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Lurasidone is a second-generation antipsychotic with antidepressant properties, but its effect on depressive symptoms across diagnostic domains is not known.
Aims
This systematic review aims to synthesise the evidence for the transdiagnostic efficacy of lurasidone in reducing depressive symptoms.
Method
Electronic databases were searched up to October 2024 to identify randomised controlled trials comparing the effects of lurasidone and placebo on depressive symptoms, as measured by any standardised scale, in populations with different psychiatric diagnoses. Acceptability, tolerability and safety were also measured. The Cochrane risk of bias tool was used to assess study quality, and the GRADE tool to evaluate certainty of evidence. A random-effects meta-analysis was performed to estimate standardised mean differences (SMDs, for continuous outcomes) or relative risks (for dichotomous outcomes) with 95% CI.
Results
Fourteen trials met inclusion criteria. Pooled analysis of 5239 participants found lurasidone to be more efficacious than placebo in improving depression scores (SMD −0.26, 95% CI −0.37, −0.15) across multiple diagnoses (including schizophrenia, bipolar disorder and major depressive disorder). Secondary analyses showed better acceptability (relative risk 0.55, 95% CI 0.43, 0.71) and safety (relative risk 0.73, 95% CI 0.58, 0.91) and comparable tolerability (relative risk 0.74, 95% CI 0.54, 1.02) between lurasidone and placebo. The main limitations were the high risk of bias of several included studies and the high heterogeneity observed in our findings.
Conclusion
Lurasidone is a potentially efficacious and safe strategy for reducing depressive symptomatology across a range of psychiatric diagnoses. Further long-term, robust trials employing precision psychiatry methods are needed to support its broader use to target depressive symptoms transdiagnostically.
Cette étude propose une relecture inédite de la physique élémentaire d’Averroès à partir de trois questions laissées ouvertes par les textes d’Aristote : le statut des qualités premières, l’existence d’une intensité maximale de ces qualités, et la possibilité pour les corps simples d’exister à l’état pur. En croisant les commentaires au De caelo, au De generatione et corruptione et aux Meteorologica, son apport majeur consiste à faire apparaître, dans un corpus souvent lu à travers le seul prisme péripatéticien, l’influence structurante de Galien. En articulant les schèmes hylémorphiques d’Alexandre d’Aphrodise avec la théorie galénique des puissances naturelles, Averroès élabore une théorie du sensible inédite, critique à l’égard d’Avicenne, selon laquelle le cosmos est un système dynamique clos, dans lequel le mélange perpétuel, orchestré par le mouvement céleste, donne lieu à ce que l’on peut appeler une complexion cosmique : non pas un équilibre absolu, mais une somme réglée de complexions relatives, à la mesure de la diversité du sensible.
Psychotherapy chatbots have attained remarkable fluency, skill and ubiquity – having become the single most frequent reason people use artificial intelligence. Their uncanny ability to engage and validate is a two-edged sword – useful for the majority of users who are experiencing problems of everyday life or have milder mental disorders, but dangerous for the minority who have more severe problems (e.g. psychosis, bipolar disorder, self-mutilation, suicide, antisocial impulses, eating disorders, conspiracy theories, religious and political extremism). Chatbots are created to make money, without meaningful quality control, safety guardrails and external regulation. They will likely be misused to create addiction, reduce human contact, invade privacy, allow exploitation and create opportunities for marketing and political propaganda. Chatbots also make mistakes (’hallucinations’), deceptively cover them up and sometimes go rogue (acting outside the parameters set by their human programmers). Psychotherapy practitioners and associations are curiously complacent about the rapid emergence of artificial intelligence competition. Their passivity reflects ignorance about the power of chatbots, denial of their likely impact and arrogance regarding their capacities (e.g. ‘no machine will ever replace me’). This is both incorrect and foolhardy – human therapists expect to win in competition for most healthier patients and must train or retrain to do things artificial intelligence does poorly – working with the more seriously ill and in settings and situations that are more idiosyncratic, chaotic or quickly changing. If we can’t work with artificial intelligence, we are likely to be replaced by it. I will describe: (a) benefits of chatbot therapy, (b) its terrifying dangers, (c) its likely impact on human therapy and training and 4) ways we can adapt to the artificial intelligence threat.
