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Antimicrobial resistance is a global threat, and antimicrobial stewardship programs (ASP) are vital to curb resistance. A survey of 20 Dominican Republic hospitals revealed ASPs were absent in 50% and compliance with CDC core elements varied, highlighting significant challenges and areas of opportunity in implementing effective stewardship in resource-limited settings.
MicroRNAs (miRNAs) alterations in patients with bipolar disorder (BD) are pivotal to the disease’s pathogenesis. Since obtaining brain tissue is challenging, most research has shifted to analyzing miRNAs in peripheral blood. One innovative solution is sequencing miRNAs in plasma extracellular vesicles (EVs), particularly those neural-derived EVs emanating from the brain.
Methods
We isolated plasma neural-derived EVs from 85 patients with BD and 39 healthy controls (HC) using biotinylated antibodies targeting a neural tissue marker, followed by miRNA sequencing and expression analysis. Furthermore, we conducted bioinformatic analyses and functional experiments to delve deeper into the underlying pathological mechanisms of BD.
Results
Out of the 2,656 neural-derived miRNAs in EVs identified, 14 were differentially expressed between BD patients and HC. Moreover, the target genes of miR-143-3p displayed distinct expression patterns in the prefrontal cortex of BD patients versus HC, as sourced from the PsychENCODE database. The functional experiments demonstrated that the abnormal expression of miR-143-3p promoted the proliferation and activation of microglia and upregulated the expression of proinflammatory factors, including IL-1β, IL-6, and NLRP3. Through weighted gene co-expression network analysis, a module linking to the clinical symptoms of BD patients was discerned. Enrichment analyses unveiled these miRNAs’ role in modulating the axon guidance, the Ras signaling pathway, and ErbB signaling pathway.
Conclusions
Our findings provide the first evidence of dysregulated plasma miRNAs within neural-derived EVs in BD patients and suggest that neural-derived EVs might be involved in the pathophysiology of BD through related biological pathways, such as neurogenesis and neuroinflammation.
Diagnostic tools, such as the Mini International Neuropsychiatric Interview (MINI) 7.0.2 and the Structured Clinical Interview for the DSM-5 (SCID), aim to increase the validity and reliability of diagnostic assessment. However, these tools were created in high-income countries (HICs) with limited investigation of the psychometrics of these tools when used in low- and middle-income countries (LMICs). Thus, there is a need to examine the psychometric properties of these measures in LMICs. The present investigation aimed to examine the use of the MINI in Ethiopia, Kenya, and Uganda.
Methods
A multicountry comparison of the validity and reliability of the MINI was conducted in a study of 954 participants (n = 667 cases; n = 287 controls) with and without a psychotic spectrum disorder, defined as any psychotic or bipolar spectrum disorder for the NeuroGAP – Psychosis study. Test–retest reliability of the MINI was examined in a subset of 303 participants (n = 164 cases; n = 139 controls) from the overall sample.
Results
Results revealed the MINI and SCID provided excellent diagnostic accuracy with area under the curve (AUC) values of .91 (SE = .01) for the MINI and .95 (SE = .01) for the SCID. Positive predictive values (PPV) were the highest for the SCID (93.8%) and slightly lower for the MINI (88.7%). Reliability analyses revealed substantial agreement for psychotic and bipolar diagnostic groups.
Conclusions
Similar patterns of results were observed at the country level with a few notable differences. Limitations and future directions are discussed.
This study applies Bayesian chronological modeling to 16 new AMS radiocarbon dates on short-lived botanical remains and wood-charcoal recovered from the archaeological site Ahatsistari, a seventeenth-century Huron-Wendat village located in Simcoe County in Ontario, Canada. The modeled radiocarbon dates provide an independent time frame for understanding site phase and sequence, compatibility with historically documented events of a known date, and assessment of the socioeconomic and political influences affecting the composition of European trade good assemblages from different sites. We argue that Ahatsistari is likely Carhagouha, the principal village of the northern Attignawantan who were members of the Huron-Wendat Confederacy, and home to Samuel de Champlain and Joseph Le Caron from 1615 to 1616. In addition, Ahatsistari is contemporary with the archaeological site Warminster, which is believed to be Champlain’s Cahiagué. Radiocarbon dates from the archaeological sites of Ahatsistari, Warminster, and Ball are consistent with earlier suppositions for the beginning and end of Glass Bead Period 2 (AD 1600–1625), whereas differences in the composition of the glass trade bead assemblages speak to the prominent role of Ahatsistari in trade with the French and to variable trade relations among other early seventeenth-century Huron-Wendat villages.
