A growing number of studies has contributed to our understanding of the different roles that Sayyids (descendants of the Prophet Muḥammad) played in many regions of the Muslim world. Still, many lineages remain unexplored and especially the socio-economic roles of Sayyids often remain unclear. This article studies the little-known Sayyid al-Ḥasan b. ʿAlī from tenth-/sixteenth-century Medina, his genealogical writings, and those of one of his sons—Zayn al-Dīn ʿAlī—to trace the political rise and increasing economic affluence of their family, the Banū Shadqam. They combined their Ḥusaynid descent with the prestigious office of custodian (mutawallī) of the Prophet’s Mosque in Medina and political leadership of the Medinese Sayyids (naqīb al-ashrāf). Marital relations with the Niẓāmshāhī Dynasty in the western Deccan and scholarly services at its court in Ahmadnagar provided them with significant royal patronage. Al-Ḥasan increasingly served as socio-economic intermediary in channelling charitable donations from the Deccan to Medina. The mutually beneficial relationship between charismatic and royal authority allowed the Banū Shadqam to advance their social position among the many Sayyid families in Medina. Transgenerational practices of writing genealogical texts served to legitimise their Sayyid claims, complementing transregional mobility and royal patronage to consolidate their social and political position ‘at home’.

Psychiatry on call occupies a distinct and formative space within mental health services, shaped by moments of uncertainty, responsibility, and relational decision-making. In Ireland, non-consultant hospital doctors continue to deliver the majority of out-of-hours emergency psychiatric care, often as the sole on-site psychiatric clinician, working across multiple settings and managing high levels of clinical and organisational risk. This paper situates contemporary psychiatry on call within its wider clinical, societal, and service context, drawing on the College of Psychiatrists of Ireland’s 2025 position paper and emerging evidence on emergency mental health care. We argue that emergency psychiatry differs from other acute specialties, being characterised by distress rather than disease, uncertainty rather than diagnosis, and time-intensive relational work rather than protocol-driven intervention. Rising demand reflects broader systemic pressures, including unmet social need, reduced inpatient capacity, uneven crisis alternatives, and increasing regulatory burden. We examine the service-user experience of out-of-hours care, highlighting issues of environment, equity, trust, and safety, particularly for marginalised groups. While high-quality supervision and training remain essential, we contend that sustainable improvement requires system-level reform, including strengthened multidisciplinary crisis responses, clearer role delineation, and coordinated investment in and also beyond mental health services. Attending to psychiatry on call offers a critical lens through which to understand and improve emergency mental health care for both clinicians and service users.

Parental diet has emerged as a critical factor in programming offspring's metabolic health, yet the independent and combined effects of maternal and paternal obesogenic exposures remain largely underexplored(1, 2). In Aotearoa New Zealand, obesity affects around one in three adults and one in eight children, disproportionately burdening Māori and Pacific communities(3). Understanding how both parents contribute to offspring metabolic health is key for preventive strategies. Growing evidence suggests that increasing omega-3 intake can improve metabolic programming, offering a potential means to mitigate early obesogenic effects. Building on earlier findings of altered birth weight, this study examined adult offspring metabolism. The objective was to assess maternal, paternal, and combined obesogenic (OB) diet exposures on offspring energy metabolism and skeletal muscle citrate synthase (CS) activity, and to evaluate whether early-life omega-3 treatment could act as a rescue intervention. Male (pat) and female (mat) Sprague Dawley rats received either a control diet (CON) or OB diet for five weeks pre-mating. Females remained on their diets throughout pregnancy and lactation. Four parental diet groups were established: 1-matCON-patCON, 2-matCON-patOB, 3-matOB-patCON, and 4-matOB-patOB. Offspring from each group received either omega-3 or placebo from postnatal day (PN) 21-63. Indirect calorimetry at PN145 measured 24-h energy expenditure (EE) and respiratory exchange ratio (RER), and dark/light phase ratios were calculated to assess patterns of metabolic variation. CS activity was assessed in skeletal muscle at PN180. Statistical analysis was performed using one-way and two-way ANOVA with sex and treatment as factors. In females, offspring from 4-matOB-patOB parents showed reduced EE dark/light ratios compared with 1-matCON-patCON (p = 0.003) and 3-matOB-patCON (p = 0.04), indicating impaired metabolic flexibility. Early-life omega-3 intervention restored this EE variation in 4-matOB-patOB females, suggesting a protective effect. In males, EE ratios were reduced in 4-matOB-patOB compared with 2-matCON-patOB (p = 0.02) and 3-matOB-patCON (p = 0.04), and RER phase shifts were absent, reflecting disrupted substrate switching. Omega-3 rescued this RER rhythmicity in males but increased RER ratios in 3-matOB-patCON offspring (p = 0.04), highlighting context-dependent responses. CS activity was reduced in omega-3 treated males from 1-matCON-patCON parents (p = 0.04), pointing to potential adverse effects in low-risk backgrounds. Together, these outcomes demonstrate sex-specific programming, with males being more vulnerable to disrupted substrate switching, whereas females showed greater responsiveness to omega-3 rescue. These findings demonstrate that parental OB diets impair offspring EE and RER in a sex- and context-dependent manner, reflecting disrupted dark/light metabolic regulation. This disruption may represent an early pathway by which parental diet programs later metabolic disease risk. Early-life omega-3 provided targeted rescue but carried risks in low-risk settings, underscoring the need for tailored interventions and highlighting the importance of including both parents in strategies to break the cycle of obesity.