Let $\Sigma$ be an alphabet and $\mu$ be a distribution on $\Sigma ^k$ for some $k \geqslant 2$. Let $\alpha \gt 0$ be the minimum probability of a tuple in the support of $\mu$ (denoted $\mathsf{supp}(\mu )$). We treat the parameters $\Sigma , k, \mu , \alpha$ as fixed and constant. We say that the distribution $\mu$ has a linear embedding if there exist an Abelian group $G$ (with the identity element $0_G$) and mappings $\sigma _i : \Sigma \rightarrow G$, $1 \leqslant i \leqslant k$, such that at least one of the mappings is non-constant and for every $(a_1, a_2, \ldots , a_k)\in \mathsf{supp}(\mu )$, $\sum _{i=1}^k \sigma _i(a_i) = 0_G$. In [Bhangale-Khot-Minzer, STOC 2022], the authors asked the following analytical question. Let $f_i: \Sigma ^n\rightarrow [\!-1,1]$ be bounded functions, such that at least one of the functions $f_i$ essentially has degree at least $d$, meaning that the Fourier mass of $f_i$ on terms of degree less than $d$ is at most $\delta$. If $\mu$ has no linear embedding (over any Abelian group), then is it necessarily the case that
where the right hand side $\to 0$ as the degree $d \to \infty$ and $\delta \to 0$?
In this paper, we answer this analytical question fully and in the affirmative for $k=3$. We also show the following two applications of the result.
1. The first application is related to hardness of approximation. Using the reduction from [5], we show that for every $3$-ary predicate $P:\Sigma ^3 \to \{0,1\}$ such that $P$ has no linear embedding, an SDP (semi-definite programming) integrality gap instance of a $P$-Constraint Satisfaction Problem (CSP) instance with gap $(1,s)$ can be translated into a dictatorship test with completeness $1$ and soundness $s+o(1)$, under certain additional conditions on the instance.
2. The second application is related to additive combinatorics. We show that if the distribution $\mu$ on $\Sigma ^3$ has no linear embedding, marginals of $\mu$ are uniform on $\Sigma$, and $(a,a,a)\in \texttt{supp}(\mu )$ for every $a\in \Sigma$, then every large enough subset of $\Sigma ^n$ contains a triple $({\textbf {x}}_1, {\textbf {x}}_2,{\textbf {x}}_3)$ from $\mu ^{\otimes n}$ (and in fact a significant density of such triples).
This article examines historical perceptions of the territorial extent of Bod, the Tibetan toponym for ‘Tibet’. In a bid to establish what area second-millennium authors (and audiences) may have pictured when this toponym was invoked, we analyse instructive passages from five historiographical works, mostly dating from between the twelfth and seventeenth centuries. The rough-hewn maps of Bod ‘Tibet’ that emerge from this procedure differ quite radically from one work to the next, and at times even between different passages from a single source. While one work may see ‘Tibet’ as the territory directly centered on the Tibetan Plateau’s south-central river valleys, another source may forward an image of a ‘Tibet’ that is thrice as large. Works may also allow for shifts in its borders from one political period to the next, or incorporate multiple incongruous territorial descriptions. This material helps answer what ‘Tibet’ meant in different periods and places, and to different people—questions that have only poorly been studied outside of modern political history. One relevant finding, among others, is that the notion of a ‘Tibet’ that covers a large part of the Tibetan Plateau, incorporating for instance sites in contemporary eastern Qinghai, was not in fact a modern innovation.
This article explores the systems of policing that emerged in the early Cape Colony (1652–1830). Contrary to previous historical scholarship that understood the institution to be largely nonexistent or of marginal importance to the colony’s political economic development, this article argues that the Cape colony’s systems of policing, which doubled as ad hoc military organizations, were not so much weak as privatized. It shows how this persistent tendency was motivated by the Dutch East India Company’s desire to maximize profits—though it manifested differently in different parts of the colony. Moreover, this article demonstrates that the mercantile economy that the company installed at the Cape ensured that private policing would become a vehicle of indigenous dispossession. In doing so, it seeks to contribute to the field of African carceral studies and understandings of processes of racialization in the early Cape.
This article is the introduction to the Special Issue on The Constitution of Political Economy. It provides an overview of six articles which in distinctive yet overlapping ways explore three key issues. First, how the economy and the polity are embedded in society. Second, how interdependence shapes institutional arrangements. Third, how different levels of aggregation determine levels of policy-making, notably the importance of intermediate institutions.
We derive the scale-by-scale uncertainty energy budget equation and demonstrate theoretically and computationally the presence of a self-similar equilibrium cascade of decorrelation in an inertial range of scales during the time range of power-law growth of uncertainty in statistically stationary homogeneous turbulence. This cascade is predominantly inverse and driven by compressions of the reference field’s relative deformation tensor and their alignments with the uncertainty velocity field. Three other subdominant cascade mechanisms are also present, two of which are forward and also dominated by compressions and one of which, the weakest and the only nonlinear one of the four, is inverse. The uncertainty production and dissipation scalings which may follow from the self-similar equilibrium cascade of decorrelation lead to power-law growths of the uncertainty integral scale and the average uncertainty energy which are also investigated. Compressions are key not only to chaoticity, as previously shown, but also to stochasticity.
