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This chapter investigates the significance for the succession of the Archpriest controversy, an intra-Catholic dispute between a group of secular priests and their Jesuit foes. It is shown that that the controversy was a genuinely significant aspect of the Elizabethan fin de siècle, with much to tell us about the political dynamics of the post-Reformation and the politics of incipient regime change. Robert Persons’s Conference and Memorial, and the Appellant pamphlets printed with the connivance of the English government are examined with a view to unpicking the pitch the various factions made to James VI. Catholics of all stripes are shown to have been proffering their support to the prospective Stuart king in return for a promise of toleration. Their disappointed hopes would eventuate in the Gunpowder Plot of 1605.
Cognitive difficulties, including problems with attention and executive processing, are common in major depressive disorder (MDD), and strongly predict psychosocial and occupational functioning. Impairment in sustained attention contributes to increased intra-individual variability (IIV) in reaction times observed during cognitive tasks. Understanding brain network changes associated with IIV could guide novel neuromodulation strategies targeting cognitive difficulties.
Methods
We analyzed baseline resting-state fMRI data from 209 patients with moderate-to-severe treatment-resistant MDD who participated in the BRIGhTMIND neuromodulation trial. Following a preregistered analytic protocol, we examined associations between: functional connectivity across three core brain networks (executive control, ECN; default mode, DMN; and salience network, SN); components of IIV derived from a choice reaction time task (using a three-parameter ex-Gaussian model); and functioning.
Results
Greater IIV was linked to increased ECN-DMN functional connectivity. The ECN supports top-down control and externally directed cognition, while the DMN supports internal mentation and rumination. ECN-DMN connectivity was modulated by the SN, which prioritizes salient internal and external stimuli. Higher SN-ECN connectivity was associated with lower ECN-DMN connectivity and with faster mean reaction times. Both IIV and mean reaction time predicted functioning, with poorer functioning related to a slowed and inflexible response pattern.
Conclusions
Distinct components of reaction time variability are associated with specific patterns of brain network connectivity, largely independent of mood severity. Connectivity between the salience and executive control networks may represent a promising target for neuromodulation interventions focused on cognitive deficits in MDD.
The aim of this review is to describe nutrition strategies that may help to meet the ever-increasing global demand for chicken meat in a sustainable manner. This may include decreased reliance on imported feedstuffs through replacement of imported protein (e.g., soybean meal) with locally available alternatives such as canola or grain legumes, as well as a reduction in crude protein content in feeds through a precision use of amino acids and enzymatic supplements. Challenges, opportunities and research needs associated with alternative feed ingredients are illustrated, and potential risks or benefits to the health of birds, consumers and their environment are discussed. It is concluded that the long-term sustainability of chicken meat requires a multifactorial approach that relies on improved feed formulation practices based on use of local ingredients, reduced crude protein, optimizing feed processing (e.g., particle size), and use of feed additives (e.g., enzymes, synthetic amino acids, pre-and pro-biotics) whilst considering their impact on efficiency of production as well as animal, human and environmental health.
We use new macroevolutionary rate estimates to resolve the dynamics of severe versus background extinction through the history of a major, globally distributed, Paleozoic zooplankton clade, the graptoloids. Our data span one of the “Big Five” mass extinctions, the Late Ordovician Mass Extinction (LOME), and several secondary, severe extinction events. We use cohort survivorship curves to derive both “instantaneous” rates and smoothed rates based on “natural” time-bin intervals that honor the structure of the data. We avoid the approximation of many approaches that average rate estimates within essentially arbitrary time bins.
We find that 63% of graptoloid extinctions lie within intervals classified previously as “background” extinction; only 7% lie within the LOME, and the remainder lie within the spans of 15 other secondary extinction events spread through the Ordovician and Silurian. Extinction rate magnitudes define a continuous, unimodal distribution. Background extinction in the graptoloids is not stochastically uniform but includes many more high-rate pulses than expected under a null model of uniform, memoryless extinction. Our results support the inference of pulsed extinction in the marine realm, with pulses occurring on timescales much finer than the standard age divisions of the Ordovician and Silurian periods. The LOME and secondary extinction events are not characterized by instantaneous extinction rates that are higher than so-called background. Instead, extinction events are distinguished from background by increased duration of their component, short-lived pulses of elevated extinction, and the LOME represents a protracted interval with multiple such pulses and little time for faunal recovery.
