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The dysconnection hypothesis of schizophrenia posits that widespread synaptic inefficiencies lead to altered macroscale brain connectivity, contributing to symptom severity and cognitive deficits in individuals with schizophrenia spectrum disorders (SSD). Emerging evidence suggests that physical exercise may help to ameliorate these connectivity abnormalities and associated clinical impairments.
Aims
This study investigated whether reductions in functional dysconnectivity following exercise therapy were associated with clinical improvements in individuals with SSD. In addition, it explored the genetic underpinnings of these changes using imaging transcriptomics.
Method
Using data from the ESPRIT C3 trial, we analysed 23 SSD patients (seven female) undergoing aerobic exercise or flexibility, strengthening and balance training over 6 months. Functional dysconnectivity, assessed at baseline and post-intervention relative to a healthy reference sample (n = 200), was evaluated at the whole-brain, network and regional levels. Linear mixed effect models and voxel-wise Pearson’s correlations were used to assess exercise-induced changes and clinical relevance.
Results
Functional dysconnectivity significantly decreased (d = −2.73, P < 0.001), and this decrease was primarily linked to enhanced oligodendrocyte-related gene expression. Reductions in the default-mode network were correlated with improved global functioning, whereas changes in insular regions were associated with symptom severity and functioning. Dysconnectivity reductions in somatomotor and frontoparietal networks were correlated with total symptom improvements, and changes in language-related regions (e.g. Broca’s area) were linked to cognitive benefits.
Conclusions
Our findings support the role of oligodendrocyte pathology in SSD and suggest that targeting dysconnectivity in the default-mode, salience and language networks may enhance global functioning, symptom severity and cognitive impairments.
Mental health awareness efforts are increasing, especially for ADHD. There is growing evidence that such efforts may also cause unnecessary self-diagnosis and worsening symptoms for some disorders; however, there are no validated approaches to avoid these potential harms without reducing the awareness efforts themselves. We developed a multifaceted intervention, called nocebo education. The intervention was based on the principles of the nocebo effect, where negative expectations may cause symptom misattribution and worsening. We tested whether teaching about the nocebo effect could mitigate the potential false self-diagnosis and symptom worsening from ADHD awareness.
Methods
In a double-blind randomized controlled trial with a week-long follow-up (NCT06638411), 215 healthy young adults (77% women) were randomized to participate in a group workshop on either ADHD awareness, ADHD combined with nocebo education, or control (sleep). We measured changes in self-diagnosis and ADHD symptoms immediately after the workshop (self-diagnosis), and 1-week later (self-diagnosis and symptoms).
Results
ADHD group reported substantially higher self-diagnosis scores immediately $ ({\beta}_{\mathrm{standardised}}=0.80\;\left[0.58,1.02\right],p<.001 $) and 1 week after the workshop $ (\beta =0.50\;\left[0.28,0.72\right],p<.001 $) compared to controls. These effects persisted despite no changes in reported symptoms. Nocebo education halved the false self-diagnosis scores immediately after the workshop ($ \beta =0.45\;\left[0.23,0.67\right],p<.001 $) and eliminated the false self-diagnosis entirely at follow-up $ (\beta =0.16\;\left[-0.06,0.38\right],p=.08 $).
Conclusions
We show that being exposed to ADHD awareness reliably increases false self-diagnosis among healthy young adults for at least one week; a brief nocebo education intervention is efficacious in substantially reducing and later eliminating it. Nocebo education is a promising adjunct for balanced awareness efforts that could be applied in various contexts.