The growing body of literature on corporate purpose has underscored its potential as a strategic driver for firms. However, its practical implementation remains challenging due to the concept’s multifaceted and often abstract nature. By reviewing 118 articles, this systematic literature review develops a process framework on how corporate purpose can be translated into concrete organizational strategies across three dimensions: antecedents, management, and consequences. Specifically, we identify the foundational conditions that shape a purpose statement in firms, examine how purpose is embedded and shared within them, and assess the multilevel outcomes of an effective purpose. The review highlights actionable levers to align purpose with strategy and practice, discussing how firms can implement their ‘reason why’. In doing so, the study provides contributions to better understand corporate purpose from both a theoretical and managerial perspective, within the broader field of strategic management.
Anaesthesia methods play a crucial role in ensuring the integrity of the animal during experimental studies. This study investigates the impact of two anaesthesia methods, CO₂ and cold treatment, on an insect antennal response to synthetic alarm pheromone compounds. Adult worker hornets were anesthetised, and their antennae excised and tested using an electroantennography set-up with controlled stimulation of alarm pheromone components. Results showed that CO₂-anesthetised hornets exhibited robust antennal responses, while cold-anesthetised individuals displayed none. This result suggests that freezing may impair the functionality of olfactory receptors. In contrast, CO₂ anaesthesia preserves receptor integrity, offering reliable and interpretable results. This study highlights the importance of selecting appropriate anaesthesia techniques to avoid artefacts in insect sensory physiology research and underscores the ecological relevance of studying Vespa velutina nigrithorax alarm signalling.
Identifying key areas of brain dysfunction in mental illness is critical for developing precision diagnosis and treatment. This study aimed to develop region-specific brain aging trajectory prediction models using multimodal magnetic resonance imaging (MRI) to identify similarities and differences in abnormal aging between bipolar disorder (BD) and major depressive disorder (MDD) and pinpoint key brain regions of structural and functional change specific to each disorder.
Methods
Neuroimaging data from 340 healthy controls, 110 BD participants, and 68 MDD participants were included from the Taiwan Aging and Mental Illness cohort. We constructed 228 models using T1-weighted MRI, resting-state functional MRI, and diffusion tensor imaging data. Gaussian process regression was used to train models for estimating brain aging trajectories using structural and functional maps across various brain regions.
Results
Our models demonstrated robust performance, revealing accelerated aging in 66 gray matter regions in BD and 67 in MDD, with 13 regions common to both disorders. The BD group showed accelerated aging in 17 regions on functional maps, whereas no such regions were found in MDD. Fractional anisotropy analysis identified 43 aging white matter tracts in BD and 39 in MDD, with 16 tracts common to both disorders. Importantly, there were also unique brain regions with accelerated aging specific to each disorder.
Conclusions
These findings highlight the potential of brain aging trajectories as biomarkers for BD and MDD, offering insights into distinct and overlapping neuroanatomical changes. Incorporating region-specific changes in brain structure and function over time could enhance the understanding and treatment of mental illness.
The current administration has disproportionately targeted transgender, nonbinary, and gender nonconforming people, despite accounting for less than 1% of the population (Jones, 2024). Though there has been a flurry of executive orders issued restricting the rights of this population, Executive Order 14168 (i.e., Defending Women from Gender Ideology Extremism and Restoring Biological Truth to the Federal Government) and Executive Order 14151 (Ending Radical and Wasteful Government DEI Programs and Preferencing) are likely to be particularly impactful for workplaces. This is because Executive Order 14168 challenges the existing federal protections of the Civil Rights Act of 1964 extended through Bostock v. Clayton County (2020), by declaring sex as binary and biological and denying the existence of transgender people. In addition, EO14151 eliminates federal diversity, equity, and inclusion programs and practices, which limits organizational practices and policies that might otherwise create inclusive and equitable environments for transgender employees. Therefore, this policy brief aims to discuss these executive orders, the existing protections they aim to alter, and the potential implications for transgender employees, organizations, and industrial-organizational professionals.
