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Understanding the mechanisms of major depressive disorder (MDD) improvement is a key challenge to determining effective personalized treatments.
Methods
To identify a data-driven pattern of clinical improvement in MDD and to quantify neural-to-symptom relationships according to antidepressant treatment, we performed a secondary analysis of the publicly available dataset EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care). In EMBARC, participants with MDD were treated either by sertraline or placebo for 8 weeks (Stage 1), and then switched to bupropion according to clinical response (Stage 2). We computed a univariate measure of clinical improvement through a principal component (PC) analysis on the variations of individual items of four clinical scales measuring depression, anxiety, suicidal ideas, and manic-like symptoms. We then investigated how initial clinical and neural factors predicted this measure during Stage 1 by running a linear model for each brain parcel’s resting-state global brain connectivity (GBC) with individual improvement scores during Stage 1.
Results
The first PC (PC1) was similar across treatment groups at stages 1 and 2, suggesting a shared pattern of symptom improvement. PC1 patients’ scores significantly differed according to treatment, whereas no difference in response was evidenced between groups with the Clinical Global Impressions Scale. Baseline GBC correlated with Stage 1 PC1 scores in the sertraline but not in the placebo group.
Using data-driven reduction of symptom scales, we identified a common profile of symptom improvement with distinct intensity between sertraline and placebo.
Conclusions
Mapping from data-driven symptom improvement onto neural circuits revealed treatment-responsive neural profiles that may aid in optimal patient selection for future trials.
The rise of antagonism between the German and Czech nationalist activists in the mid-19th century has been neither clearly explained nor convincingly dated. Although this is a topic closely linked to the history of nationalism, the state of research has paradoxically been misguided by the nationalist approach adopted by historians analyzing it. The reason is that nationalism was not the cause but just one response to a greater phenomenon. The aim of the article is therefore to clarify the German-Czech relationship in the broader context of European history and the history of international relations using the perspective of geopolitics and security. As it claims, it was not cultural, linguistic, or constitutional issues but the fear of external threats that caused the mutual distrust of political activists that led to hostility and conflicting policies. Under the impact of international events and within the context of their relations to other international actors this process originated in 1839 by the latest. During subsequent years it developed rapidly and became obvious during the 1848 revolutions. The article thus reveals that this year did not represent the beginning but merely another chapter in a process that had begun nearly a decade earlier.
Measurements of the radiocarbon (14C) content of subannual wood cellulose samples over the 1963 bomb spike have revealed an apparent delay between the increase in atmospheric radiocarbon content and that of wood cellulose. This delay is apparent in both coniferous and deciduous tree species and is of a magnitude of approximately 4 weeks. The delay in wood cellulose 14C change as measured in a Sitka spruce from Washington state, USA, was previously used to estimate the relative influence of tree physiological effects contra environmental effects. We repeated the measurements with the increased measurement precision of today’s AMS systems and compare the new results to the ones of a Scots pine tree from Trondheim, central Norway and a white oak from Oregon state, USA. The results challenge the assumption that the 14C tree ring records directly show the atmospheric 14C concentration of a homogeneous, zonally well-mixed atmosphere. Instead, the apparent 1963 delay reflects local influences of the ecosystem and tree physiology. The 1963/1964 data allows for exploratory modeling of the effects of biospheric decay CO2 and local environmental influences assuming the absence of stored photosynthates from the previous year. Compared to the 10–30% contribution from biospheric CO2, the effects of delayed incorporation of carbon into the wood cellulose and the effect of stored photosynthate are small in the conifers. Highly detailed 14C records of stem cellulose can, in combination with stable isotope studies, contribute to our understanding of variability of the local carbon cycle, climate, and the environment.