The Northeast Greenland Ice Stream (NEGIS) is an elongated feature extending ∼600 km into the interior of the Greenland Ice Sheet. Here, we investigate detailed subglacial topography along the length of the NEGIS to ascertain the characteristics of the ice stream bed. We use topographic analysis (hypsometry, spatial roughness and valley morphometry) to describe and demarcate three geomorphologically distinct regions. The upstream region, near the NEGIS onset, exhibits low roughness and a lack of valleys, indicating the likely presence of subglacial sediments. Downstream, roughness abruptly increases, with two wide subglacial troughs present in the middle region. In the downstream region, the topography displays smaller alpine-like valleys. We propose that these differences are attributable to changing geological provinces, which are poorly constrained in this area. The topography also has a distinct impact on ice stream geometry, as ice flow is generally preferentially steered through a trough. Whilst the upstream regime appears to have little effect on the location of the ice stream onset and shear margins, its low friction enables fast flow that propagates longitudinally upstream from the troughs. On the basis of our data, we argue that the NEGIS is more strongly influenced by basal topography than has been previously suggested.
We present a theoretical study, supported by simulations and experiments, on the spreading of a silicone oil drop under MHz-frequency surface acoustic wave (SAW) excitation in the underlying solid substrate. Our time-dependent theoretical model uses the long-wave approach and considers interactions between fluid dynamics and acoustic driving. While similar methods have analysed the micron-scale oil and water film dynamics under SAW excitation, acoustic forcing was linked to boundary layer flow, specifically Schlichting and Rayleigh streaming, and acoustic radiation pressure. For the macroscopic drops in this study, acoustic forcing arises from Reynolds stress variations in the liquid due to changes in the intensity of the acoustic field leaking from the SAW beneath the drop and the viscous dissipation of the leaked wave. Contributions from Schlichting and Rayleigh streaming are negligible in this case. Both experiments and simulations show that, after an initial phase where the oil drop deforms to accommodate acoustic stress, it accelerates, achieving nearly constant speed over time, leaving a thin wetting layer. Our model indicates that the steady speed of the drop results from the quasi-steady shape of its body. The drop speed depends on drop size and SAW intensity. Its steady shape and speed are further clarified by a simplified travelling-wave-type model that highlights various physical effects. Although the agreement between experiment and theory on drop speed is qualitative, the results’ trend regarding SAW amplitude variations suggests that the model realistically incorporates the primary physical effects driving drop dynamics.
Turbulent wall-bounded flows, although present in many practical applications, are particularly challenging to simulate because of their large velocity gradients near the walls. To avoid the necessity of an extremely fine mesh resolution in the near-wall regions of wall-bounded turbulent flows, large eddy simulation (LES) with specific modelling near the wall can be applied. Since filtering close to the boundaries of the flow domain is not uniquely defined, existing wall-modelled LES typically rely on extensive assumptions to derive suitable boundary conditions at the walls, such as assuming that the instantaneous filtered velocity behaves similarly to the unfiltered mean velocity. Volume filtering constitutes a consistent extension of filtering close to the boundaries of the flow domain. In the present paper, we derive a formally exact expression for the wall-boundary conditions in LESs using the concept of volume filtering applied to wall-bounded turbulent flows that does not make any a priori assumptions on the flow field. The proposed expression is an infinite series expansion in powers of the filter width. It is shown in an a priori study of a turbulent channel flow and an a posteriori study of the turbulent flow over periodic hills that the proposed expression can accurately predict the volume-filtered velocity at the wall by truncating the infinite series expansion after a few terms.
Research on the dissent–repression nexus assumes that repression of non-violent protesters undermines popular support for the regime. We challenge this assumption, arguing that coercion does not automatically generate legitimacy costs as bystanders’ pre-existing beliefs about targeted socio-political groups condition how repression is evaluated. While we expect bystanders to disapprove of and sanction repression of liked protester groups, we hypothesize that they will approve of and perhaps even credit the regime for repressing groups they do not sympathize with. We probe these hypotheses in a pre-registered survey experiment (with 3,569 Russian respondents), in which we pre-evaluate respondents’ beliefs about different socio-political groups in Russia and vary the participating group and the government’s response in a realistic protest vignette. The results corroborate our hypotheses and even show that the Russian president’s approval ratings are largely unaffected by regime coercion, indicating that autocrats have much more leeway in using repression than usually thought.