We describe the latest iteration of upgrades (designated Phase III) to the Murchison Widefield Array (MWA), in the fourth paper in a series that covers the evolution of the telescope from design concept to initial operational facility, and through two major upgrades. As part of the Phase III upgrade of the MWA, we report the completion of work to design, build, and deploy a new fleet of digital receivers that further optimise the MWA for Epoch of Reionisation observations. These receivers complement existing receivers, such that the MWA now supports the full correlation of all 256 antenna tiles currently in the array. This step releases the MWA from the prior constraint of having to correlate only 128 of the 256 tiles at any given time, which means that the maximum instantaneous sensitivity of the MWA is doubled and the maximum number of interferometric baselines is approximately quadrupled. The upgrade is fundamentally enabled by the new MWAX correlator and various other improvements to the MWA sub-systems. In this paper we describe the new digital receivers and the other improvements that result in the Phase III system. A range of operational benefits arise from the upgrade and scientific flexibility is increased. We also comment on the transition from the MWA to the SKA-Low facility near the end of the decade, including a description of some unique science opportunities utilising joint MWA/SKA-Low data during the Science Verification phase of the SKA-Low Array Assembly 2 (AA2) period.

Background: Penicillin allergies are common, reported in roughly 10% of the U.S. population, but fewer than 1% have a true IgE-mediated allergy. Penicillin allergy labels are associated with increased use of broad-spectrum antibiotics, higher healthcare costs, and the development of antimicrobial resistance. Antibiotic stewardship efforts have focused on identifying and de-labeling individuals without a true penicillin allergy. To date, most penicillin allergy de-labeling initiatives have been implemented in acute-care settings, where time constraints and clinical acuity may limit feasibility. Long-term care facilities represent a unique opportunity for penicillin allergy de-labeling, as residents often have prolonged stays and are less acutely ill. Previously, we found that 14% of residents admitted to the Veterans Affairs (VA) Community Living Center (CLC) in Vancouver, Washington had a documented allergy to a penicillin-class antibiotic. Here, we describe design and implementation of a penicillin allergy de-labeling program at a VA CLC and highlight opportunities for multidisciplinary collaboration. Methods: This antibiotic stewardship initiative was developed through collaboration between the VA Portland antimicrobial stewardship team and CLC providers, including physicians, nursing staff, and pharmacy. A standardized protocol was created to identify residents eligible for penicillin allergy evaluation and to outline steps for a direct oral challenge (Figure 1). At admission, CLC providers are instructed to identify residents with electronic health record (EHR) documentation of a penicillin class allergy and complete a structured allergy screening questionnaire. Residents with antibiotic intolerance alone (e.g., nausea and vomiting) receive education, and the penicillin allergy is removed from the EHR. Residents who require and agree to further evaluation are referred via electronic consult to the infectious diseases team, who verifies eligibility to undergo a direct oral challenge. CLC pharmacists review resident medications for any contraindications to performing a challenge, including receipt of medications that would reduce the histamine response. Eligible residents undergo a direct oral amoxicillin challenge with a single 500-mg dose and are monitored by nursing staff for 60 minutes. Patients without evidence of reaction receive education, and the penicillin allergy is removed from the EHR. Planned Evaluation: Planned outcome measures include completion of allergy screening, de-labeling based on chart review alone, eligibility for and completion of oral challenge, challenge outcome, and impact on subsequent antibiotic prescribing. Conclusion:This initiative describes a structured, reproducible framework for implementing penicillin allergy de-labeling in a VA post-acute care setting. The program has the potential to improve antibiotic selection and strengthen antimicrobial stewardship in skilled nursing facility (SNF) enviornments.

