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Aneuploidy in oocytes is a leading cause of implantation failure, miscarriage and congenital disorders. During meiosis, proper timing of chromosome segregation is regulated by the spindle assembly checkpoint (SAC) and the anaphase-promoting complex/cyclosome (APC/C). However, how pharmacological manipulation of these regulatory pathways affects aneuploidy remains incompletely understood. In this study, we investigated whether SAC inhibition by reversine induces aneuploidy in mouse oocytes and whether partial inhibition of APC/C by proTAME can alleviate these errors. Germinal vesicle (GV) oocytes were matured in vitro in the presence of various concentrations of reversine. To optimize the timing of treatment, oocytes were exposed to reversine for 0, 3, 5 or 7 h, followed by culture with or without proTAME. A proTAME-only group (2.5 nM) was also included. Chromosome spreads were analyzed at the metaphase II (MII) stage to determine aneuploidy rates. Reversine (5 nM) yielded an MII maturation rate of 80.5% but induced a high aneuploidy rate of 77.0%. Sequential treatment with 2.5 nM proTAME significantly reduced aneuploidy to 33.3%. In contrast, proTAME alone led to 79.0% aneuploidy, suggesting its effect is contingent upon prior SAC disruption. These results indicate that reversine compromises chromosomal integrity, while appropriately timed, low-dose proTAME can partially rescue segregation errors. Our findings underscore the potential of pharmacologically regulating APC/C activity to reduce aneuploidy and enhance oocyte quality, offering new avenues for improving outcomes in assisted reproductive technologies.
‘English at the grassroots’ refers to English used by non‑elite speakers from lower social strata, with diverse acquisition paths, proficiency levels and usage. These Englishes are often heterogeneous, shaped by informal contexts and professions. English linguistics has long examined English as a pluricentric language, focusing on its use across first language (L1), second language (L2) and foreign language (FL) contexts, often through corpora, which predominantly represent upper‑middle‑class speakers. However, English is used in socially stratified societies, and sociolinguistic research has explored how language use correlates with lower social classes, especially in L1 varieties and multilingual contexts. Despite the historical focus on elites in L2/FL English acquisition and use – often due to colonial education systems – English has also spread to lower social strata globally. Yet, access to English is said to often correlate with socio‑economic status (SES), especially where education is not universally accessible. Nevertheless, SES does not necessarily always predict that one cannot use some form of English for communicative purposes. Non‑educational spaces – such as churches, homes, and social networks – play a crucial role in English acquisition and use outside formal education. These ‘grassroots’ efforts reflect resourcefulness in overcoming systemic barriers, enabling individuals to use English as linguistic capital for mobility, communication, and opportunity, especially in outer circle countries lacking a common indigenous lingua franca.
Autism Spectrum Disorder (ASD) is defined as a unidimensional condition, and autism traits are measured on a continuum where the high end of the spectrum represents individuals likely to have an ASD diagnosis. However, the large heterogeneity of ASD has thrown this unidimensional conceptualization into question. With the exact underlying cause(s) of autism yet to be identified, there is a pressing need to establish core, underlying dimensions of ASD that can capture heterogeneity within the autism spectrum, thereby better specifying both autistic traits and ASD symptoms. Here we describe one important transdiagnostic dimension, the cognitive rigidity-flexibility dimension, that may impact autistic traits and symptoms across symptom-relevant cognitive domains. We first discuss how diminished cognitive flexibility manifests in core autistic traits and autism symptoms in perception, attention, learning, social cognition, and communication. We then propose to supplement assessments of autistic traits in the general population and autism symptoms in individuals with an ASD diagnosis with a comprehensive batter of cognitive flexibility measures in these symptom-relevant domains. We conjecture that systematic differences in domain-general versus domain-specific cognitive flexibility can distill subgroups within the autism phenotype. While we focus on the cognitive flexibility dimension here, we believe that it is important to extend this framework to other higher order dimensions that can capture core autism symptoms and transdiagnostic symptom severity. This approach can characterize the latent, multi-faceted structure of autism, thereby yielding greater precision in diagnostic classification and the creation of more targeted interventions.