We review the state of the evidence for the existence and observational appearance of supermassive black hole binaries. Such objects are expected from standard hierarchical galaxy evolution to form after two galaxies, each containing a supermassive black hole, have merged, in the centre of the merger remnant. A complex interaction is predicted to take place with stars and gas in the host galaxy, leading to observable signatures in weakly as well as actively accreting phases. Direct observational evidence is available and shows examples of dual active galactic nuclei from kpc scales down to parsec scales. Signatures of possibly closer supermassive black hole binaries may be seen in jetted black holes. The interaction with stars and gas in a galaxy significantly affects the hardening of the binary and hence contributes to uncertainties of the expected gravitational wave signal. The Laser Interferometer Space Antenna (LISA) should in the future detect actual mergers. Before the launch of LISA, pulsar timing arrays may have the best chance to detect a gravitational wave signal from supermassive black hole binaries. The first signs of the combined background of inspiralling objects might have been seen already.
We consider the two-layer quasi-geostrophic model with linear bottom friction and, in certain simulations, a planetary vorticity gradient, $\beta$. We derive energy budgets in wavenumber space for eddy available potential energy (EAPE), baroclinic eddy kinetic energy (EKE) and barotropic EKE, a particular decomposition that has previously been overlooked. The conversion between EAPE and baroclinic EKE, $\widehat {T}^{{W}}$, has a strong dependence on both bottom drag strength and planetary $\beta$. At the deformation scale $\widehat {T}^{{W}}$ is always negative, representing the conversion of EAPE to EKE via baroclinic instability. For strong, linear bottom drag, $\widehat {T}^{{W}}$ is positive at large scales due to frictional energisation of the baroclinic mode, providing a large-scale EAPE source. With weak-to-moderate bottom drag and moderate-to-strong planetary $\beta$, $\widehat {T}^{{W}}$ is the dominant source of EAPE at large scales, converting baroclinic EKE that has experienced a baroclinic inverse cascade back into EAPE, and thus closing a novel and exclusively baroclinic energy loop. With planetary $\beta$, zonal jets form and the dominant large-scale processes in the energy cycle of the system, e.g. barotropic dissipation and the peak of positive $\widehat {T}^{{W}}$, occur at the meridional wavenumber corresponding to the jet spacing, with no zonal wavenumber component, i.e., $k_{x}=0$. Importantly, the traditional source of large-scale EAPE, barotropic stirring of the baroclinic mode, is not a part of this $k_{x} = 0$ energy cycle, and thus plays a secondary role. The results suggest that consideration of horizontally two-dimensional processes is requisite to understand the energetics and physics of baroclinic geophysical jets.
Continued global environmental degradation generates risks to human health, for example, through air pollution, disease, and food insecurity. This study focuses on these three types of health impact and explores what drives these risks. The risks can arise from diverse causes including political, economic, social, technological, legal/regulatory, and environmental factors. We assembled diverse experts to work together to produce ‘system maps’ for how risks arise, identifying monitoring ‘watchpoints’ to help track risks and interventions that can help prevent them materialising. We critically appraise this pilot methodology, in order to improve our capacity to understand and act to protect human health.
Technical summary
Systemic risks arise through a process of contagion across political, economic, social, technological, legal/regulatory, and environmental systems. The highly complex nature of these risks prevents probabilistic assessment as is carried out for more conventional risks. This study critically explores a new approach based on participatory systems mapping with experts from diverse backgrounds helping to appraise these risks and identify data and monitoring ‘watchpoints’ to track their progress. We focus on three case studies: air quality, biosecurity, and food security. We assembled 36 experts selected in a stratified way to maximise cognitive diversity, plus 14 members of the interdisciplinary project team. Across 7 workshops, we identified 39 ‘risk cascades’, defined as pathways by which systemic risk can have negative impacts on human health, and we identified 681 watchpoints and interventions. We identify a broad range of interventions to reduce risk, exploring systems approaches to help prioritise these interventions; for example, understanding co-benefits in terms of reducing multiple different types of risk, as well as trade-offs. In this paper, we take a reflective approach, critically discussing constraints and refinements to our pilot methodology, in order to enhance capacity to appraise and act on systemic risks.
Social media summary
How can we act on the risks from air pollution, disease, and food insecurity? Insights from a new systemic risk assessment methodology.