The study of the ground surface temperature (GST) regimes from 2007 to 2021 at different stations on Livingston and Deception islands, South Shetland Islands, in the north-western sector of the Antarctic Peninsula (AP), shows that soils undergo similar cooling in early winter before a shallow snow mantle covers the sites. All monitoring sites along the study period go through seasonal phases of cooling, attenuation, insulation, fusion and zero curtain during winter, although thermal equilibrium is only reached at some stations located at lower elevations on Livingston Island. GST evolution at these stations and the duration of snow periods show oscillations, with turning points in the years 2014 and 2015, when temperatures were at their minimum and snow durations were at their maximum, in agreement with the cooling period occurring in the north-western AP in the early twenty-first century. The thermal regime is mainly controlled by snow cover and its onset and offset dates based only on descriptive patterns, not on statistical testing, more than by altitudinal, topographical, geological or geomorphological factors.
This paper examines how public demand and institutional contexts shape the substantive representation of LGBTQ+ populations across Europe. I argue that while positive social constructions of LGBTQ+ populations are a necessary condition for the advances of LGBTQ+ rights, issue salience can facilitate LGBTQ+ rights only if public opinion on LGBTQ+ is positive. Furthermore, I assert that translating social constructions of LGBTQ+ populations into policy outputs is mediated by the proportionality of electoral systems. I analyze policy scores, public attitudes, and online interest concerning LGBTQ+ topics. I find that positive social constructions are correlated with more inclusive LGBTQ+ rights across countries, and the positive impact of issue salience on LGBTQ+ rights is observed only in countries with positive social constructions. Additionally, the analysis of electoral systems provides mixed evidence regarding the role of proportionality.
The present study documents the lithostratigraphy, biostratigraphy, facies evolution and depositional environments of the Eocene El Kohol Formation exposed on the southern flank of the Central Saharan Atlas (Algeria), through the integration of lithological characteristics, fossil and ichnofossil assemblages, and microfacies analysis. The succession is subdivided into two formal members: the Marly El Kohol Member, comprising a lower marlstone-dominated interval, and the Siliciclastic Kheneg ed Dis Member, representing an upper sandstone-dominated succession. The boundary between these members is marked by a transition from pale, carbonate-rich deposits to darker clastic sediments.
Field observations and microscopic analyses have enabled the recognition of sixteen facies types (Ft1–Ft16), which are interpreted in terms of depositional environment and grouped into four main facies associations (FA1–FA4): (FA1) an inland lake environment; (FA2) a palustrine environment, characterized by carbonate deposition in freshwater to brackish conditions with subaerial exposure and paedogenic modification; and alluvial settings comprising (FA3) fluvial channel and (FA4) floodplain deposits.
Palaeontological analyses have produced new micropalaeontological data for the region, including charophytes (Sphaerochara parvula, Nodosochara [Turbochara] sp., Gyrogona sp., Harrisichara cf. leptocera, Lamprothamnium papulosum, Peckichara torulosa var. varians, Raskyella cf. sahariana and Nitellopsis cf. [Tectochara] dutempleii), ostracods (Neocyprideis meguerchiensis, Paracypris? sp. 1, Paracypris? sp. 2 and Thalassocypria? sp. 1) and actinopterygian fish microremains (primarily from polypterids and alestids). Additionally, fragmentary remains of the terrestrial proboscidean Numidotherium koholense have been recovered. Ichnological analysis of the succession identified five ichnotaxa: Ophiomorpha isp., Palaeophycus isp., Skolithos annulatus, Skolithos linearis and Thalassinoides horizontalis.
This study contributes to refining the regional and North African understanding of the spatial extent and palaeoenvironmental evolution of the Eocene succession and helps to complete the ichnological and palaeontological records of the Eocene in the area.
We consider the Perron–Frobenius operator defined on the space of functions of bounded variation for the beta-map $\tau _\beta (x)=\beta x$ (mod $1$) for $\beta \in (1,\infty )$, and investigate its isolated eigenvalues except $1$, called non-leading eigenvalues in this paper. We show that the set of $\beta $ such that the corresponding Perron–Frobenius operator has at least one non-leading eigenvalue is open and dense in $(1,\infty )$. Furthermore, we establish the Hölder continuity of each non-leading eigenvalue as a function of $\beta $ and show in particular that it is continuous but non-differentiable, whose analogue was conjectured by Flatto, Lagarias and Poonen in [The zeta function of the beta transformation. Ergod. Th. & Dynam. Sys.14 (1994), 237–266]. In addition, for an eigenfunctional of the Perron–Frobenius operator corresponding to an isolated eigenvalue, we give an explicit formula for the value of the functional applied to the indicator function of every interval. As its application, we provide three results related to non-leading eigenvalues, one of which states that an eigenfunctional corresponding to a non-leading eigenvalue cannot be expressed by any complex measure on the interval, which is in contrast to the case of the leading eigenvalue $1$.