Alcohol use disorders (AUDs) often coexist with psychotic disorders. Both are common and each can cause or perpetuate the other. Comorbid diagnoses are multifactorial in origin, and both diagnostically and therapeutically challenging. This article is a narrative review of the epidemiology, diagnosis and management of comorbid AUDs and psychotic disorders. Although there is a lack of robust evidence on many aspects of this association, AUDs have been repeatedly shown to worsen outcomes in individuals with schizophrenia. The importance of a rigorous approach to diagnosis is emphasised. Three main treatment strategies emerge: considering particular antipsychotic drugs, relapse-prevention medication and engagement with a number of psychosocial interventions.
This article examines the connections between existing democratic deficits in law and contemporary democratic backsliding processes. To undermine the democratic process, present-day autocrats employ various legal strategies, including enacting new legal institutions (such as constitutional amendments or key statutory reforms) or manipulating existing ones. Focusing on a legal legacy of military rule in Turkey, the Specially Authorized Courts, this study argues that in consolidating power, autocrats also capitalize on pre-existing authoritarian zones within legal systems. In Turkey’s case, the AKP government has leveraged the exceptional procedures of Specially Authorized Courts to silence adversaries while simultaneously framing its reforms to the structure of these courts and the trials held at these courts as efforts to democratize the country and eradicate authoritarian legacies. As a result, the AKP masked its repressive actions behind a narrative of democratization in the early stages of Turkey’s democratic regression. Overall, the article presents both the coercive and legitimating uses of pre-existing “zones of authoritarianism” in law in contemporary processes of democratic backsliding. In doing this, it highlights how aspiring autocrats exploit the histories embedded in legal institutions to obscure their repressive actions.
Visual methods of surveying snakes are subject to observer bias and their accuracy is often questioned. Data collection by non-specialists offers an alternative way to record sightings. We present citizen science as a valuable tool for surveying the viperid snake Lachesis rhombeata, yielding more data than a traditional visual census in a remnant of the Atlantic Forest in north-east Brazil. From visits to local museum/university collections and a literature search, we obtained only 10 georeferenced historical records for this species in the study area dating from 1990 to 2020. In 218 h of visual field surveys during 2022 and 2023, covering 15,000 m2, we did not locate any L. rhombeata individuals, probably because their low population density and cryptic habits made their detection difficult. However, during the same period we acquired 110 georeferenced records through citizen science. The high number of records from citizen science underscores the value of this approach when working with an elusive and threatened snake. Lachesis rhombeata is often implicated in human–wildlife conflict but engaging local people in the project led to positive behavioural changes. Through citizen science we were able to examine live individuals, map the species’ current distribution, investigate threats to its survival and contribute data for studies on taxonomy, diet, home range, diseases and ethno-herpetology.
This article examines the tabular presentations in Sima Qian’s Shi ji and Gu Donggao’s Chunqiu dashi biao through the lens of a siege in 630 bce. Recognized as exemplary historical tables of the Spring and Autumn Period, the two tables process historical narratives at both micro and macro levels in an unprecedented manner, aiming to provide a larger picture of general historical trends. By emphasizing a visual and spatial representation of history in its tabular design, the Shi ji table invites the reader to examine the text nonlinearly and to construct a dialectical relationship between it and related narrative chapters. On the other hand, Gu’s text-oriented tables, usually misunderstood as a mere continuation of those in the Shi ji, require a linear reading and cannot directly produce a visual representation of the general patterns of the Spring and Autumn Period. However, to compensate for the lack of a visual overview, Gu composed “impromptu poems” (kouhao), which orally sketch general historical trends, to help beginners memorize the history of the Spring and Autumn Period. This article aims to demonstrate the use of tabulation at the crucial beginning point of Chinese historiography and its reinvention in the late imperial period.