Objectives/Goals: To investigate how distinct KRAS mutations (G12D, G12V, and G12R) drive distinct molecular and phenotypic programs in pancreatic tumorigenesis, linking early lineage and signaling differences to clinical patterns such as stage at diagnosis, nodal status, and survival to ultimately inform allele-specific therapies. Methods/Study Population: We analyzed clinical cohorts (MSK-IMPACT n=1,360; COMPASS n=100) and conducted lineage-tracing studies in mice carrying KRAS-G12D, KRAS-G12V, or KRAS-G12R alleles under inflammatory, genetic, and pharmacologic perturbations. Spatial transcriptomic and proteogenomic profiling of resected PDAC tissues characterized EMT and immune signaling states. Functional studies assessed EGFR–PI3K/AKT–RAC1/VAV1 signaling, including RAC1 inhibition and constitutive AKT activation, to reveal allele-specific susceptibilities. Results/Anticipated Results: KRAS-G12D drove robust lineage plasticity, enhancer remodeling, and early neoplastic progression. KRAS-G12R/V showed limited EMT and increased inflammatory signatures, with impaired EGFR–RAC1/VAV1 activation restricting lineage reversion. Constitutive AKT activation rescued the tumor-initiating defect of KRAS-G12R in vivo, pinpointing a downstream signaling bottleneck, which could be exploited therapeutically. Spatial and transcriptomic profiling of resected human PDAC revealed that KRAS-G12R tumors were more often early-stage, node-negative, and linked to improved survival relative to KRAS-G12D. Discussion/Significance of Impact: Integrating patient and mouse data reveals a mechanistic hierarchy among KRAS alleles that governs lineage fate, signaling reliance, and clinical course, pointing to opportunities for allele-tailored therapeutic strategies in pancreatic cancer.

We derive the asymptotic solution for the onset of steady, linear, Boussinesq convection in a rapidly rotating system with stress-free, fixed-flux boundary conditions. While the fixed-temperature (FT) case is attainable analytically with relative ease, the fixed-flux (FF) configuration presents greater complexity. However, in the rapidly rotating limit, the leading-order interior solution remains unaffected by the choice of thermal boundary conditions. We exploit this property by employing an asymptotic approach to characterise the differences between the FT and FF systems. Specifically, this involves constructing a composite boundary layer structure comprising an Ekman layer of thickness $ {\textit{Ta}}^{-1/4}$, where $ \textit{Ta}$ is the Taylor number ($ \textit{Ta} \gg 1$ for rapid rotation), and a thermal boundary layer of thickness $ {\textit{Ta}}^{-1/6}$, to accommodate the FF boundary condition. To capture both scales systematically, we introduce the small parameter ${\varepsilon } = {\textit{Ta}}^{-1/12}$, representing the ratio between the two boundary layer thicknesses, and use it to guide the asymptotic expansion. The asymptotic corrections capturing the differences between the two systems are combined with the FT system to construct the corresponding solution for the FF system. We find an asymptotic correction of ${\mathcal{O}} ( {\textit{Ta}}^{-1/2} )$ to the critical Rayleigh number, corresponding wavenumber, vertical velocity and temperature, along with a correction of ${\mathcal{O}} ( {\textit{Ta}}^{-1/6} )$ to the vertical vorticity.