Insight into plasma dynamics under usual pulsed laser deposition (PLD) conditions for NiO thin film growth is provided by implementing angle- and time-resolved Langmuir probe (LP) methods. The selective separation generated an acceleration region that separates ions based on nature and ionisation state. A maximum of the kinetic energy for most plasma components was found for 0.5–2 Pa Ar, while the time-resolved analysis revealed a multipeak evolution of the electron temperature, which widened and shifted with increasing pressure. Evidence of two temperature structures for NiO plasma is presented, and the estimation of the accelerating field generated between the two plasma structures reveals selective in acceleration in the first microsecond. The acceleration field has a maximum value for the O2 atmosphere at approximately 2 Pa, which shows the separation between drift-dominated kinetics and reaction-based dynamics. Further investigation in this 2 Pa region revealed the appearance of a perturbation consistent with the formation of a plasma fireball on the probe. The dynamics of these perturbations is affected by the nature of the gas having different incubation times.
This study investigates the strong influence of a splitter plate on two- and three-dimensional wake transitions of a circular cylinder. Direct numerical simulations and Floquet analyses are conducted over a parameter space including Reynolds numbers (Re) of 10–480 and non-dimensional plate lengths (L/D) of 0–6. With the increase in L/D, the critical Re for the onset of vortex shedding (Recr2D) increases monotonically. The delayed onset of vortex shedding with elongation of the body is physically explained. The critical Re for the onset of three-dimensionality (Recr3D) and the three-dimensional wake instability modes and structures are also significantly altered by the splitter plate. Compared with an isolated cylinder, the Recr3D for L/D = 1 is significantly reduced via a long wavelength mode, whereas the Recr3D for L/D = 2–6 is significantly increased via other modes. For each L/D, with increasing Re over the wake transition process, the spanwise wavelength of the wake structure gradually decreases, and the wake structure becomes increasingly chaotic. The strong influence of the splitter plate on the formation of the primary vortices and three-dimensional wake structures alter the hydrodynamic characteristics strongly. In particular, optimal lift reduction is achieved at L/D ∼ 1. In addition, the existence/absence of a hysteresis effect at the onset of three-dimensionality is identified by three methods. Among which, the method involving the Landau equation may be contaminated by initial transients induced by stable Floquet modes and may thus lead to a false conclusion on the existence/absence of hysteresis.
This article explores the mechanics of institution building through a case study of Peru’s tax authority reform in the early 1990s. An agency riddled with corruption and despondency became a model bureaucracy oriented toward public service under the leadership of a career civil servant with a religious background. The explanation combines systemic factors associated with institutional change with other, less well-known forces. The profound socioeconomic crisis that had struck Peru at the time opened a window for reform. More significantly, the analysis focuses on the struggle to supplant old and enforce new institutional values. Management policy played a role by fostering a predisposed workforce. However, it was the charismatic performance of the reform leader and his task force, articulated around a nation-saving narrative, that instilled the belief that change was possible, encouraged employees to embrace new values, and paradoxically enabled the creation of an agency with a Weberian ethos. Subsequent developments hint at the limits of charismatic state building.
Commentary on the election of Pope Leo XIV has been framed in terms drawn from political and cultural oppositions: conservative vs liberal, traditionalist vs progressive, made vivid by the 2024 film Conclave based on Robert Harris’s 2016 novel. Part of my concern is to urge rejection of these as general terms of analysis of Catholicism, or at least to circumscribe their applications to matters inessential to Catholic faith and morals per se. In aid of that, and by way of broader purpose, I discuss the nature of Catholicism itself. Observing the long history of challenges, crises, and divisions, I then proceed to distinguish between subjective and objective modes of identifying the nature of individuals and institutions. Catholicism has a robust objective nature comprising a synthesis of Hebrew and Christian scripture, apostolic tradition, conciliar and other authoritative teachings, and sacramental practices, together consolidated and expressed in orthodoxy and orthopraxy. Political and cultural classifications are irrelevant to and distracting from this identification.
Expanding crop diversity is essential to address the imminent challenges of agriculture. This is especially true for organic farming, which relies on locally adapted species and varieties. Recently, participatory research approaches have emerged as effective means to support this endeavour. In this study, we collaborated with several stakeholders in the Lyon region, France, to evaluate three minor species related to common wheat (Triticum aestivum subsp. aestivum): einkorn (Triticum monococcum subsp. monococcum), emmer (Triticum turgidum subsp. dicoccum) and spelt (Triticum aestivum subsp. spelta (L.) Thell). First, we assessed the agronomic characteristics of each species, highlighting a distinction of einkorn that was associated with high tillering, high protein content, a long phenological cycle, small kernels and low relative yields. Second, we compared intra-species variabilities, revealing greater variation in emmer and spelt. Lastly, outcomes of the participatory approach, including testing adaptive methods and fostering collective learning, may interest other participatory research groups.