For young people with eating disorders (EDs), family-based therapy (FBT) is generally recommended as first-line treatment. Although there is an abundance of evidence demonstrating the efficacy of FBT, less than half of young people achieve full remission with this treatment. Enhanced cognitive behaviour therapy (CBT-E) is an established alternative to FBT, demonstrating effectiveness in individuals who have not achieved full remission with FBT. It is also recommended when family therapy is unacceptable, contraindicated, or ineffective. Despite some overlap – particularly in addressing maintaining factors and prioritising weight normalisation – the two treatments diverge significantly in conceptualisation of the eating disorder, proposed mechanisms of action, role of both young people and parents, and strategies and processes of therapy. These differences may contribute to one treatment being effective where the other has not, but can present challenges and difficulties for the young person, family and clinician when transitioning from FBT to CBT-E. In this paper, we provide guidance for clinicians delivering CBT-E with young people who have a history of FBT treatment. We highlight common issues encountered among this cohort, discuss how they can present a barrier to successful implementation of CBT-E, and describe solutions.
Key learning aims
(1) To learn the commonly encountered barriers to treatment when implementing CBT-E for young people who have previously engaged in FBT.
(2) To learn strategies to overcome these barriers focusing on the young person, parents and multi-disciplinary team.
The fall of the Western Zhou Dynasty “left behind” the regional states of China’s central plain, creating a situation perhaps unique in history: the near-erasure of a colonizing power while its colonies continued to thrive. That the Western Zhou regime, despite its loose authority in the Guanzhong, can be considered a “colonizing” entity is here argued both in light of archaeological and textual evidence. Over time its destruction became re-imagined as a kind of traumatic inciting incident of the sort that many diasporic groups recall as the cause of their diasporic status. Just as with other diasporic groups, existing traditions and gaps in memory are filled in by re-imagined accounts and moral lessons displaying clear concern for the preservation of identity and discomfort with “outsiders.” This new reading of the Zhou period opens up a new angle by which Warring States texts—especially those including the Confucian canon—must be re-read, explaining such things as Confucian concerns about traditionalism as absolutely understandable given the wider diasporic discourse that emerged in the Eastern Zhou period.
Politicians appeal to social groups to court their electoral support. However, quantifying which groups politicians refer to, claim to represent, or address in their public communication presents researchers with challenges. We propose a supervised learning approach for extracting group mentions from political texts. We first collect human annotations to determine the passages of a text that refer to social groups. We then fine-tune a transformer language model for contextualized supervised classification at the word level. Applied to unlabeled texts, our approach enables researchers to automatically detect and extract word spans that contain group mentions. We illustrate our approach in two applications, generating new empirical insights into how British parties use social groups in their rhetoric. Our method allows for detecting and extracting mentions of social groups from various sources of texts, creating new possibilities for empirical research in political science.
The Chan–Robbins–Yuen polytope ($CRY_n$) of order n is a face of the Birkhoff polytope of doubly stochastic matrices that is also a flow polytope of the directed complete graph $K_{n+1}$ with netflow $(1,0,0, \ldots , 0, -1)$. The volume and lattice points of this polytope have been actively studied; however, its face structure has received less attention. We give generating functions and explicit formulas for computing the f-vector by using Hille’s (2003) result bijecting faces of a flow polytope to certain graphs, as well as Andresen–Kjeldsen’s (1976) result that enumerates certain subgraphs of the directed complete graph. We extend our results to flow polytopes of the complete graph having arbitrary (non-negative) netflow vectors and recover the f-vector of the Tesler polytope of Mészáros–Morales–Rhoades (2017).
I raise two concerns about Bergmann’s philosophical methodology: the first is a parity problem for his intuition-based “autodidactic” approach; the second is a tension between that approach and the commonsense tradition in which he situates it. I then use his approach to reflect on the limits of rational argument and set it alongside an alternative that likewise emphasizes the personal nature of philosophical inquiry while remaining more neutral about the rational standing of competing intuitions.
Joe Arroyo’s music, specifi cally his carnival compositions, generates modes of solidarity that transcend national and temporal boundaries. His “musical mechanism,” employing the clave rhythm and improvisational structures, facilitates a collective reinhabitation of the past, a redemptive challenging of colonial divisions between the living and the dead. Arroyo’s work, therefore, demonstrates the transformative power of music to forge solidarity across carnival participants.
The ability to efficiently complete everyday tasks was evaluated with a novel, performance-based test called the Virtual Kitchen Challenge (VKC) in college athletes. Analyses focused on the effect of practice and associations between the VKC and conventional measures of cognition.