Radiocarbon dating is essential for establishing robust chronologies in archaeological and paleoenvironmental contexts spanning the last 55,000 years. Pottery, pervasive in the archaeological record, offers a crucial framework for dating human activity during the Holocene. Traditionally, radiocarbon dating of pottery has relied on targeting carbonaceous inclusions such as organic temper or measuring stratigraphically associated materials like bone and charcoal. Inaccuracies can arise, however, if the targeted fraction does not reflect the timing of vessel use or if stratigraphic associations are uncertain. An alternative involves radiocarbon dating of lipid residues, particularly fatty acids absorbed into the ceramic matrix during the processing and storage of plant and animal-derived resources. This approach holds promise for delivering highly accurate measurements directly correlating to vessel use. At the Oxford Radiocarbon Accelerator Unit, efforts have been made to develop this methodology through compound-specific radiocarbon dating of pottery, employing a gas chromatography (GC)-preparative fraction collector (PFC) approach. Here, we describe the protocol and present preliminary findings, including analyses conducted on pottery samples sourced from an archaeological site with an established chronology.

Hosking & Schekochihin (Phys. Rev. X, 2021, vol. 11, 041005) have proposed that statistically isotropic decaying magnetohydrodynamic turbulence without net magnetic helicity conserves the mean square fluctuation level of magnetic helicity in large volumes – or, equivalently, the integral over space of the two-point correlation function of the magnetic-helicity density, denoted $I_{\!H}$. Formally, the conservation and gauge invariance of $I_{\!H}$ require the vanishing of certain boundary terms related to the strength of long-range spatial correlations. These boundary terms represent the ability (or otherwise) of the turbulence to organise fluxes over arbitrarily large distances to deplete or enhance fluctuations of magnetic helicity. In this work, we present a theory of these boundary terms, employing a methodology analogous to that of Batchelor & Proudman (Philos. Trans. R. Soc. A, 1956, vol. 248, p. 369) to determine the relevant asymptotic forms of correlation functions. We find that long-range correlations of sufficient strength to violate the conservation of $I_{\!H}$ cannot develop dynamically if the evolution equation for the magnetic vector potential is chosen to be local in space. Likewise, we find that such correlations cannot develop for a wide class of gauge choices that make this equation non-local (including the Coulomb gauge). Nonetheless, we also identify a class of non-local gauge choices for which correlations that are sufficiently strong to violate the conservation of $I_{\!H}$ do appear possible. We verify our theoretical predictions for the case of the Coulomb gauge with measurements of correlation functions in a high-resolution numerical simulation.

The American Society of Clinical Psychopharmacology convened a 45-member international expert task force to identify circumstances supporting the deprescribing of core psychotropic medications for major depressive disorder (MDD) and bipolar disorders. Three Delphi survey rounds plus a selective literature review identified points of consensus (predefined as ≥75% agreement) about when antidepressant, antipsychotic, mood stabiliser and sedative-hypnotic deprescribing is warranted. Twenty out of 32 statements (63%) achieved consensus across seven thematic areas. In MDD, panellists favoured discontinuing antidepressants when mechanisms of action are duplicative, adequate trials produce ≤25% improvement or loss of prior efficacy cannot be regained through dose increases or augmentations. Indefinite antidepressant maintenance in MDD was favoured after three or more lifetime episodes. In bipolar disorder, antidepressant deprescribing was favoured in the setting of rapid cycling, mixed features or emerging mania/hypomania symptoms; and discouraged if prior antidepressant cessation led to relapse. In nonpsychotic mood disorders, panellists favoured deprescribing antipsychotics that caused significant weight gain or tardive dyskinesia over adding pharmacological antidotes. Deprescribing to achieve an eventual medication-free status was considered inappropriate, in bipolar type 1, but not necessarily bipolar type 2 disorder. Although individualised circumstances necessarily inform psychopharmacology management, clinical presentations that misalign with existing pharmacotherapies may signal the desirability of cautious deprescribing.