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Cognitive intra-individual variability (IIV) is a neuropsychological marker reflecting divergent performance across cognitive domains. In this brief communication, we examined whether clinical severity, apolipoprotein E (APOE) ε4 carriers, and higher polygenic risk were associated with higher cognitive IIV, and whether higher polygenic risk and cognitive IIV synergistically influence clinical severity.
Method:
This large study involved up to 24,248 participants (mean age = 72) from the National Alzheimer’s Coordinating Center (NACC) and multiple regression controlling for age, sex, and education was used to analyze the data.
Results:
We found that disease severity (B = 0.055, SE = 0.001, P < 0.001), APOE ε4 carriers (B = 0.02, SE = 0.003, P < 0.001), and higher polygenic risk (B = 0.02, SE = 0.004, P < 0.001) were associated with higher cognitive IIV. Polygenic risk and cognitive IIV also interacted to influence clinical severity, beyond APOE ε4 (B = 0.11, SE = 0.05, P = 0.02), such that individuals with high polygenic risk and cognitive IIV had the greatest clinical severity.
Conclusions:
Heightened polygenic risk and increased cross-domain cognitive variation are implicated in dementia and may impact clinical decline in tandem.
This policy brief analyzes the effects of reclassifying large swaths of the federal civilian workforce currently appointed to the competitive service into Schedule F (Policy/Career Schedule) appointments. We review the policy when it was first introduced in 2020 and reinstated with amendments in 2025. In doing so, we draw from decades of extant literature within the organizational sciences to analyze the validity of one of its main assertions, that is, moving federal workers toward at-will employment is beneficial. Our analysis shows that, as it currently stands, the proposed reclassification into Schedule F would generate widespread, chronic job insecurity and fail to improve federal workers’ performance or accountability, in addition to other physical and psychological adverse consequences. It would also result in significant, negative outcomes for federal agencies in terms of their reduced ability to attract and retain competent civil servants, lower economic efficiency, and ultimately negatively impact the customers of federal agencies by increasing costs for lower quality governmental services.
We investigated differences in cognition between variants of progressive supranuclear palsy (PSP) including PSP-Richardson (PSP-RS) and subcortical and cortical variants using updated diagnostic criteria and comprehensive neuropsychological assessment.
Method:
We recruited 140 participants with PSP (age = 71.3 ± 6.9 years; education = 15.0 ± 2.8 years; 49.3% female) who completed neurological and neuropsychological assessment. Participants received diagnoses of PSP clinical variants at their evaluation (or retrospectively if evaluated before 2017) according to the Movement Disorder Society PSP criteria. We grouped variants as PSP-RS (62 participants), PSP-Cortical (25 with PSP-speech/language and 9 with PSP-corticobasal syndrome), and PSP-Subcortical (27 with PSP-parkinsonism, 11 with PSP-progressive gait freezing, and 6 with PSP-postural instability). Analysis of covariance adjusted for age assessed for differences in neuropsychological performance between variants across cognitive domains.
Results:
PSP-Cortical participants performed worst on measures of visual attention/working memory (Spatial Span Forward/Backward/Total), executive function (Frontal Assessment Battery), and language (Letter Fluency). PSP-RS participants performed worst on verbal memory (Camden Words). There were no significant group differences for the MoCA or indices of visuospatial function. There were no sex or education differences between PSP groups; however, there were differences in age at visit and disease duration.
Conclusions:
In a large sample of participants with PSP, there were differences in cognition across PSP-RS, PSP-Subcortical, and PSP-Cortical variants, with PSP-Cortical and, to a lesser extent, PSP-RS, performing worse on tests of attention and executive function. These findings suggest cognitive distinctions among PSP clinical variants and highlight the value of neuropsychological assessment in differential diagnosis of PSP subtypes for more accurate and timely clinical classification.
Over the course of the eighteenth century, Russian rulers released dozens of decrees about petitions. First, the decrees regulated the format of petitions, emphasizing their formulaic nature and moving them away from the personal appeals with supplication and abasement that were present in earlier centuries. These decrees recognized that petitions were essential to the administrative functioning of the imperial Russian state but saw them as akin to forms or applications. Second, the decrees stated firmly that petitioners should not approach the ruler directly. In part, these decrees reflect the rulers’ irritation at being endlessly bothered by personal requests, but Russia’s rulers also gave a more serious justification for the ban on personal appeals: they had established the rule of law, which meant that their subjects did not need to bother them personally and instead should clearly know other authorities—courts, governors—to address for aid. While efforts to change the format of petitions largely succeeded, efforts to curtail petitions directly to the ruler largely failed. That failure likely reflects several factors: inefficiencies in the judicial or administrative system, contradictory laws that still made space for petitions because they were useful, and because they held the promise of getting help quickly.