Method:
81 college athletes with and without self-reported concussion completed conventional cognitive tests and the VKC, a nonimmersive virtual-reality task that requires manipulating virtual objects on a touch screen to prepare a breakfast and lunch under two conditions: 1) Training condition with feedback and 2) Test condition without feedback. VKC performance was scored for completion time, percent of time working on-screen, number of interactions with target and distractor objects. Paired t-tests compared VKC Training and Test conditions, correlations examined relations between VKC performance and cognitive tests.
Results:
VKC performance was significantly better after practice, as noted by faster completion time, fewer screen interactions, and a higher proportion of time spent on-screen during Test vs. Training conditions. Interactions with distractors were too infrequent for analyses. Correlations showed VKC Training was associated with episodic memory abilities whereas VKC Test scores were associated with executive function. VKC scores did not differ between participants with versus without concussion.
Conclusions:
The VKC is a promising portable performance-based measure of subtle functional difficulties for young, high-functioning participants. The VKC automated scoring makes it highly efficient for large studies and clinical settings.
This study examines whether Americans are more supportive of immigration when migrants share their partisan preferences. To address this question, we embedded a preregistered experiment in a nationally representative survey that was fielded the week before the 2024 US Presidential Election. The main experimental treatment provided information that some immigrant groups tend to favor Donald Trump and the Republican Party. This information reduced support for immigration among Democrats and increased support for immigration among Republicans. Our findings suggest that immigrants’ political identities impact public support for immigration. They also suggest that Trump’s apparent gains among immigrant voters in the 2024 election have the potential to reduce partisan polarization over immigration in the future.
It was found that a significant number of patients with major depressive disorder (MDD) did not respond to the treatment, leading to high ongoing costs and disease burden. The main objective of this study was to find neurobiological indicators that can predict the effectiveness of antidepressant treatment using diffusion tensor imaging (DTI). A group of 103 patients who were experiencing their first episode of MDD were included in the study. After 2 weeks of SSRI treatment, the group of patients was split into two categories: ineffectiveand effective. The FMRIB Software Library (FSL) was used for diffusion data preprocessing to obtain tensor-based parameters such as FA, MD, AD, and RD. Tract-Based Spatial Statistical (TBSS) voxel-wise statistical analysis of the tensor-based parameters was carried out using the TBSS procedure in FSL. We conducted an investigation to determine if there were notable variations in neuroimaging attributes among the three groups. Compared to HC, the effective group showed significantly higher AD and MD values in the left CgH. Correlating neuroimaging characteristics and clinical manifestations revealed a significant positive correlation between CgH-l FA and clinical 2-week HAMD-17 total scores and a significant positive correlation between CgH-r FA and clinical 2-week HAMD-17 total scores. Functional damage to the cingulum bundle in the hippocampal region may predispose patients to MDD and predict antidepressant treatment outcomes. More extensive multicenter investigations are necessary to validate these MRI findings that indicate treatment effectiveness and assess their potential significance in practical therapeutic decision-making.
This article considers the common law offences of blasphemy and blasphemous libel; the development of the Law Commission’s recommendations on offences against religion and public worship in 1985 (which ultimately led to the abolition of the offences of blasphemy and blasphemous libel in England and Wales in 2008); and proposals from various international bodies which now argue for similar reform.
Scholarship in World Englishes has been prolific over the past several decades, and today, English is accepted as the world’s ‘hypercentral’ language (de Swann 2002). Despite legitimizing varieties of English used in diverse parts of the world, however, the focus of most World Englishes scholarship has been on educated varieties of English, perpetuating the hegemony of the educated elite. Scholarship on varieties of English used by uneducated/less educated users has been neglected, even in contexts like India, where the number of less educated users of English far exceeds the educated. This paper studies the English used at the grassroots by multilingual Indians in urban India and Oman, a country with a large migrant labor population from India. This qualitative study analyses a small corpus of public and restaurant signs and WhatsApp messages produced by Indians at the grassroots levels in urban India and Oman, and focuses on categorizing the features employed to communicate (successfully). Features are categorized as orthographic, lexical, and grammatical. The study concludes with a discussion on the necessity of including English at the grassroots in World Englishes scholarship to capture the reality of the Englishes used around the world.