Increasing senior leadership diversity and decentralizing decision-making have become imperatives for many organizations, supported by a growing normative literature. However, mixed empirical evidence suggests that these may hinder the decision-making processes required to deliver value to firms and their stakeholders. We argue that diversity and decentralization should instead be viewed as means of organizing towards these ends, and theorize the conditions under which they may harm performance – specifically, the nature of the knowledge problems faced by leaders. Analyzing a 19-year panel of 922 U.S. firms, we find that diversity and decentralization are associated with stronger financial and market performance in uncertain environments but become liabilities under ambiguity, where speed and strategic clarity are critical and homogeneous, centralized leadership is more effective. Stakeholder outcomes are similarly affected, particularly employee wellbeing and ethical political activity. These findings challenge normative claims, with implications for theory, proscriptions, and practice.
In the first decades of the twentieth century, the concept of “direct action” emerged as a major presence in radical politics. In the years following World War I, opponents of war and militarism reshaped that concept. They insisted upon its nonviolent character, they specified how direct action might be used to oppose war, they distinguished direct action from Bolshevism and social democracy, they imagined direct action as a key contributor to a future nonviolent revolution, and they drew upon contemporary struggles from the Ruhr, to Samoa, to India to justify their political claims. The radicals who shared these debates were linked by an energetic transnational network, spanning the War Resisters’ International and the International Antimilitarist Bureau. This article recovers this network, traces the key intellectual contributions, and argues for their significance. It aims to contribute to the intellectual histories of direct action and of nonviolence and to draw attention to previously submerged debates of the radical interwar left.
To evaluate clinical outcomes in patients with uncomplicated β-hemolytic Streptococcus spp. bloodstream infections (BSI) transitioned to oral antimicrobial therapy (OAT) compared with those that remain on intravenous antimicrobial therapy.
Design:
Retrospective cohort study.
Setting:
Tertiary academic hospital.
Methods:
This retrospective cohort study included adult patients hospitalized between 1/1/2013 and 12/31/2019 diagnosed with uBSI due to β-hemolytic streptococci. Patients were excluded if BSI was due to endovascular, central nervous system, or bone/joint infection or patient was immunosuppressed or died within 72 hours of identification of BSI. We compared outcomes including: 30-day mortality, antimicrobial therapy, BSI relapse, 30-day rehospitalization, adverse drug events, and reversion to IV therapy. Fisher’s exact test was used for categorical variables; Mann – Whitney test and Independent T-test for continuous variables.
Results:
232 BSIs were included. OAT was used in 152 (65%). Cohort demographics were similar. Mortality was also similar between cohorts (2% vs 6% P = .13). Hospital length of stay was shorter in the OAT cohort with a median of 5 days (interquartile range 4.00, 8.00) versus 8 (5.00, 16.00) in the IV group (P < .0001). Patients transitioned to OAT were more likely to finish antibiotics outpatient (93% vs 62% P < .001).
Conclusion:
For β-hemolytic Streptococcus uBSI, OAT was associated with decreased length of stay without adverse clinical outcomes. Opportunities exist to modify clinical management of uBSI.
Number systems are shared social technologies. They are heterogeneous, differing along dimensions of modality, base, and marking. These characteristics impart differential advantages depending on purpose and context, which explains why most cultures employ multiple number systems simultaneously. Number systems are embedded in patterns of complementarity involving both human and physical capital. Viewing number systems this way allows us to apply economic insights about production, cost, and technology to things often regarded as purely abstract cognitive conventions. Combining these insights with the literature on 4E cognition shows how concrete economic factors can shape key aspects of how humans think.
We strengthen known results on Diophantine approximation with restricted denominators by presenting a new quantitative Schmidt-type theorem that applies to denominators growing much more slowly than in previous works. In particular, we can handle sequences of denominators with polynomial growth and Rajchmann measures exhibiting arbitrary slow decay, allowing several applications. For instance, our results yield non-trivial lower bounds on the Hausdorff dimensions of intersections of two sets of inhomogeneously well-approximable numbers (each with restricted denominators) and enable the construction of Salem subsets of well-approximable numbers of arbitrary Hausdorff dimension.