to evolve rapidly, there is a need to ensure this evolution reflects the practical needs of policy makers.

BackgroundChronic stress alters reward sensitivity and contributes to the emergence of anhedonia. In clinical samples, the perception of stress is a strong predictor of anhedonia. While there is substantial evidence demonstrating psychotherapy reduces perceived stress, little is known regarding the effects of treatment-related decreases in perceived stress on anhedonia.MethodsThe current study investigated reciprocal relations between perceived stress and anhedonia using a cross-lagged panel model approach in a 15-week clinical trial examining the effects of Behavioral Activation Treatment for Anhedonia (BATA), a novel psychotherapy to treat anhedonia, compared to a Mindfulness-Based Cognitive Therapy (MBCT) comparison intervention (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136).ResultsTreatment completers (n=72) experienced significant reductions in anhedonia (M=-8.94, SD=5.66) on the Snaith-Hamilton Pleasure Scale (t(71)=13.39, pM=-3.71, SD=3.88) on the Perceived Stress Scale (t(71)=8.11, pn=87), a longitudinal autoregressive cross-lagged model revealed significant paths showing that higher levels of perceived stress at treatment Week 1 predicted reductions in anhedonia at treatment Week 4.ConclusionsLongitudinal models illustrated that individuals with relatively high perceived stress at the start of treatment were likely to report relatively lower anhedonia a few weeks into treatment. At mid-treatment, individuals with low perceived stress were more likely to report lower anhedonia towards the end of treatment. Early treatment components are thought to reduce perceived stress, allowing for mid-to-late treatment components to exert their direct effects on anhedonia. The findings presented here demonstrate the importance of including stress-reducing components in cognitive-behavioral-based anhedonia treatments.

With advancements in the pharmaceutical industry pushing more towards tailored medicines, novel approaches to tablet manufacture are in high demand. One of the main drivers towards micro-scale batch production is the ability to fine-tune drug release. This study demonstrates the use of rapid tooling injection moulding (RTIM) for tablet manufacture. Tablets were manufactured with varying structural features to alter the surface area whilst maintaining the same volume, resulting in differing specific surface area (SSA). The precision of this technique is evaluated based on eleven polymer formulations, with the tablets displaying < 2% variability in mass. Further tablets were produced containing paracetamol in three different polymer-based formulations to investigate the impact of SSA on the drug release. Significant differences were observed between the formulations based on the polymers polyvinyl alcohol (PVA) and Klucel ELF. The polymer base of the formulation was found to be critical to the sensitivity of the drug release profile to SSA modification. The drug release profile within each formulation was modified by the addition of structural features to increase the SSA.

There is a growing body of evidence surrounding the implications of uncontrolled bushfires and wildfires on water. This topic has importance from an ecological perspective, and significance for human health as it has consequences for drinking water quality and supply. Against the backdrop of climate change, it is especially important to holistically understand the impact of fire on water. This review took a systematic approach to establish a comprehensive overview of the changes occurring in freshwater systems following uncontrolled wildfires and bushfires. Screening of 16,551 results obtained from Web of Science, PubMed, and MEDLINE resulted in 111 manuscripts suitable for inclusion. The impact of fire across a wide range of water quality indicators either relative to pre-fire measurements or reference sites was examined qualitatively (increase/decrease) and where possible quantitatively (% change or difference). Factors included biomass, indicator species and species diversity, metals, nutrients, salts, polycyclic aromatic hydrocarbons, particulates and turbidity, pH, conductivity, temperature, and water course morphology. Evidence focused largely on short to medium term impacts (e.g. within 2 years of the fire event), with only a subset of studies reporting on longer term changes in response to fire. We found that bushfire has acute and long-lasting effects on water in terms of physical (e.g. decreased suspended particle size), chemical (e.g. increased nutrient concentration), and biological (e.g. decreased species diversity) characteristics. There was also evidence of resilience and recovery. We urge future work to consider measures that will fulfil both environmental and human health considerations, to allow more integrated insight into the impacts of fire on water.