Our results are consistent with the notion that, whereas a mass or severe extinction may have an exceptional or singular initial trigger, the effects of that trigger propagate out to global-scale species loss via a complex web of processes that are common to many extinction episodes and may take significant time.
Background: After CDC and local surveillance identified an increase in Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacterales (KPC-CRE) caused by multiple organisms, an investigation was conducted at an acute care hospital. Cases clustered around an intensive care unit (ICU) and step-down unit (SDU), where wastewater plumbing was a suspected transmission source. Whole genome sequencing (WGS) was used to investigate this outbreak. Methods: A case was defined as detection of KPC-CRE or KPC (no organism cultured) from specimens collected at the hospital between 01/2019 to 10/2025. Clinical cases were identified via carbapenemase testing of CRE isolates using PCR (Xpert Carba-R) or by multiplex PCR panels and screening cases through PCR with reflex to culture. ICU sink and hopper samples and SDU sink samples were tested using selective media, MALDI-TOF, and multiplex PCR for KPC-CRE detection. Isolates underwent short and long-read sequencing. Result: Overall, 64 cases (37 clinical; 27 screening), involving 54 patients, were identified; 28 patients had ICU/SDU admissions during their hospitalization. The 52 cases with an organism identified included seven species, of which the most common were Citrobacter (26), Klebsiella (14), and Raoultella (5); 24 harbored blaKPC-2 (37.5%), 18 blaKPC-4 (28.1%), 5 blaKPC-3 (7.8%), 1 blaKPC-160 (1.5%), and 16 were not subtyped (25%). Seventeen isolates from five species carried blaKPC-2 on a 42 kb IncP6 plasmid, while ten isolates from five species carried blaKPC-4 on a 69 kb plasmid with Col440I and IncM1 replicons. Environmental sampling in 05/2025 found KPC-CRE in 10/12 sinks and 2/12 hoppers in the ICU and 1/22 SDU sinks (fig1). KPC-CRE environmental isolates were closely genetically related to the Citrobacter, Klebsiella, and Roultella clinical isolates and harbored similar KPC-carrying plasmids. Infection prevention and control (IPC) rounding identified patient items within the sink splash zone, including placing bath-in-a-bag in the sink. In 05/2025, a campaign was initiated to remove items from the splash zone, switch to chlorhexidine wipes, and implement daily use of an EPA-registered, sodium dichloroisocyanurate-based biofilm drain disinfectant product. Starting 07/2025, pouring of lipids and total parenteral nutrition down drains was stopped. While repeat environmental sampling in 6/2025 also found KPC-CRE in sink drains, no additional cases were identified in the ICU or SDU following these remediation activities (fig2). Conclusion: ICU sinks served as a reservoir for KPC-CRE, with transmission to patients. KPC-CRE persisted in drains following initial drain disinfection measures; therefore, changes in sink and splash-zone IPC practices appear to be important for interrupting transmission.
To evaluate the validity and correlates of inaccurate clinically diagnosed moderate/severe ICD-10 major depressive disorder (MDD) and psychiatric comorbidities in adult inpatients.
Methods
The multicenter Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D) study enrolled 18- to 75-year-old inpatients with MDD who underwent assessments for clinical, illness, and treatment characteristics, including the Mini-International-Neuropsychiatric-Interview (MINI). False-positive clinically MDD diagnoses were characterized via MINI. Diagnostic agreement between clinical and MINI-based psychiatric comorbidities was assessed with kappa-statistic.