The lowest mass at which the third dredge-up (TDU) occurs for thermally pulsing asymptotic giant branch (TP-AGB) stars remains a key uncertainty in detailed stellar models. S-type AGB stars are an important constraint on this uncertainty as they have C/O ratios between 0.5 and 1, meaning they have only experienced up to a few episodes of TDU. AGB stars are also long-period variable stars, pulsating in low order radial pulsation modes. In this paper, we estimate the initial masses of a large sample of intrinsic S-type AGB stars, by analysing their visual light curves, estimating their luminosities with Gaia DR3 parallax distances and finally comparing to a grid of detailed stellar models combined with linear pulsation models. We find that the initial mass distribution of intrinsic S-type stars peaks at 1.3–1.4 M$_{\odot}$ depending on model assumptions. There also appear to be stars with initial masses down to 1 solar mass, which is in conflict with current detailed stellar models. Additionally, we find that though the mass estimates for semiregular variable stars pulsating in higher order radial modes are precise, the Mira variables pulsating in the fundamental mode present challenges observationally from uncertain parallax distances, and theoretically from the onset of increased mass-loss and the necessity of non-linear pulsation models.
Social media offers many benefits but also carries risks, including exposure to distressing content. The UK’s Online Safety Act requires certain platforms to empower users to control the content they see. Content controls can reduce users’ exposure to sensitive content. However, there is little public data on how platform design shapes the use of these controls. In our online randomised controlled trial on a simulated social media platform, participants were given an initial choice between seeing ‘All content types’ or ‘Reduced sensitive content’. After browsing, they were given the opportunity to change their choice. In the Control arm, none of the options were pre-selected. 24% chose ‘Reduced sensitive content’. Pre-selecting ‘All content types’ reduced this proportion to 15%. Conversely, adding a description of ‘sensitive content’ on the choice page increased that figure to 29%. The initial choice proved to be ‘sticky’. When invited to review after browsing, those defaulted away from ‘Reduced sensitive content’ did not switch any more than those whose choice was not influenced by a default. Overall, user choice was susceptible to choice architecture, and users’ tendency to update their initial choice was weak. This highlights the importance of platform design to deliver genuine user empowerment.
This quasi-experimental before-and-after intervention study evaluated an indication-based electronic prescribing alert in a 450-bed tertiary care hospital. Implementation reduced meropenem use by 41% without compromising patient safety, demonstrating the effectiveness of this targeted antimicrobial stewardship strategy.
Expanding public and policy maker knowledge, coupled with decisive action, is key to addressing antimicrobial resistance (AMR). These strategies provide a pathway to move beyond the AMR echo-chamber and drive meaningful change globally: (1) Improve knowledge translation, (2) Invest in public engagement, (3) Leverage One Health partners, and (4) Develop science-policy partnerships.
Stretching for 1.5km and consisting of approximately 5200 precisely aligned holes, Monte Sierpe in southern Peru is a remarkable construction that likely dates to at least the Late Intermediate Period (AD 1000–1400) and saw continued use by the Inca (AD 1400–1532). Yet its function remains uncertain. Here, the authors report on new analyses of drone imagery and sediment samples that reveal numerical patterns in layout, potential parallels with Inca knotted-string records and the presence of crops and wild plants. All this, the authors argue, suggests that Monte Sierpe functioned as a local, Indigenous system of accounting and exchange.
The history of legal aid in South Asia has hitherto been restricted to appendages or short overviews in writings orientated towards its contemporary. This article offers the first archivally grounded study of the birth of the legal aid movement in early twentieth-century colonial India, focusing specifically on the Bombay Legal Aid Society. It pursues three major lines of inquiry. First, I consider the transnational intellectual networks between India and America upon which early Indian legal aid thinking developed. Second, I tackle the fraught politics of doing legal aid in interwar Bombay, a period marked by anticolonial nationalism and strong trade union organizing. Finally, the article examines why the BLAS succeeded in building strong working relationships with existing social welfare societies, state institutions, and like-minded legal professionals, but failed to garner considerable interest from the working classes it sought to serve. I argue that these struggles point to the hard limits of legal aid in the colony but also present a valuable window into the Bombay working classes’ legal consciousness. The article thus contributes to ongoing efforts at globalizing the history of legal aid and to the small but growing study of the legal profession in colonial South Asia.