An account of human subjectivity is built up from an analysis of the fundamental human desire for God. In conversation with Karl Rahner and Blaise Pascal, it is argued that this desire does not have any conceivable conditions of satisfiability. This leads to an account of human beings as fundamentally distractible, fragmented, opaque to themselves and non-self-identical; however, none of these are viewed as essentially problematic, arising instead out of the basic human–God relation rather than from a fallen condition. A range of implications for ethics and social criticism are briefly suggested.
In this paper, we initiate the study of higher rank Baumslag–Solitar (BS) semigroups and their related C*-algebras. We focus on two rather interesting classes—one is related to products of odometers and the other is related to Furstenberg’s $\times p, \times q$ conjecture. For the former class, whose C*-algebras are studied in [32], we here characterize the factoriality of the associated von Neumann algebras and further determine their types; for the latter, we obtain their canonical Cartan subalgebras. In the rank 1 case, we study a more general setting that encompasses (single-vertex) generalized BS semigroups. One of our main tools in this paper is from self-similar higher rank graphs and their C*-algebras.
Cognitive behavioural therapy for fatigue (CBT-F) and insomnia (CBT-I) are effective therapies. Little is known on their effectiveness when severe fatigue and insomnia co-occur.
Aims:
This observational study investigated whether the co-occurrence of fatigue and insomnia influences the outcomes of CBT-F and CBT-I. Furthermore, it was determined if changes in fatigue and insomnia symptoms are associated, and how often the co-occurring symptom persists after CBT.
Method:
Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS, n = 241) received CBT-F and patients with insomnia disorder (n = 162) received CBT-I. Outcomes were fatigue severity assessed with the subscale of the Checklist Individual Strength (CIS-fat) and insomnia severity assessed with the Insomnia Severity Index (ISI). In each cohort, treatment outcomes of the subgroups with and without co-occurring symptoms were compared using ANCOVA. The association between changes in insomnia and fatigue severity were determined using Pearson’s correlation coefficient.
Results:
There were no differences in treatment outcomes between patients with and without co-occurring fatigue and insomnia (CBT-F: mean difference (95% CI) in CIS-fat-score 0.80 (−2.50–4.11), p = 0.63, d = 0.06; CBT-I: mean difference (95% CI) in ISI-score 0.26 (−1.83–2.34), p = 0.80, d = 0.05). Changes in severity of both symptoms were associated (CBT-F: r = 0.30, p < 0.001, CBT-I: r = 0.50, p < 0.001). Among patients no longer severely fatigued after CBT-F, 31% still reported insomnia; of those without clinical insomnia after CBT-I, 24% remained severely fatigued.
Conclusion:
CBT-F and CBT-I maintain their effectiveness when severe fatigue and insomnia co-occur. Changes in severity of both symptoms after CBT are associated, but the co-occurring symptom can persist after successfully treating the target symptom.
As part of a larger campaign to end diversity, equity, and inclusion, President Donald Trump’s recent Executive Order 14173 eliminated EO 11246 “Equal Employment Opportunity.” In this brief, we provided background on the often-misunderstood EO 11246 and discuss the potential implications of its reversal considering previous state legislation banning affirmative action and the current political context.
Congenitally corrected transposition of the great arteries is a rare congenital cardiac condition with varied presentations, complicating treatment decisions. This study evaluates the impact of medical management, physiologic repair, and anatomic repair on health-related quality of life.
Methods:
A cross-sectional follow-up was conducted on 50 congenitally corrected transposition of the great arteries patients from a cohort of 240 at Cleveland Clinic (1995-2020). Health-related quality of life was assessed using MacNew and PROMIS-10 questionnaires. Echocardiographic data on systemic atrioventricular valvular regurgitation and systemic ventricular dysfunction were analysed. A time-varying coefficient model evaluated these factors’ impact on health-related quality of life.
Results:
Anatomic repair had significantly higher PROMIS-10 Physical T-scores compared to physiologic repair (median 50.9 vs 41.6, p = 0.04). MacNew Social scores were significantly higher for medical management compared to physiologic repair (median 6.8 vs 6.0, p = 0.02). Echocardiographic analysis revealed that systemic ventricular dysfunction had a stronger immediate impact on health-related quality of life. Systemic atrioventricular valve regurgitation showed a delayed negative effect, significant at 6-10 years after echo, although this effect gradually decreased over time. Anatomic repair patients had better systemic ventricular function (84.6% normal), and less systemic atrioventricular valve regurgitation (69.2% had none) compared to medical management and physiologic repair groups.
Conclusions:
Anatomic repair improves health-related quality of life in congenitally corrected transposition of the great arteries patients, with physiologic repair showing some gains over time. Health-related quality of life data should provide important guidance regarding treatment decisions, especially in well-balanced congenitally corrected transposition of the great arteries patients.