Results
Among 401 patients (median age = 33.0 years; female = 57.1%), 42 (10.5%) were false positive for MDD (i.e., different primary diagnosis). Reasons for misdiagnosing MDD exclusive to false-positive cases included bipolar disorder (45.2%), subsyndromal depression (16.7%), and physical illness-related/substance use disorder (SUD)-related depression (4.8%), whereas missed diagnoses that could also occur in true-positive, MINI-based MDD patients included primary SUDs (23.8%) and primary anxiety disorders (9.5%). Among comorbidities, greatest disagreement between clinical and MINI-based research diagnoses existed for antisocial personality disorder (0% vs. 5.2%, κ =0), followed by anxiety disorders (7.5% vs. 45.1%, κ =0.17), obsessive-compulsive disorder (3.0% vs. 8.7%, κ =0.27), SUDs (11.0% vs. 28.4%, κ =0.29), eating disorders (3.5% vs. 7.2%, κ =0.39), and posttraumatic stress disorder (10.7% vs. 23.7%, κ =0.40).
Conclusions
Bipolar depression and SUDs contributed to two thirds of misdiagnosed MDD. Missed comorbidities included mostly anxiety disorders, SUDs, and PTSD. Accurate diagnostic assessment, including longitudinal history, is essential to reduce misdiagnosis and ensure guideline-based treatment for psychiatric disorders in MDD inpatients.
This paper presents a novel, independently controllable dual-polarized reconfigurable intelligent surface (RIS) unit cell for 6G upper mid-band ($7.125$–$24.25\,\mathrm{GHz}$) applications. The proposed unit cell is based on the diagonal placement of mutually orthogonal tunable radiators (loaded with varactor diodes) alongside static dual-polarized radiators. Full-wave electromagnetic simulations of the unit cell demonstrate a phase shift range of $270^{\circ}$, a maximum reflection loss of $4.5\,\mathrm{dB}$, and $61\,\mathrm{dB}$ cross-polarization isolation (XPI) within a $400\,\mathrm{MHz}$ frequency range centered at $15\,\mathrm{GHz}$. Furthermore, full-wave simulations of a $16 \times 16$ RIS panel were conducted for various reflection angles under both TE- and TM-polarized illuminations. The results demonstrate a wide-angle beam-steering capability of $\pm60^\circ$, with a maximum beam-pointing error of only $1.7^{\circ}$. The proposed RIS also exhibits accurate and stable reflection control under wide-angle excitation. A $3 \times 3$ prototype was fabricated to validate the unit cell’s performance. Measurement results agree with the simulations, yielding a $270^{\circ}$ phase shift, approximately $7\,\mathrm{dB}$ reflection loss, and $24\,\mathrm{dB}$ XPI. The proposed RIS is a promising candidate for future 6G communication systems.
Despite substantial investment in clinical and translational research, only a small proportion of evidence-based interventions are adopted and sustained in routine practice, contributing to persistent delays between discovery and population benefit. Dissemination and implementation (D&I) science is a critical discipline for addressing this gap, and the NIH Clinical and Translational Science Award (CTSA) program (established 2006) has been strategically positioned as a national infrastructure to advance D&I capacity. We conducted a national environmental scan of publicly available websites and documents from all 66 CTSA hubs (May–July 2025), using a structured extraction tool to capture D&I-specific activities across seven domains: institution and community partnerships, formal D&I organizational structures within the CTSA, consultation services, collaborative programming, training opportunities, educational offerings, and pilot funding mechanisms. Findings reveal substantial heterogeneity in D&I science activities across CTSA hubs; 45% had a formal D&I unit, 54% offered D&I consultation services, and 37% provided collaborative programming. Structured workforce development was limited: 12% offered D&I-focused training grants, 15% offered structured educational programs, and 15% provided D&I-specific pilot funding. Consultation models varied widely in scope, access, and evaluation practices. These findings demonstrate uneven development of D&I science infrastructure across CTSAs and highlight opportunities to strengthen capacity nationally.
Maternal mental health strongly influences child development and depression risk. This study investigated how positive and negative dimensions of prenatal maternal mental health differentially shape childhood depressive symptoms through cognitive mediators.
