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Statins are among the most prescribed medications worldwide. Both beneficial (e.g. antidepressant and pro-cognitive) and adverse (e.g. depressogenic and cognitive-impairing) mental health outcomes have been described in clinical studies. The underlying neuropsychological mechanisms, whether positive or negative, are, however, not established. Clarifying such activities has implications for the safe prescribing and repurposing potential of these drugs, especially in people with depression.
Methods
In this double-blind, randomized, placebo-controlled experimental medicine study, we investigated the effects of simvastatin on emotional processing, reward learning, working memory, and waking salivary cortisol (WSC) in 101 people at-risk for depression due to reported high loneliness scores (mean 7.3 ± 1.2 on the UCLA scale). This trial was largely conducted during periods of social distancing due to the COVID-19 pandemic (July 2021–February 2023), and we employed a fully remote design within a UK-wide sample.
Results
High retention rates, minimal outlier data, and typical main effects of task condition (e.g. emotion) were seen in all cognitive tasks, indicating this approach was comparable to in-person testing. After 28 days, we found no statistically significant differences (F’s < 3.0, p’s > 0.20) for any of the measures of emotional processing, reward learning, working memory, and WSC.
Conclusions
Study results do not substantiate concerns regarding adverse neuropsychiatric events due to statins and support the safety of their prescribing in at-risk populations. Although other unmeasured cognitive processes may be involved, our null findings are also in line with more recent clinical evidence suggesting statins do not show antidepressant or pro-cognitive efficacy.
My salary will be reduced 10% on April 1. Are students bitching about my lousy teaching? Have I been less productive on the research front? Less willing to shoulder my share of administrative burdens? All this could be true - or not - but has nothing to do with my pay cut. From slacker to Nobel Prize winner, every one of my colleagues at the University of Tsukuba is seeing his or her salary fall. As are all professors at all of Japan's national universities. And, indeed, everyone in Japan who is paid, directly or indirectly, by the Japanese tax payer - or, more precisely, paid by all the borrowing the Japanese government has been doing since taxes now cover less than half the Japanese government's expenses.
Grazing is a crucial component of dairy farms across many regions of the world. This review explores challenges related to grazing infrastructure and opportunities for future improvement. Farmers who aim to increase pasture utilisation face heightened inter-animal competition necessitated by pasture restriction to achieve target post-grazing sward heights. Increasing the frequency of fresh pasture allocation beyond once per day has been observed to reduce milk production in primiparous animals, due to intensified competition for limited feed resources. Implementing grazing paddocks tailored for 24- to 36-hour allocations helps to mitigate inter-animal competition while concurrently preventing the grazing of fresh regrowth. Crucial to this approach is establishing farm roadway infrastructure that allows access to all sections of the grazing platform. However, the development of these roadway networks has often occurred without a comprehensive assessment of their impact on the efficiency of the dairy herd’s movement between grazing paddocks and the milking parlour. The efficiency of the dairy herd’s movement is most significantly influenced by the location of the milking parlour within the grazing platform. Extreme walking distances or challenging terrain on farm roadways may have an impact on milk production per cow. Factors such as farm roadway surface quality and width significantly influence cow throughput on farm roadways. Recent studies have highlighted inadequate roadway widths on many farms relative to their herd size, while surface condition may also be limiting cow throughput on these farms. Enhancing roadway width and surface condition of farm roadways may improve labour efficiency on commercial farms.
Coastlines worldwide are coming under increasing pressure due to climate change and human activity. Data on shoreline change are essential for coastal managers and when no long-term monitoring programs are implemented and shoreline change is typically on the order of less than 1 m/yr., as observed in Ireland, aerial photography is the most valuable source of information. A well-established literature exists for automated vegetation extraction from digital images based on the near infrared reflectance, but there is less research available on spectrally limited colour photography. This study develops a methodology for automating vegetation line extraction from a series of historical aerial photography of the Cork coastline in the South-West of Ireland. The approach relies on the Normalised Green–Blue Difference Index (NGBDI), which is versatile enough to discriminate disparate coastal vegetation environments, at different resolutions and in various lighting and seasonal conditions. An iterative optimal threshold process and the use of LiDAR ancillary datasets resulted in an automated vegetation line measurement with uncertainties estimated to be between 0.6 and 1.2 m. Change rates derived from the vegetation lines extracted present uncertainties in the range of ±0.27 m/yr. This robust and repeatable method provides a valuable alternative to time-consuming and subjective manual digitisation.
Biodiversity is in rapid decline, but the extent of loss is not well resolved for poorly known groups. We estimate the number of extinctions for Australian non-marine invertebrates since the European colonisation of the continent. Our analyses use a range of approaches, incorporate stated uncertainties and recognise explicit caveats. We use plausible bounds for the number of species, two approaches for estimating extinction rate, and Monte Carlo simulations to select combinations of projected distributions from these variables. We conclude that 9,111 (plausible bounds of 1,465 to 56,828) Australian species have become extinct over this 236-year period. These estimates dwarf the number of formally recognised extinctions of Australian invertebrates (10 species) and of the single invertebrate species listed as extinct under Australian legislation. We predict that 39–148 species will become extinct in 2024. This is inconsistent with a recent pledge by the Australian government to prevent all extinctions. This high rate of loss is largely a consequence of pervasive taxonomic biases in community concern and conservation investment. Those characteristics also make it challenging to reduce that rate of loss, as there is uncertainty about which invertebrate species are at the most risk. We outline conservation responses to reduce the likelihood of further extinctions.