Moral injury (MI) research has been expanded to populations beyond the military in recent years. A key barrier to further research into MI in civilian populations is the lack of valid, reliable measures of the construct appropriate for general civilian use. This paper addresses this barrier by adapting two existing military measures, and exploring their psychometrics in a general civilian sample: The Moral Injury Events Scale (MIES-Civilian) and Expressions of Moral Injury Scale-Military (EMIS-Civilian). A sample of civilian women (n = 192) and men (n = 88) completed the above measures, and additional scales designed to capture theoretically-supported primary and secondary markers of MI (guilt, shame, anger; depression, post-traumatic stress symptoms, anxiety). Confirmatory factor analysis found that the factor structure of the MIES-C and EMIS-C replicated well within our civilian sample. Discriminant validity was indicated through significant negative correlation with wellbeing. Both measures correlated as predicted with each other and measures of MI markers at the total score level. Correlations of individual subscales with each of these measures were more varied, shedding light on differential relationships between type of MI event and clinical outcomes, and suggesting some conceptual differences in how MI is experienced in general civilian populations. Results suggest that civilian populations are also susceptible to MI, but that existing measures may have problems capturing this effectively. While the MIES-C and EMIS-C are supported for civilian use, further scale construction efforts for this population are warranted.

Objective: To quantify the association between blood pressure (BP) across its full range and brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), antihypertensive medication, and other risk factors. Methods: UK Biobank participants ( N =36,260) aged 40 to 70 years were included and stratified by sex and age into four groups (age ≤ 45, 46-55, 56-65 and > 65 years old). Multi-level regression analyses were used to assess the association between mean arterial (MAP), systolic (SBP), and diastolic (DBP) blood pressure, and brain volumes segmented using the FreeSufer software (gray matter [GMV], white matter [WMV], left [L] and right hippocampal volume [RHCV]) and WMLs. We also investigated the interaction effects between body mass index (BMI) and antihypertensive medication and BP in predicting brain volumes and WMLs. Results: Every 10-mmHg higher DBP was associated with lower brain volumes (GMV: -1300– -2800) [SE=34–90]; WMV: -903.44– -1171.7[SE=34.66–53.03]; LHCV: -7.7– -14.26 [SE=0.44–0.57]; RHCV: -6.25– -22.64[SE=0.32–0.95]) across all age groups. A similar pattern was detected in both sexes, although it was weaker, in men. Also, every 10-mmHg higher MAP was associated with larger WMLs across all age groups but peaked > 65 years (0.1 [SE=0.002]). Both lower BMI and anti-hypertensive medication appeared to afford a protective effect. Conclusion: Higher BP is associated with worse cerebral health across the full BP range from middle adulthood and across the life course. Therefore, it is important that prevention efforts be directed at younger adults with focus on achieving optimal BP to decrease future risk of developing dementia.

A key question for the design of clinical trials for Alzheimer's disease (AD) is whether the timing of conversion from mild cognitive impairment (MCI) to AD can be predicted. This is also an important question for the clinical management of MCI. This study aims to address this question by exploring the contribution of baseline brain volume and annual volume change, using Cox regression, in predicting the time to conversion. Individuals with MCI, who converted to AD (n = 198), reverted to normal (n = 38), or remained stable (n = 96) for at least five years, were included in this study. The results revealed that the volumes of all the brain areas considered were predictive of the time to conversion from MCI to AD. Annual change in volume was also predictive of the time to conversion but only when initial volumes were above a certain threshold. This is important because it suggests that reduction in atrophy rate, which is the outcome of some clinical trials, is not inevitably associated with delay in conversion from MCI to AD.

Objectives The aim of the study was to determine lipid profile differences between premenopausal and postmenopausal women. Methods The present review used a meta-analytic approach. Sixty-six studies were included, which provided a total sample of 114,655 women consisting of 68,394 that were premenopausal and 46,261 that were postmenopausal. Results The main findings were that (1) lipoproteins were significantly higher in postmenopausal women compared to premenopausal women including triglycerides (0.27 mmol/L, 95% confidence interval, 0.22-0.31), total cholesterol (0.58, 0.50-0.65), low-density lipoprotein (0.45, 0.38-0.53), and total cholesterol to high-density lipoprotein levels (0.39, 0.16-0.62); (2) there was no difference in high-density lipoprotein levels between premenopausal and postmenopausal women (0.02, -0.00-0.04); and (3) the differences in lipid levels was partly attributable to the mean age difference between premenopausal and postmenopausal women. Conclusions These findings are important as they provide precise estimates of lipid differences in women around menopause. Furthermore the results suggest that the unfavorable lipid profile that develops in postmenopausal women puts them at higher risk of cardiovascular disease such as heart disease and stroke if appropriate lifestyle/pharmacological interventions are not implemented.