Cardiac rhabdomyomas are the most common benign paediatric cardiac tumours. Arrhythmias and cardiac conduction abnormalities have both been described with these tumours and resolved with reduction in size of the tumours. Here, we present a case of a child who was prenatally diagnosed with multiple cardiac rhabdomyomas and cardiac arrhythmias and found to have ventricular pre-excitation after birth, in whom the tumours regressed, and pre-excitation resolved with 12 weeks of sirolimus and propranolol therapy. However, 8 weeks after cessation of sirolimus and propranolol therapy, tumour size increased, and manifest ventricular pre-excitation recurred and progressed to ventricular tachycardia. Subsequent follow-up after restarting sirolimus and propranolol therapy showed a significant reduction in tumour burden and resolution of pre-excitation.
Conclusions:
This finding underscores the need for risk stratification among patients with cardiac rhabdomyomas to identify those that need more prolonged medical treatment or closer monitoring.
A new species of Blastulospongia Pickett and Jell, 1983 from the middle Cambrian Devoncourt Limestone, Georgina Basin, Australia exhibits distinct perforation patterns characteristic of sphinctozoans. Recognition as a sphinctozoan-grade sponge confirms the poriferan affinity of this enigmatic genus, which appeared prior to the development of other hypercalcified sponge forms of chaetetids and stromatoporoids. Blastulospongia bouliaensis new species occurs together with four species of primitive spicular radiolarians: Echidnina irregularis Won in Won and Iams, 2002, Parechidnina aspinosa Won in Won and Below, 1999, Palaeospiculum reedae Won in Won and Below, 1999, and Palaeospiculum devoncourtensis Won in Won and Below, 1999. Micro-computed tomographic (MCT) analysis of Parechidnina aspinosa reveals its skeletal construction through the fusion of unirayed spicules, indicating a close phylogenetic link with archeoentactinids. Blastulospongia bouliaensis n. sp. and Palaeospiculum devoncourtensis represent promising Miaolingian accessory species for biostratigraphy during the Drumian-Guzhangian interval.
A large empirical literature examines how judges’ traits affect how cases get resolved. This literature has led many to conclude that judges matter for case outcomes. But how much do they matter? Existing empirical findings understate the true extent of judicial influence over case outcomes since standard estimation techniques hide some disagreement among judges. We devise a machine learning method to reveal additional sources of disagreement. Applying this method to the Ninth Circuit, we estimate that at least 38% of cases could be decided differently based solely on the panel they were assigned to.
To what extent can intellectual humility be formalized? One natural idea links humility to open-mindedness, captured by a regularity principle: no coherent hypothesis should get probability zero. While debates over regularity often concern infinities, my objection is different. Regularity is feasible only for ideally rational, logically omniscient agents. Yet on a common view, humility involves appreciating our limitations—including our failure to be such agents. So whatever its merits for ideal cognition, regularity is a poor model for human humility. Indeed, taking it as such would itself be un-humble, by failing to appreciate our own epistemic limitations.
The decision to work is an important yet understudied facet of women’s economic empowerment. This study explores the relationship between married women’s agency over the decision to work, workforce participation, and control over financial resources, using cross-sectional survey data collected in 2022 in India’s three most populous states: Bihar, Uttar Pradesh, and Maharashtra. Employing logistic regression, inverse probability weighting, and partial identification approaches, we demonstrate that married women in all three states are significantly more likely to engage in paid work when they alone have the final say over the decision to work, compared to when their spouse is the primary decision-maker. We also find that sole decision-making about paid work is positively related to married women’s control over money in Bihar and Maharashtra, and with savings and remittances in Maharashtra. In Maharashtra, women who jointly decide about employment with their spouse are also more likely to work than women whose husbands are the sole decision-makers. Joint decision-making is positively associated with women’s control over money in all three states. Our study highlights work-related agency as an important pathway to married women’s economic opportunities and inclusion in India, and is among the first to empirically examine the relationship between women’s work-related decision-making and economic outcomes. These results align with existing evidence on the positive relationship between women’s household bargaining power and health and human capital outcomes, and offer support for designing programmes to promote women’s participation in the workforce.