We investigated whether an observed reduction in overall childhood cancer risk (<15 years of age) in twins has been sustained, and how this extends into young adulthood. We searched for English language publications reporting childhood cancer risk in twins, obtained unpublished data directly from some authors, and updated a meta-analysis. We used the Swedish Multigeneration Register to investigate the age to which the reduced overall risk of childhood cancer (observed previously using that Swedish dataset and in this and earlier meta-analyses) persisted into the teenage/young adult years, and which specific tumors accounted for the overall risk reduction beyond childhood. Our meta-analysis of studies of aggregate childhood cancer risk in twins confirmed their approximate 15% reduction in cancer mortality and incidence. Further analysis of Swedish Multigeneration Register data for 1958 to 2002 suggested these reduced risks of cancer (particularly leukaemias and renal tumors) extended from childhood to young adult ages. Reduced risks of these and some other specific tumor types occurring across childhood/teenage/young adult years appeared to account for most of the overall risk reduction. Our results suggest a persistent reduction of overall childhood cancer risk in twins and that this extends into young adulthood. Risk reductions for several specific tumors might account for this and, although there are several potential explanations, intrauterine growth patterns of twins might be a major contributor.
The chronology of the Inka Empire is poorly resolved, with most scholars utilizing a post hoc ethnohistoric reconstruction of imperial expansion as a common reference point. Radiocarbon-based analyses can now accomplish sufficient resolution for meaningful independent estimates of Inka chronology, however, and it is incumbent upon archaeologists to develop such appraisals. Here we produce a Bayesian analysis of radiocarbon data from the Upper Loa River area of northern Chile to estimate the timing of Inka incorporation of this region. In order to accurately associate samples with Inka rule, only radiocarbon dates from Inka sites without prior occupations are used (n = 34), producing a model for the onset of Inka rule of AD 1401–1437 (95% hpd) with a median date of AD 1420. This estimate is further used as a point of comparison for understanding diachronic imperial processes in the region. Site-level models of a variety of site types indicate that the Inka rapidly founded several administrative/mining bases at the onset, followed by the addition of smaller infrastructure components during a second pulse of activity near the middle of the 15th century. Date assemblages at the agricultural sites of Topaín and Paniri also indicate a decline in activity at the former and an increase in activity at the latter from early on in Inka rule. These results provide a high-resolution data point for reconstructing Inka imperial chronology, and expanding such studies will be essential to understanding processes of Inka imperialism at larger scales.
We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window.
Methods:
Individual patients’ data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0–2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals.
Results:
608 patients were included. The median age was 70 years (IQR: 58–71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0–2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke.
Conclusion:
Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.
In pasture-based grazing systems, farm roadways are a pivotal link to connect paddocks on the grazing platform to the milking parlour. However, their effectiveness in the efficient movement of the dairy herd between the grazing paddocks and the milking parlour has yet to be fully quantified. A validation experiment was conducted on a research farm to analyse characteristics on farm roadways that may affect cow throughput, which was observed as the number of cows per minute (CPM) passing a specified location. Roadway width (R2 = 0.96) and surface condition score (SC) (R2 = 0.78, respectively) were both positively associated with CPM. Public road crossings imposed a 32.7% reduction in CPM in this study. CPM increased from 12.4 CPM on a one-metre-wide roadway with a SC of Index 1 to 107.6 CPM on a five-metre roadway with a SC of Index 5. This exercise allowed for CPM on commercial farms to be predicted. Farm roadways were examined across 55 Irish dairy farms. Greater roadway width, reduced verge width and greater water run-off were each associated with higher SC on commercial farms. Larger herd sizes had a lower CPM relative to herd size in contrast to smaller herd sizes, resulting in a significantly longer total time to move the dairy herd through any specific point on the farm roadway network. The findings from this study have quantified the parameters which affect both CPM on commercial farm roadways and parameters which may be associated with SC on commercial farm roadways.
Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.
Aims
Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Method
Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).
Results
Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.
Conclusions
Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
Offspring exposed to prenatal maternal depression (PMD) are vulnerable to depression across their lifespan. The underlying cause(s) for this elevated intergenerational risk is most likely complex. However, depression is underpinned by a dysfunctional frontal-limbic network, associated with core information processing biases (e.g. attending more to sad stimuli). Aberrations in this network might mediate transmission of this vulnerability in infants exposed to PMD. In this study, we aimed to explore the association between foetal exposure to PMD and frontal-limbic network function in infancy, hypothesising that, in response to emotional sounds, infants exposed to PMD would exhibit atypical activity in these regions, relative to those not exposed to PMD.