Age-related macular degeneration (AMD) has been linked to oxidative damage and para-inflammation, an activation of inflammasome signaling in the retinal pigment epithelium (RPE) and the underlying choriocapillaris. Herein, we tested the efficacy of a gene-delivered caspase-1 inhibitor in controlling the retinal degeneration observed in two models of RPE-choroid oxidative damage. In an acute model of oxidative stress (NaIO3 injection), eyes pre-treated with the sGFP-TatCARD (trans-activator of transcription; caspase activation and recruitment domain) vector demonstrated a recovery of retinal function and partial protection of RPE structure 1 month after damage, in contrast with control-treated eyes. In a model of chronic oxidative stress (RPE-specific deletion of Sod2), eyes treated with the sGFP-TatCARD vector after the onset of degeneration had a significantly slower decline in retinal function when compared to control-treated eyes. Earlier treatment of this model with the same adeno-associated virus (AAV) vector resulted in a greater protection of RPE function in eyes treated with the TatCARD when compared to control-treated eyes. Our results demonstrate that intravitreal delivery of sGFP-TatCARD reduces inflammation and can protect the retina from both acute and sustained oxidative damage within the RPE and choroid. Therefore, gene therapy with a cell-penetrating inflammasome inhibitor such as CARD may stem the progression of AMD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major disease burden which accounts for 5% of all deaths globally, with most of those (>90%) occurring in lower to middle income countries (LMIC). It is also emerging as an important modifiable dementia risk factor.OBJECTIVE: To address the knowledge gap surrounding the nature of the associations between COPD, dementia, and mortality, and the geographical variation of those associations in LMIC.METHODS: Data from the 10/66 study surveying 15,394 participants (mean age 74 years, 62% female) across 8 countries was used to estimate the prevalence of self-reported COPD and its association with incident dementia and premature death. Proportional sub-hazards models using a cumulative incidence function were applied to identify the probability of incident dementia onset given the risk of premature death, with estimates pooled across countries via random effect meta-analysis.RESULTS: Over the 3-year follow-up, almost 10% of participants developed dementia and 14% were deceased. COPD was not significantly associated with dementia incidence except in Cuba. However, fully adjusted models indicated that individuals with COPD were at a 28% increased risk of premature death, a trend present across most countries when analyzed individually.CONCLUSION: The link between COPD and dementia is currently somewhat different and weaker in LMIC than in developed countries. This may be because premature death in the populations studied mask the development of clinical dementia. Given the global trend toward increased life expectancy, it is critical that the disease burden associated with COPD be addressed without delay if a further rise in dementia prevalence associated with COPD is to be avoided in LMIC.

Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).

Background Local shape complexity can be biologically meaningful as a marker of disease, trauma, or change in brain structure over time. Fractal dimensionality (FD) is currently the dominant measure of local shape complexity used in neuroimaging but its limitations are not well understood. New method Elliptical Fourier harmonic power requirement (HPR) may provide complementary information to FD. We benchmarked the performance of FD and HPR on a series of simulated shapes, systematically manipulating aspects of local shape complexity, and a series of clinical contours (glioma tumour cores and stroke lesions from the BRATS and ATLAS datasets). HPR was calculated as the point of 99.9% harmonic power. FD was calculated at six resolutions (8 × 8, 16 × 16, 32 × 32, 64 × 64, 128 × 128, and 256 × 256), by using an approach which computationally indexes the complexity of the shape boundary (i.e. the number of cells defining the contour) relative to the total grid size. Results and comparison with existing methods PR and FD were moderately positively correlated ( r ≈ 0.2 to 0.8 depending on shape properties), and both were sensitive to the frequency and amplitude of local complexity. FD was most biased by rotation, while HPR was more biased by global shape features such as deep invaginations. FD indicated an aggregate measure of complexity across the whole contour, while HPR indicated the point of highest complexity. Conclusions The HPR index provides conceptually distinct local complexity information from the current FD standard. Future research will benefit from using these complementary measures.

Abstract. The ubiquity of mobile telephones worldwide offers a unique opportunity for bidirectional communication between researchers and participants. There are two ways mobile phones could be used to collect self-report data: via Short Message Service (SMS) or app (mobile telephone software applications). This study examined the comparative data quality offered by SMS and app, when mobile phone type, self-report instrument, and sampling schedule are controlled. One hundred ten undergraduate students used their own iPhones to complete the same repeated measures instrument on 20 occasions, responding either by SMS or by app. There were no differences between SMS and app respondents in terms of response rates or response delay. However, data from those responding via SMS was significantly less complete than from app respondents. App respondents rated their respondent experience as more convenient than SMS respondents. Though findings are only generalizable to an undergraduate sample, this suggests that researchers should consider using apps rather than SMS for repeated measures self-report data collection.