We construct a measure (fLMA) of the extent to which neighboring firms hire similar types of workers, based on the similarity between the labor profile of a firm and that of its locality. We show that a firm’s innovation is positively related to fLMA. The enhanced labor mobility induced by higher fLMA is an important channel for this positive relation. This relation is stronger when firms have increased outside job opportunities for employees, increased knowledge spillovers via coworkership, and more employee stock options. Innovation is higher when intellectual property ownership is with employers, not employees. This effect increases in fLMA.
This paper investigates the permanent effect on total factor productivity (TFP) of temporary shocks. We estimate a structural vector autoregression to test the predictions of endogenous growth models over the business cycle. According to theory, the stock of technological knowledge promotes its flow as researchers “stand on the shoulders of giants.” Therefore, if R&D investment is pro-cyclical—as data show and theory predicts—a recession leads to a temporary deviation of the R&D level from its trend, thus reducing new knowledge creation. The lost technological advancements cause the economy to follow a parallel but permanently lower growth path. Our findings align with the primary theoretical prediction. Quantitatively, the US economy forgoes approximately 1.3% in TFP following an increase in cyclical unemployment that peaks at 1 percentage point above the mean. The historical variance decomposition shows a strong positive effect during the boom of the late 1960s and strong negative effects around the Volcker disinflation period and the Great Recession. Finally, we estimate the effects on R&D of a TFP shock to differentiate between different explanations on how the R&D pro-cyclicality arises. Our results align with models where financial frictions or nominal rigidities drive it.
Drone technology and digital image analysis have enabled significant advances in precision agriculture, especially in site-specific treatment of weed escapes in crop fields. This study evaluated a pipeline for weed detection in multispectral drone imagery, along with site-specific herbicide application, using a remotely piloted aerial application system (RPAAS) targeting late-season weed escapes in rice with a selective postemergence rice herbicide, florpyrauxifen-benzyl. The efficacy of the RPAAS-based herbicide application with geocoordinates of weed escapes obtained manually or based on image analysis was compared with conventional backpack broadcast spray. The weed species targeted were barnyardgrass, Amazon sprangletop, yellow nutsedge, and hemp sesbania. A Python-based rice–weed detection model was developed using the canopy height model and spectral reflectance of weeds and rice plants. Results indicate that the accuracy of image-based detection for late-season weed escapes in rice was highest for hemp sesbania (95%), followed by Amazon sprangletop (87%) and yellow nutsedge (74%), with barnyardgrass showing the lowest accuracy at 62%. The study found that the backpack broadcast method had the highest efficacy in weed control, followed by the RPAAS method using manually obtained geocoordinates and those based on image analysis. Site-specific herbicide application using RPAAS resulted in a 45% reduction in herbicide compared to the broadcast backpack application. Moreover, the RPAAS site-specific application method for late-season treatment minimized the field area affected by herbicide injury and protected rice grain yields compared to the broadcast method. Overall, the utility of unmanned aerial sprayer–based detection and site-specific treatment of late-season weed escapes in rice has been demonstrated in this research, but further improvements in weed detection efficacy and the accuracy of targeting plants with RPAAS are necessary.
In the early 1970s, Christopher Stone and Peter Singer influentially rejected the anthropocentrism of liberalism, contending that animals and nature deserved moral and legal consideration independent of humans. This article historicizes the emergence of nonhuman personhood by showing how they and other writers attempted to dismantle liberalism’s anthropocentrism at a dynamic time in humanist politics. Writers asserted nonhuman personhood as a continuation of 1960s liberation movements, employing the narrative of a “natural” extension of rights and equality from marginalized humans to nonhumans. This determinism, however, obscured nonhumans’ specific inability to make political claims. Drawing on the incipient 1970s human rights movement, writers circumvented this problem of political agency by emphasizing nonhumans’ capacity to suffer. Suffering allowed humans to see themselves in nonhumans and thus recognize their personhood. This turn to empathetic identification as the driver of historical change inaugurated an anti-anthropocentric humanism that extended personhood beyond humanity but reinscribed a more fundamental distinction between those able and those unable to make political claims. Drawing on both 1960s challenges to humanism and 1970s humanist preoccupation with suffering, anti-anthropocentric humanism preserved the very limitations of liberal politics into a new definition of personhood that effaced political agency from both personhood and history.