The COVID-19 pandemic triggered a deep economic crisis that prompted governments and central banks to implement extraordinary fiscal, monetary, and financial interventions. We examine public support for these interventions using a conjoint survey experiment conducted in Australia and the United Kingdom in early 2021. Our experiment innovates by investigating public preferences across two main categories of intervention: (1) wage subsidies designed to address employment and income risks and (2) financial stabilization measures aimed at supporting the balance sheets of households, businesses, and financial institutions. Results show that wagesubsidies received robust public support across diverse social, economic, and experiential cleavages. By contrast, financial and credit market interventions elicited mixed reactions, with strongest opposition toward those benefiting large firms and banks. We argue that the variation in support is primarily driven by an alignment of fairness considerations and policy design. In both countries, wage subsidies had key design features that made them more likely to be perceived as distributionally neutral, consistent with important fairness norms, and limiting the potential for free riding. They were available to all citizens experiencing verifiable employment disruption, delivered through employers, and appealed to welfare-chauvinistic views by excluding many recent immigrants and temporary residents. Moreover, the viral origin of the economic shock was widely perceived as exogenous and quasi-random, and the associated losses – particularly those related to employment and income more readily elicited greater empathy when borne by individuals than by firms. In contrast, financial-sector interventions, especially those aiding large corporations and banks, were less easily viewed as consistent with these fairness norms. These interventions were more prone to being perceived as favoring opportunistic or politically connected firms, echoing earlier public resentment of global financial crisis bailouts. Even some household-targeted financial interventions, such as debt relief and rent holidays, likely raised concerns among respondents about undeserved gains. Unlike some existing studies, our subgroup analysis finds little evidence that personal or local pandemic experiences significantly influenced attitudes toward economic interventions. Individuals who suffered direct health or economic impacts, or who lived in areas with high infection rates or strict lockdowns, were no more or less supportive of interventions. Instead, partisan orientation and perceptions of inequality were more predictive. Left-wing partisans and those who perceived rising or high inequality were especially supportive of wage subsidies and household-focused assistance. Traditional material cleavages – such as income, education, wealth, or asset ownership – had limited explanatory power. The underbanked population was an exception, showing more muted support for all interventions, likely due to perceived exclusion or limited personal benefit. We conclude that public evaluations of economic interventions during the pandemic were shaped less by self-interest or crisis exposure than by judgments about deservingness, fairness, and partisan attachments. Our findings emphasize the importance of policy design and political framing in sustaining public support for large-scale interventions during crises, and they have broader implications for the politics of economic policy in future global shocks.
Robust surfaces capable of reducing flow drag, controlling heat and mass transfer, and resisting fouling in fluid flows are important for various applications. In this context, textured surfaces impregnated with a liquid lubricant show promise due to their ability to sustain a liquid–liquid interface that induces slippage. However, theoretical and numerical studies suggest that the slippage can be compromised by surfactants in the overlying fluid, which contaminate the liquid–liquid interface and generate Marangoni stresses. In this study, we use Doppler-optical coherence tomography, an interferometric imaging technique, combined with numerical simulations to investigate how surfactants influence the slip length of lubricant-infused surfaces with longitudinal grooves in a laminar flow. Surfactants are endogenously present in the contrast agent (milk) which is added to the working fluid (water). Local measurements of slip length at the liquid–liquid interface are significantly smaller than theoretical predictions for clean interfaces (Schönecker & Hardt 2013). In contrast, measurements are in good agreement with numerical simulations of fully immobilized interfaces, indicating that milk surfactants adsorbed at the interface are responsible for the reduction in slippage. This work provides the first experimental evidence that liquid–liquid interfaces within textured surfaces can become immobilised in the presence of surfactants and flow.