Background Neurobiological predictors of antidepressant response may help guide treatment selection and improve response rates to available treatments for major depressive disorder (MDD). Behavioral activation therapy for depression (BATD) is an evidence-based intervention designed to ameliorate core symptoms of MDD by promoting sustained engagement with value-guided, positively-reinforcing activities. The present study examined pre-treatment task-based functional brain connectivity as a predictor of antidepressant response to BATD. Methods Thirty-three outpatients with MDD and 20 nondepressed controls completed a positive emotion regulation task during fMRI after which participants with MDD received up to 15 sessions of BATD. We used generalized psychophysiological interaction analyses to examine group differences in pre-treatment functional brain connectivity during intentional upregulation of positive emotion to positive images. Hierarchical linear models were used to examine whether group differences in functional connectivity predicted changes in depression and anhedonia over the course of BATD. Results Compared to controls, participants with MDD exhibited decreased connectivity between the left middle frontal gyrus and right temporoparietal regions during upregulation of positive emotion. Within the MDD group, decreased connectivity of these regions predicted greater declines in anhedonia symptoms over treatment. Limitations Future studies should include comparison treatments and longitudinal follow-up to clarify the unique effects of BATD on neural function and antidepressant response. Conclusions Results are consistent with previous work showing BATD may be particularly effective for individuals with greater disturbances in brain reward network function, but extend these findings to highlight the importance of frontotemporoparietal connectivity in targeting symptoms of low motivation and engagement.

Background The COVID-19 outbreak has spread to almost every country around the world and caused more than 3 million deaths. The pandemic has triggered enormous disruption in people’s daily lives with profound impacts globally. This has also been the case in Australia, despite the country’s comparative low mortality and physical morbidity due to the virus. This scoping review aims to provide a broad summary of the research activity focused on mental health during the first 10 months of the pandemic in Australia. Results A search of the Australian literature was conducted between August-November 2020 to capture published scientific papers, online reports and pre-prints, as well as gaps in research activities. The search identified 228 unique records in total. Twelve general population and 30 subpopulation group studies were included in the review. Conclusions Few studies were able to confidently report changes in mental health driven by the COVID-19 context (at the population or sub-group level) due to a lack of pre-COVID comparative data and non-representative sampling. Never-the-less, in aggregate, the findings show an increase in poor mental health over the early period of 2020. Results suggest that young people, those with pre-existing mental health conditions, and the financially disadvantaged, experienced greater declines in mental health. The need for rapid research appears to have left some groups under-researched (e.g. Culturally and Linguistically Diverse populations and Indigenous peoples were not studied), and some research methods under-employed (e.g. there was a lack of qualitative and mixed-methods studies). There is a need for further reviews as the follow-up results of longitudinal studies emerge and understandings of the impact of the pandemic are refined.

The objectives of this study were to investigate the long-term associations between changes in physical activity levels and hippocampal volumes over time, while considering the influence of age, sex, and APOE-ε4 genotype. We investigated the effects of change in physical activity on hippocampal volumes in 411 middle age (mean age = 47.2 years) and 375 older age (mean age = 63.1 years) adults followed up to 12 years. An annual volume decrease was observed in the left (middle age: 0.46%; older age: 0.51%) but not in the right hippocampus. Each additional 10 metabolic equivalents (METs, ~2 h of moderate exercise) increase in weekly physical activity was associated with 0.33% larger hippocampal volume in middle age (equivalent to ~1 year of typical aging). In older age, each additional MET was associated with 0.05% larger hippocampal volume; however, the effects declined with time by 0.005% per year. For older age APOE-ε4 carriers, each additional MET was associated with a 0.10% increase in hippocampal volume. No sex effects of physical activity change were found. Increasing physical activity has long-term positive effects on hippocampal volumes and appears especially beneficial for older APOE-ε4 carriers. To optimize healthy brain aging, physical activity programs should focus on creating long-term exercise habits.

Background The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia. Methods We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses. Results : Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample. Conclusions : Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC.

The use of additive manufacturing techniques in conjunction with injection moulding is becoming increasingly popular, with financial and time benefits to coupling the techniques. This study demonstrates a systematic development process of 3D printed rapid tooled moulds using stereolithography. A high flexural modulus and elongation were found to increase the likelihood of success of a mould material in the injection moulding process. Success is defined as the mould surviving the process and being capable of producing the desired object successfully. Stereolithography was found to produce high quality moulds when a diagonal print orientation and a scaling factor of 109.3% is employed. The presented technique and systematic workflow is highly suitable for the production of moulds with detailed micro-features. This is of particular interest for rapid tooling for micro-injection moulding for the manufacture of pharmaceuticals and medical devices, where the microstructure directly impacts the performance of the products.