Kongish Daily, a Facebook page promoting Kongish – a creative, critical, and colloquial form of Hong Kong English with Cantonese inflections – has attracted a following in social media over the past decade. It has also sparked interest among sociolinguists interested in (post-)multilingual developments in East Asia. This study is built on Hansen Edwards’s (2016) premise that Hong Kong English would gain wider acceptance in Hong Kong as the cultural identity of local language users shifted amidst sociocultural transformations. We first provide an overview of the Kongish phenomenon, followed by a qualitative study involving 30 active Kongish users from diverse age groups, genders and occupations. Through semi-structured interviews, we explore users’ perceptions of language and identity. Our findings support Hansen Edwards’s prediction regarding the strengthening of Hong Kongers’ cultural identification, while revealing an evolving, counter-stereotypical Hong Kong culture as well as an opinion divide on the future trajectory of Kongish.
Patients with schizophrenia have a significantly elevated risk of mortality. Clozapine is effective for treatment-resistant schizophrenia, but its use is limited by side-effects. Understanding its association with mortality risk is crucial.
Aims
To investigate the associations of clozapine with all-cause and cause-specific mortality risk in schizophrenia patients.
Method
In this 18-year population-based cohort study, we retrieved electronic health records of schizophrenia patients from all public hospitals in Hong Kong. Clozapine users (ClozUs) comprised schizophrenia patients who initiated clozapine treatment between 2003 and 2012, with the index date set at clozapine initiation. Comparators were non-clozapine antipsychotic users (Non-ClozUs) with the same diagnosis who had never received a clozapine prescription. They were 1:2 propensity score matched with demographic characteristics and physical and psychiatric comorbidities. ClozUs were further defined according to continuation of clozapine use and co-prescription of other antipsychotics (polypharmacy). Accelerated failure time (AFT) models were used to estimate the risk of all-cause and cause-specific mortality (i.e. suicide, cardiovascular disease, infection and cancer).
Results
This study included 9,456 individuals (mean (s.d.) age at the index date: 39.13 (12.92) years; 50.73% females; median (interquartile range) follow-up time: 12.37 (9.78–15.22) years), with 2020 continuous ClozUs, 1132 discontinuous ClozUs, 4326 continuous non-ClozUs and 1978 discontinuous Non-ClozUs. Results from adjusted AFT models showed that continuous ClozUs had a lower risk of suicide mortality (acceleration factor 3.01; 99% CI: 1.41–6.44) compared with continuous Non-ClozUs. Continuous ClozUs with co-prescription of other antipsychotics exhibited lower risks of suicide mortality (acceleration factor 3.67; 1.41–9.60) and all-cause mortality (acceleration factor 1.42; 1.07–1.88) compared with continuous Non-ClozUs. No associations were found between clozapine and other cause-specific mortalities.
Conclusions
These results add to the existing evidence on the effectiveness of clozapine, particularly its anti-suicide effects, and emphasise the need for continuous clozapine use for suitable patients and the possible benefit of clozapine polypharmacy.
Harm reduction is one of the most controversial and widely discussed approaches in public health and social policy, addressing a broad range of pressing societal issues, including drug addiction, sex work, alcohol and tobacco use, and homelessness. Surprisingly, however, harm reduction has received very little philosophical scrutiny. In this article, I aim to fill this gap. First, I provide a systematic analysis of the core features and normative commitments of harm reduction. Second, I propose a novel, relational egalitarian justification for harm reduction. I argue that the provision of harm reduction services is not solely or primarily a matter of mitigating the negative consequences associated with high-risk behaviours. Rather, most fundamentally, it is the appropriate response to the status of vulnerable individuals as equal members of society.