Method
We employed a novel functional magnetic resonance imaging sequence to compare brain function, whilst listening to emotional sounds, in 78 full-term infants (3–6 months of age) born to mothers with and without a diagnosis of PMD.
Results
After exclusion of 19 datasets due to infants waking up, or moving excessively, we report between-group brain activity differences, between 29 infants exposed to PMD and 29 infants not exposed to PMD, occurring in temporal, striatal, amygdala/parahippocampal and frontal regions (p < 0.005). The offspring exposed to PMD exhibited a relative increase in activation to sad sounds and reduced (or unchanged) activation to happy sounds in frontal-limbic clusters.
Conclusions
Findings of a differential response to positive and negative valanced sounds by 3–6 months of age may have significant implications for our understanding of neural mechanisms that underpin the increased risk for later-life depression in this population.
This chapter reviews the critical role that a contract research organization performs in developing new therapeutics for Alzheimer’s disease (AD). Late-phase AD trials are lengthy, expensive, and require specialized expertise and experience in order to optimize signal detection. We review the intricacies of AD protocol design, selection of optimal neuropsychiatric tests for different AD stages, rater training, imaging technologies, and use of biomarkers. Careful planning of trials involves well-thought-out investigator selection, site monitoring, and patient recruitment and retention strategies. Examples of operational issues in large global trials are also given, including adaptations necessary due to the COVID pandemic.
The prosecutorial independence of the Attorney General (AG) is a firmly established constitutional convention in Canada, but it is also an evolving convention, subject to ongoing contestation and debate. This article is a contribution to that debate. It defends a normative constitutional framework wherein the AG’s authority to make final decisions in matters of criminal prosecution is balanced against a corresponding duty to consult with cabinet and the prime minister on the public interest implications of prosecutorial decisions when the circumstances warrant. Within this normative framework, respectful contestation and debate amongst ministers, the prime minister, and the AG in determining the public interest merits of prosecution is welcomed, even encouraged, and if conducted with the requisite integrity, objectivity, and transparency, it is regarded not as a threat but as a valuable check and balance on AG independence and an indispensable form of quality control on the exercise of prosecutorial discretion.
Two introduced carnivores, the European red fox Vulpes vulpes and domestic cat Felis catus, have had extensive impacts on Australian biodiversity. In this study, we collate information on consumption of Australian birds by the fox, paralleling a recent study reporting on birds consumed by cats. We found records of consumption by foxes on 128 native bird species (18% of the non-vagrant bird fauna and 25% of those species within the fox’s range), a smaller tally than for cats (343 species, including 297 within the fox’s Australian range, a subset of that of the cat). Most (81%) bird species eaten by foxes are also eaten by cats, suggesting that predation impacts are compounded. As with consumption by cats, birds that nest or forage on the ground are most likely to be consumed by foxes. However, there is also some partitioning, with records of consumption by foxes but not cats for 25 bird species, indicating that impacts of the two predators may also be complementary. Bird species ≥3.4 kg were more likely to be eaten by foxes, and those <3.4 kg by cats. Our compilation provides an inventory and describes characteristics of Australian bird species known to be consumed by foxes, but we acknowledge that records of predation do not imply population-level impacts. Nonetheless, there is sufficient information from other studies to demonstrate that fox predation has significant impacts on the population viability of some Australian birds, especially larger birds, and those that nest or forage on the ground.
We revise Atkinson’s concept of a ‘participation income’ (PI), repositioning it as a form of green conditional basic income that is anchored in a capabilities-oriented eco-social policy framework. This framework combines the capability approach with an ‘ethics of care’ to re-shape the focus of social policy on individuals’ capability to ‘take care of the world’, thus shifting the emphasis from economic production to social reproduction and environmental reparation. In developing this proposal, we seek to address key questions about the feasibility of implementing PI schemes: including their administrative complexity and the criticism that a PI constitutes either an arbitrary and confusing, or invasive and stigmatising, form of basic income. To address these concerns, we argue for an enabling approach to incentivising participation whereby participation pathways are co-created with citizens on the basis of opportunities they recognise as meaningful rather than enforced through strict monitoring and sanctions.
The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to $\sim\!5$ yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of $\sim\!162$ h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of $0.24\ \mathrm{mJy\ beam}^{-1}$ and angular resolution of $12-20$ arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.
Contemporary models of welfare capitalism have frequently been critiqued about their fit-for-purpose in provisioning for people’s basic needs including care, and longer-term ecological sustainability. The Covid-19 pandemic has also exposed the need for better institutions and a new welfare architecture. We argue a post-productivist eco-social state can deliver sustainable well-being and meet basic needs. Arguing Universal Basic Services are an essential building block and prerequisite for a de-commodified welfare state, we focus on examining the form of income support that might best complement UBS. The article develops, from the perspective of feminist arguments and the capabilities approach, a case for Participation Income. This, we argue, can be aligned with targeted policy goals, particularly reward for and redistribution of human and ecological care or reproduction and other forms of socially valued participation. It may also, in the short term, be more administratively practical and politically feasible than universal basic income.