Methods
Participants were drawn from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort. Of the 1198 mother–child dyads enrolled, 523 (52.6% boys) had sufficient data for the mediation analysis. Maternal mental health at 26 weeks’ gestation was assessed using a bifactor model derived from the Beck Depression Inventory-II, State–Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale. Child language ability was measured at age 2 years with the Bayley Scales of Infant Development, executive function at age 7 years with the Behaviour Rating Inventory of Executive Function, and depressive symptoms at age 9 years with the Children’s Depression Inventory-2. Serial mediation models tested hypothesized pathways.
Results
Distinct mediation pathways emerged. Positive maternal mental health was associated with enhanced early language ability, which in turn was associated with fewer depressive symptoms in later childhood (β = −0.017, 95% CI: −0.042, −0.003). Conversely, negative maternal mental health was associated with poorer executive functioning, which in turn was associated with more depressive symptoms (β = 0.040, 95% CI: 0.016–0.077).
Conclusions
Positive and negative maternal mental health are linked to childhood depressive symptoms through distinct neurocognitive pathways. By identifying language and executive function as specific developmental mediators, our findings point to targeted and developmentally sensitive intervention opportunities to disrupt intergenerational pathways of depression.
Formal thought disorder (FTD) is a highly disabling transdiagnostic feature that impedes communication and social ties. Progress in understanding and treating FTD has been hampered by the uncertainties in its assessment.
Aims
We examined if a short 3–5min assessment of transcribed speech can capture the latent dimensions and network structure of FTD and predict functional outcomes.
Method
In a transdiagnostic sample (N = 666) with a single longitudinal follow-up over 3–12 months (n = 244), we administered the short form of the Thought and Language Index to measure eight individual features of FTD. We determined the baseline factor structure of FTD, its temporal invariance at follow-up, and the predictive validity of FTD dimensions on the global single-item Social and Occupational Functioning Assessment Scale scores at baseline and follow-up. We identified the most influential and putative primary phenomena within the FTD syndrome, using network analysis.
Results
Factor analyses revealed a stable three-factor model of FTD: impoverishment (poverty of speech, weakening of goal), loosening (looseness, illogicality) and peculiarities (peculiar words, peculiar sentences), with excellent fit (Comparative Fit Index: 0.997, root mean square error of approximation: 0.040) and metric invariance over time. Impoverishment and peculiarities predicted functioning at baseline and 3–12 months later (cross-sectional: β = –0.196, p < 0.001 and β = –0.298, p = 0.001, respectively; longitudinal: β = –0.201, p = 0.037 and β = –0.336, p = 0.042, respectively). Looseness and poverty of speech were putative primary features influencing other FTD phenomena. Weakening of goal and peculiar sentences were the most connected phenomena.
Conclusions
By integrating latent variable and network approaches, we provide a unified, empirically grounded framework to interpret FTD assessed using a brief speech task. We report a replicable three-dimensional structure, identify central symptoms that may maintain the FTD syndrome, and the specific dimensions that influence functional disability. These findings clarify the prognostically valuable features of FTD for future mechanistic and interventional research.
Objectives/Goals: To identify population-specific and ancestry-informed genetic loci for blood pressure traits, characterize X chromosome associations, and evaluate evidence for evolutionary pressures influencing blood pressure risk across ancestries, which may be used downstream clinically for personalized medicine and drug target identification. Methods/Study Population: We conducted multi-ancestry and ancestry-stratified genome-wide association studies (GWAS) of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) across >2.5M individuals (40% non-European) from 16 cohorts and biobanks. Analyses were adjusted for age, age², sex, body mass index, and the first 10 principal components. Fixed-effects meta-analyses were followed by SuSiEx cross-population fine-mapping to identify ancestry-specific loci. We evaluated genetic differentiation using the fixation index (FST) and allele frequency directionality using the sign test to infer potential evolutionary pressures. Results/Anticipated Results: Multi-ancestry meta-analyses identified 2,406 significant independent loci for SBP (1,594 novel), 2,358 DBP (1,509 novel), and 2,312 PP (1,432 novel). Chromosome X analyses revealed 8 SBP, 80 DBP, and 8 PP loci. SuSiEx fine-mapping identified ancestry-specific signals, including a pulse pressure SNP near CTSL (Asian-specific) and a DBP SNP in CACNA1D (African-specific). Sign tests indicated enrichment of DBP risk alleles when comparing African and Asian populations and when comparing Admixed American and Asian populations (p < 0.01), supported by elevated FST values for variants with larger effect sizes. These findings suggest that ancestry-specific selection may influence blood pressure regulation. Discussion/Significance of Impact: This is the largest and most ancestrally diverse blood pressure genetics study to date and one of few to include X chromosome analyses, which enabled discovery of thousands of novel and population-specific loci and revealed evolutionary and biological insights that may advance precision medicine for hypertension.