Artificial intelligence (AI) is transforming nearly every domain of science, and scholarly publishing is no exception. From automated language editing to machine-assisted peer review and large-scale content analysis, AI tools are increasingly embedded in scientific writing and publishing. The response from the scientific community has ranged from cautious optimism to outright skepticism. This viewpoint aims to articulate an editorial perspective on the integration of AI into scientific writing and publishing, evaluating both the opportunities and tensions that arise, and offering principles for navigating the road ahead.
Words in Tagalog/Filipino can be either penult-prominent or ultima-prominent. Scholars have been divided on whether the language has stress, or only phonemic vowel length in penults and default phrase-final prominence. Using a corpus of Original Pilipino Music, we find that both prominent penults and prominent ultimas are set to longer notes and stronger beats, even in phrase-medial position. We further find that among pre-tonic syllables, those that would plausibly attract secondary stress are mostly set to longer notes and stronger beats. Text-setting does not faithfully reflect differences in phonetic cues between the two types of prominence, nor is it sensitive to presumed phonetic differences between high and low vowels. We conclude that songwriters’ text-setting decisions reflect phonological stress in Filipino, and that both penult-prominent and ultima-prominent words bear stress.
How can wellbeing for all be improved while reducing risks of destabilising the biosphere? This ambition underlies the 2030 Agenda but analysing whether it is possible in the long-term requires linking global socioeconomic developments with life-supporting Earth systems and incorporating feedbacks between them. The Earth4All initiative explores integrated developments of human wellbeing and environmental pressures up to 2100 based on expert elicitation and an integrated global systems model. The relatively simple Earth4All model focuses on quantifying and capturing some high-level feedback between socioeconomic and environmental domains. It analyses economic transformations to increase wellbeing worldwide and increase social cohesion to create conditions that are more likely to reduce pressures on planetary boundaries. The model includes two key novelties: a social tension index and a wellbeing index, to track societal progress this century. The scenarios suggest that today's dominant economic policies are likely to lead to rising social tensions, worsening environmental pressures, and declining wellbeing. In the coming decades, unchecked rising social tensions, we hypothesise, will make it more difficult to build a large consensus around long-term industrial policy and behavioural changes needed to respect planetary boundaries. We propose five extraordinary turnarounds around poverty, inequality, empowerment, energy and food that in the model world can shift the economy off the current trajectory, improve human wellbeing at a global scale, reduce social tensions and ease environmental pressures. The model, the five (exogenous) turnarounds and the resulting two scenarios can be used as science-policy boundary objects in discussions on future trajectories.
Non-technical summary
Our world is facing a convergence of environmental, health, security, and social crises. These issues demand urgent, systemic solutions now that address not only environmental but also social dimensions. Weak political responses have stalled progress on the Sustainable Development Goals and the Paris Agreement. We have developed scenarios that explore interconnections between possible climate futures, rising living costs, and increasing inequalities that fuel populism and undermine democracy to the year 2100. We propose five turnaround solutions – energy, food and land systems, inequality, poverty, and gender equality – that if enacted are likely to provide wellbeing for a majority of people plus greater social cohesion. This will support long-term industrial policies and behavioural change to reduce emissions and protect the biosphere toward a long-term goal of living on a relatively stable planet.
Social Media summary
Our dominant economic model is destabilising societies and the planet. Earth4All found 5 turnarounds for real system change.
Grice’s foundational conversation model has inspired a range of influential developments, with various approaches to merging the maxims. This paper addresses unresolved controversies and circular dependencies that have fuelled assumptions of interdependence among the principles. It provides a revision of both Grice’s cooperative principle and the principles of truthfulness, relevance, informativeness and clarity, and extends them to include a principle of social conformity, which I collectively refer to as the TRICS-Principles. I demonstrate that the TRICS-Principles operate independently of each other at different levels and show the extent to which the other principles may function under the umbrella of a flouted principle of truthfulness. Furthermore, I distinguish the principle of social conformity from the concept of politeness, offering a nuanced perspective on their relationship. Finally, I provide new insights into factors influencing shifts in the prioritisation of the TRICS-Principles.