Intelligibility is often seen as a paradigmatic goal for overcoming epistemic oppression. Understanding oppression helps to undo structures of ignorance and to create the grounds for moral, political, and legal arguments that protect marginalized people from being silenced. This is especially crucial for those who experience sexual and gendered violence, as they often struggle both to understand their own experiences and to make others understand them. In this paper, I argue that social epistemologists and feminist standpoint theorists often focus in an unvariegated way on intelligibility, inadvertently reinforcing reliance on carceral structures—systems that tend to reproduce harm and violence for survivors. This concern is particularly relevant in feminist anti-rape politics, where the pressure to make experiences legible often intersects with calls for carceral solutions, which fail to address the root causes of harm and maintain cultures of sexual and gender violence. To remedy this, I propose a new epistemological framework that preserves the importance of intelligibility while challenging carceral reliance. Instead of focusing solely on comprehension, I suggest approaching intelligibility as a process of navigating layers of social legibility, allowing for alternatives that better support survivors and resist carceral thinking.
In the UK, some devolved governments such as in Scotland have taken a distinctive approach to implementing public service reforms. In this article, we explore the key enablers and constraints of outcome-based initiatives at the sub-national level. Drawing on a formative evaluation of the delivery of the Social Bridging Finance model, this study contributes to understanding results-oriented funding models and pluralist governance in welfare services beyond Scotland in three key ways. First, it emphasises the critical role of independent, multi-year grant funding in enabling more equitable and collaborative relationships between public bodies and the third sector. By reducing financial risk, such mechanisms challenge traditional state-led financing models. Second, it highlights the dual role of contractual agreements – supporting early sustainability discussions but revealing limitations when legal enforceability is weak. This points to the relevance of informal and relational accountability in outcome-based commissioning. Third, the study identifies the importance of collaboratively developed success criteria. The diverse experiences revealed in this study emphasise the need for flexibility, shared ownership and continuous learning – particularly given public sector responsibility for service continuity.
With the steady improvement in the efficacy of Ozaki technique in children over the past decade, it is more active and widely used in children with aortic valve disease. Ozaki technique has obvious advantages over traditional prosthetic valve replacement. It preserves the natural motion of the aortic annulus, preserves the coordination of the left ventricle, the sinus of Valsalva and the aorta, naturally dilates the aortic root during systole, restores the physiological laminar flow pattern, and retains the continuous growth potential of the aortic annulus. It has good early and mid-term valve durability, no need for anticoagulation, short learning curve time, easy to promote, suitable for a wide range of people, and significant economic benefits, especially in developing countries with serious shortage of medical resources but a large number of CHD patients. Theoretically, Ozaki techniques can be considered in patients of all ages (adults and children) and in those with acquired and congenital aortic valve disease, including those with previous mechanical, bioprosthetic, or Ross procedures. We currently support the concept of using Ozaki technique as a surgical repair method for children with severe aortic valve disease, but the specific strategy should be made individually according to the patient’s condition. This article reviews the past and present, surgical indications, surgical procedures, advantages, prognosis, and prospects of Ozaki technique in treating aortic valve disease in children.
The essay deals with the rape component of the Muslim Turkish massacres of Christian Armenians, Greeks and Assyrians during the years between 1894 and 1924 and the pertinent archival sources. During the three bouts of massacre, amounting to staggered genocides, in 1894–1896, 1915–1916 and 1920–1924, in which the Muslim Turks, under Ottoman imperial governments and, subsequently, under Ataturk’s Nationalist/republican rule, murdered some two million Christians, tens of thousands of Christian women were raped and/or forcibly abducted to Muslim households and Islamized. While almost all Turkish official records of these events have been destroyed or slicked away, archives in the West - US, German, French and British state archives and archives of missionary societies then operating in Asia Minor - are open to researchers and abound with materials that describe and analyze the massacres and the rapes and abductions that accompanied them. The essay lays out what happened and why, and how researchers have traced what happened.
Patients with familial adenomatous polyposis (FAP) have increased risk of hepatoblastoma (HB). We report monozygotic twins with HB in a FAP family. To explore genetic alterations in the HBs of the twins, we carried out whole exome sequencing (WES), RNA-seq, and immunohistochemical analyses of the tumors. Additional multiregional digital PCR was performed to profile clonality of each tumor. To determine a pathogenic germline variant in APC, Sanger sequencing was applied for the twins, the father, and the siblings of the father. A pathogenic variant of the APC gene was identified in the father as well as the twins. The WES of the HBs in the twins identified somatic mutations, including an NRAS mutation in the tumor of the first infant (C1), and an ACVR2A mutation in the tumor of the second infant (C2). No somatic mutations were identified in the genes associated with the Wnt signaling pathway. However, accumulation of β-catenin was found in the C1 and C2 tumors by immunohistochemical staining, suggesting activation of the Wnt signaling pathway. Digital PCR analysis revealed that the NRAS mutation was found in multiregional specimens of C1 and those of C2. The ACVR2A mutation was found in multiregional specimens of C2, whereas the mutation was also identified in those of C1. The existence of a shared somatic mutation may suggest that microchimerism took place in the development of HBs through the utero-placental circulatory system. Importantly, the initiation of tumorigenesis is thought to occur during the fetal period after organ development of the liver.