The Deep South has the highest rates of obesity, diabetes, and hypertension in the nation, with marked disparities by race, socioeconomic status, and rurality. The mission of the Forge AHEAD Center is to improve health outcomes and reduce the burden of cardiometabolic diseases across the Deep South, with a particular focus on the prevention and treatment of these chronic diseases. Forge AHEAD is unified thematically by its application of a precision public health approach across the care continuum, defined as delivering the right intervention to the right population at the right time. This approach acknowledges the importance of context and individual beliefs and preferences, as well as the need for multi-level and multi-domain interventions to achieve health improvements. The Center brings together an interdisciplinary team of investigators from 4 institutions in 3 contiguous states in the region, as well as non-academic partners to extend cardiometabolic research into real-world community and clinical settings. Given the high prevalence of cardiometabolic diseases in the Deep South and the strong research base of the partnering institutions, the Forge AHEAD Center is ideally situated to inform research, clinical care, and policy to improve health outcomes in a region of substantial need.
In Africa, bewitchment is described as a moral framework that helps individuals and societies make sense out of disease and misfortune. Numerous African belief systems attribute difficult-to-treat health problems to bewitchment, rather than a conventional medical diagnosis, especially if biomedical doctors are unable to resolve the condition. This study examines one such illness, known as xifula, in rural Limpopo Province, South Africa.
Methods:
Using convenience sampling, 95 participants (≥18 years old) were interviewed to gauge their knowledge of the condition known as xifula. Data was analysed using NVivo software.
Findings:
Xifula is a cultural concept of distress related to bewitchment. The most common symptom of xifula is swelling of the legs or hands, followed by chronic headaches. Participants noted that xifula can start as a minor ailment, but then grows into a larger problem. After a long period without healing, however, xifula can begin to represent a significant threat to the individual’s health. Nearly all participants noted that xifula cannot be treated by Western biomedical professionals and instead requires a traditional healer to treat the condition.
Interpretation:
This research highlights the importance of context-specific education about the diagnosis and treatment of common ailments, as beliefs about afflictions, their causes, and appropriate treatments suggest a need for tailored information. As biomedical and traditional healthcare currently exist as parallel, siloed structures of diagnosis and treatment in Africa, there should also be efforts to bridge the divide between the two.
Osteogenesis imperfecta (OI), colloquially known as “brittle bone disease,” must be routinely considered in all children presenting with recurrent or unexplained fractures. Proper medical work-up includes careful consideration of the history of present illness, review of growth patterns including length/ height, past medical history, family history, physical examination, radiographic and laboratory findings. For decades, OI was described as four major types categorized largely based on clinical features, but in the modern era of genomics, there is more expanded molecular diagnosis and nomenclature. In general, OI can be clinically categorized into mild, moderate, and severe forms. In unexplained fractures in infants, mild forms of OI present an important differential diagnosis to child abuse; more moderate and severe types are usually readily diagnosed based on clinical and radiographical presentation. There is a role for judicious use of genetic testing in cases where OI is a possibility. Ehlers-Danlos syndrome has been purported to cause fractures and mimic child abuse in infants and young children, but this is a flawed explanation largely manufactured for courtroom purposes. By understanding the natural history of OI versus other connective tissue disorders, and by adopting appropriate clinical strategies and evidence-based practices, multidisciplinary clinical teams enhance diagnostic accuracy and improve clinical outcomes for children in our care.