The Llandoverian (Telychian) Schoolcraft Formation of Schoolcraft County in the Upper Peninsula of Michigan includes several intervals of exceptional preservation marked by abundant specimens of the noncalcified macroalga Thalassocystis striata Taggart and Parker, 1976. Here, two new noncalcified macroalgal species are described from one of these algal-Lagerstätten intervals. The monopodial thallus of Archaeobatophora gulliverensis new species resembles that of the living dasycladalean green alga Batophora Agardh, 1854 and consists of a cylindrical main axis bearing whorls of branched laterals. It is the second species to be assigned to Archaeobatophora Nitecki, 1976, the type species of which is known only from the Upper Ordovician of neighboring Delta County and the diagnosis of which is emended herein. The thallus of Earltonella swinehartii new species consists of a horizontal stolon that bears a series of upright pinnate fronds. This taxon broadly resembles the living bryopsidalean green alga Caulerpa Lamouroux, 1809 and is the second species to be assigned to Earltonella LoDuca in LoDuca et al., 2023, a genus otherwise known only from approximately age-equivalent strata in the Lake Timiskaming area of Ontario. Additionally, a new Thalassocystis striata occurrence is reported from the Schoolcraft Formation in neighboring Mackinac County, extending eastward the geographic range of this Codium-like bryopsidalean taxon within the Michigan Basin. Viewed in broader terms, the two new species show complex thallus morphologies consistent with a previously documented large-scale morphological pattern in the early Paleozoic evolutionary history of macroalgae and contribute to an emerging understanding of major early Paleozoic radiations of both dasycladalean and bryopsidalean algae that produced, by the mid-Silurian, diverse floras of siphonous green macroalgae broadly similar to those that thrive today in Florida Bay and the Bahama Banks.
Critical CHD refers to life-threatening cardiac anomalies present at birth that require surgical or catheter-based intervention within the first year of life. Without punctual diagnosis and treatment, these conditions can result in significant morbidity or mortality. In high-income countries like the United States (U.S.), early detection and management of Critical CHD have been greatly improved through universal prenatal screening, pulse oximetry screening, regionalised care, and subspecialty training. In contrast, Vietnam, a low- and middle-income country, faces persistent challenges. The absence of newborn screening policies and limited prenatal detection infrastructure leads to delayed diagnoses. Paediatric cardiac expertise and surgical services are largely confined to urban centres, leaving rural areas underserved. Vietnam also lacks national CHD registries, standardised referral pathways, and consistent training programmes, impeding quality improvement and equitable access. This manuscript compares the U.S. and Vietnamese Critical CHD systems, highlighting structural, infrastructural, and workforce-related disparities. We identify barriers, key areas for intervention, and offer targeted strategic considerations to address these discrepancies. We strongly believe that efforts to implement universal newborn screening, develop regional cardiac hubs with mandatory outreach support to rural proximity, expand workforce training, invest in ICU infrastructure, and establish national data systems are of immediate need. These reforms could significantly improve survival and outcomes for children with Critical CHD in Vietnam and inform similar efforts in other low- and middle-income countries.
Policy making in areas of scientific uncertainty may be shaped by the public’s stated preferences (SP). SP surveys provide respondents with information about the scenario, typically from expert sources. Here, we tested whether respondents’ pre-existing confidence in the ability of experts in general to provide reliable information was associated with (a) status quo bias, (b) response certainty and (c) willingness to pay (WTP) estimates. Using 670 responses to a 2020 choice experiment on microplastic restrictions in the UK, we show that being ex ante more confident was significantly related to less frequent status quo choices and higher response certainty. However, we only observed differences in mean WTP for our ‘microplastics released’ attribute. Our findings suggest that confidence in expert-provided information shapes how respondents engage with SP surveys, particularly in contexts of scientific uncertainty. Future work to further understand determinants and consequences of perceived expert trustworthiness would be insightful.
Why was New Jersey able to construct a more robust air pollution control regime after World War II while Ohio lagged far behind? Moreover, why did Ohio — a pioneer in early air pollution control efforts — fall behind New Jersey during this period? Both of these states were heavily-industrialized, densely populated, and concerned about maintaining a competitive economy. This paper explores the role played by institutional legacies in shaping bureaucratic politics as well as the development of effective government agencies. It demonstrates that statewide action on air pollution was primarily shaped by the states’ institutional legacies (or lack thereof) from the Progressive Era. In Ohio, extant urban pollution agencies remained the center of pollution control during the 1960s even as policymakers recognized their limited capacity to address air pollution. In contrast, policymakers in New Jersey could design a statewide agency virtually from scratch without disrupting existing institutions and their relationships with affected industries. While it took some time for New Jersey to develop an effective state agency, policymakers and pollution control advocates could focus on improving one statewide agency rather than several urban agencies, thus easing their path to developing an agency capable of regulating corporate activity.