Constraining the timing, provenance and paleogeographic relationships of Cretaceous karst bauxites in the Austroalpine realm remains challenging due to their highly weathered, polygenetic nature and the general lack of datable fossils. X-ray diffraction (XRD) data show consistent boehmite–hematite assemblages in the Alpine deposits, whereas the Transdanubian bauxites (Alsópere, Iharkút) additionally contain gibbsite. Heavy mineral spectra are dominated by the ultrastable zircon–rutile–tourmaline assemblage, with subordinate kyanite, sillimanite and Cr-spinel pointing to contributions from medium- to high-grade metamorphic and ultramafic sources. Detrital zircon U–Pb spectra record mostly Proterozoic, Cadomian, Caledonian, Variscan, and Permian age components with regional contrasts. The Northern Calcareous Alps are dominated by Variscan ages, while Permian signatures are more prominent in the Transdanubian Range. Santonian (∼85 Ma) zircons at Kufstein reflect distal aeolian input from the Banatite magmatism. Zircon (U–Th)/He data reveal distinct low-temperature histories of the sources: Russbach contains a 90–75 Ma cooling signal reflecting Eoalpine metamorphic core complexes, whereas Jurassic–Early Cretaceous ages from Iharkút indicate sourcing from Upper Austroalpine units. Statistical comparisons confirm clustering among Santonian deposits but reveal heterogeneity in Albian and Turonian sites. The data indicate that Northern Calcareous Alps and Transdanubian Range bauxites formed from geographically distinct yet lithologically similar sources, with the rising central Austroalpine nappes acting as a topographic divide. The results refine the timing of bauxitization in the Alps, showing that some deposits, such as Russbach, are younger than previously thought, and that bauxitization was diachronous and largely controlled by tectonics during the Cretaceous.
Recent research suggests that maternal mood entropy, a novel measure of mood dysfunction, is associated with child outcomes. However, the link between maternal mood entropy and children’s structural brain development, and how this association may change across childhood, remains unclear. In a longitudinal study with neuroimaging data collected at ages 4.5, 6, 7.5, and 10.5 years (n = 1,498; n = 674 with neuroimaging), we examined whether maternal mood entropy is associated with children’s hippocampal and amygdala volumes over time. Mothers reported on negative mood symptoms at several assessments between ages 3 months and 4.5 years. We calculated maternal mood levels as the sum of mood symptoms and computed maternal mood entropy by applying Shannon’s entropy to the distributions of mood questionnaire responses. Maternal mood measures were not associated with amygdala volumes; however, mood entropy was directly associated with smaller hippocampal volumes at age 4.5 years and indirectly associated with smaller hippocampal volumes at 10.5 years through rank-order stability over time. These effects were present beyond the effects of socioeconomic status and intracranial volume and were specific to mood entropy, not mood levels. Our findings indicate that patterns of maternal mood are embedded in early childhood brain structure, setting the stage for subsequent neurodevelopment.
Anomalous aortic origin of the right coronary artery poses serious risks when involving high-risk features such as a long intramural course or a slit-like orifice, with demand ischaemia as the likely pathophysiology of sudden cardiac arrest. This case links sudden cardiac arrest to demand ischaemia, confirmed by cardiac MRI showing a transmural infarct in the right coronary artery territory. This is a rare case demonstrating transmural infarction in a patient with an anomalous aortic origin of the right coronary artery, as demonstrated by cardiac MRI findings.
Peter Winch (1926–1997) was one of the most important philosophers of his generation. Although best known for his work in social science and the interpretation of Ludwig Wittgenstein, he had a long-standing interest in ethics and political philosophy and was writing a book on political philosophy at the time of his death. This volume collects together Winch’s previously unpublished manuscripts on political philosophy, alongside an editorial introduction which outlines the development of his thought over the course of his life. It demonstrates the originality and enduring relevance of Winch's philosophical work to perennial issues concerning the nature and justification of political authority.