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In 362/363 the Roman emperor Julian composed a treatise titled Against the Galileans in which he set forth his reasons for abandoning Christianity and returning to devotion to the traditional Greco-Roman deities. Sixty years later Cyril, bishop of Alexandria, composed a response. His resulting treatise Against Julian would dwarf the size of Julian's original work and in fact serves as our primary source for the fragments of it that have survived. Julian's treatise was the most sophisticated critique of Christianity to have been composed in antiquity and Cyril's rebuttal was equally learned. The Christian bishop not only responded directly to Julian's own words but drew upon a wide range of ancient literature, including poetry, history, philosophy, and religious works to undermine the emperor's critiques of the Christian Bible and bolster the intellectual legitimacy of Christian belief and practice. This is the first full translation of the work into English.
Breakfast clubs create an opportunity for children to have a nutritious breakfast before school starts(1). Due to the perceived benefits, about 80% of schools across the United Kingdom run breakfast clubs, though this is likely to increase following the new government manifesto commitment on free breakfast provision in schools(2). Breakfast clubs are presently offered through the National School Breakfast Programme(3), charities or funded by schools’ budget(2). There is no standard model for delivery of breakfast clubs and research are limited. This study aimed to investigate how breakfast clubs are delivered, types of food provided and the benefits and constraints of delivery.
Primary schools offering breakfast clubs (n=17) across Yorkshire were visited and researchers observed and engaged with students and staff (including those involved in delivery) through participatory research. Researchers conducted interviews with 17 school leads and focus group discussions with 103 children (between 3-7 children from each school). Topic guides were developed by the research team to understand the food system within schools, including barriers to food provision, nutrition education and whole school approaches to food. The data was audio recorded and transcribed verbatim. Thematic analysis was conducted using the CONNECTS-Food principles Framework(4).
Our findings revealed that breakfast clubs provided children with an enjoyable start to the school day. The main themes developed were Type/quality of provision, Eating environment and Pastoral care. The delivery schemes varied and most schools offered places free or subsidised for children on Free School Meals (FSM) or other government schemes. Several schools considered children from disadvantaged families and offered a free breakfast regardless of FSM eligibility. Our findings revealed that there was diversity of foods on offer. However, the quality was perceived to relate to availability and price and was often dictated by providers rather than through school or child preferences. Offers commonly included bagels, cheese sandwiches, toast, cereals, milk, spreads and juice. The potential of schools to offer breakfast was key, particularly for families who do not have the resources or time to provide breakfast for their children. The eating environment was largely dependent on space and facilities; although, pleasant and supportive atmospheres were commonplace. Activities included drawing, reading books and games. We learnt about the value of breakfast clubs to create an environment with social and educational benefits. Our research specifically highlights the importance of breakfast clubs to support working parents through the childcare provision.
The findings suggest that further research is needed to investigate the adherence of the food provided to school food standards. This study is important as it provides insights into how breakfast clubs can be better delivered considering the new government’s manifesto commitment on school breakfast.
FixOurFood Project is funded by UKRI Transforming Food Systems with grant number BB/V004581/1
Lightning strike is rare, with a reported incidence of around 1:100,000. There are few reports of survival after cardiac arrest due to lightning strike. We report the case of a 12-year-old male survivor. Though he had a prolonged out of hospital cardiac arrest and initial poor systolic function, widespread ST segment elevation on electrocardiography, and elevated cardiac troponin I, he survived with a good cardiac and neurological outcome.
This study outlines design principles for a generic thermal management system (TMS) using a multi-design point approach. Four TMS configurations were analysed for a regional turboprop and short-haul type aircraft, focusing on total system gross power as an indicator of cost and environmental impact. Mechanisms were introduced to prevent coolant freezing. Results highlight the puller fan configuration as the most beneficial, leveraging temperature differentials and using the Meredith effect for increased operating capability. The ram-air configuration is slightly more efficient than the puller fan configuration for regional aircraft, but only for high system efficiencies and with operational constraints (taxiing in hot day conditions). Dual fan configurations offer significant thrust but also increased mass. The dual fan configuration shows comparable total system gross power to the puller fan for short-haul aircraft in cruise conditions, but not for regional aircraft. The pusher fan is not optimal for both aircraft types since the radiator significantly increases the heat exchanger inlet temperature, which results in higher drawbacks in terms of mass and total system gross power. In conclusion, the study emphasises the necessity to consider all relevant effects in the TMS design, such as drag, mass and efficiency, to allow the design of an optimal overall system.
Poor iron status is one of the most prevalent problems facing infants worldwide, in both developing and developed countries(1). A complex interplay of both dietary and non-dietary factors affects iron intake, absorption, and requirements, and subsequently iron status(2). We aimed to describe iron status in an ethnically diverse cohort of urban-dwelling infants. Data were collected from 364 infants aged 7.0 to 10.0 months living in two main urban centres in New Zealand (Auckland and Dunedin) between July 2020 and February 2022. Participants were grouped by total ethnicity, with any participants who did not identify as either Māori or Pacific categorised into a single ‘others’ group. Haemoglobin, plasma ferritin, soluble transferrin receptor (sTfR), C-Reactive protein, and alpha-1-acid-glycoprotein were obtained from a non-fasting venous blood sample. Inflammation was adjusted for using the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anaemia (BRINDA) method(3). Body iron concentration (mg/kg body weight) was calculated using the ratio of sTfR and ferritin. A total of 96.3% of Pacific infants were iron sufficient, defined as body iron ≥0 mg/kg body weight and haemoglobin (Hb) ≥105 g/L, compared to 82.3% of Māori and 76.0% of ‘other’ (i.e. neither Māori nor Pacific) infants. ‘Other’ infants had the highest prevalence of iron deficiency overall, with 2.8% categorised with iron-deficiency anaemia (IDA) (body iron <0 mg/kg, haemoglobin <105 g/L), 11.8% with early ‘functional’ iron deficiency (body iron <0 mg/kg, haemoglobin ≥105 g/L), and 9.4% with iron depletion (ferritin <15 µg/L, in the absence of early ‘functional’ iron deficiency and iron deficiency anaemia). For Māori infants, 3.2% and 6.5% had IDA and early ‘functional’ iron deficiency respectively, and 8.1% were iron depleted. One (3.7%) Pacific infant was iron depleted, and the remainder were iron sufficient. Plasma ferritin and body iron concentration were, on average, higher in Pacific compared to non-Pacific infants. These findings give an up-to-date and robust understanding of the iron status of infants by ethnicity, highlighting an unexpected finding that infants who are neither Māori nor Pacific may be at higher risk of poor iron status in NZ.
During nematode surveys conducted to investigate the biodiversity of plant-parasitic nematodes in Mediterranean olive groves with different management strategies (organic and conventional), a nematode population of the genus Neothada was detected in southern Spain. Application of integrative taxonomical approaches clearly demonstrated that it is a new species described herein as Neothada olearum sp. nov., also representing the first report of the genus in Spain. The new species is amphimictic, characterised by a short body (563–774 μm); cuticle widely annulated (2.5–3.0 μm); total number of body annuli 214–226; 16 longitudinal ridges giving a tessellate body surface; stylet without distinct basal knobs (9.0–11.0 μm); and tail elongate-conoid, with tip bluntly rounded. The results of molecular analysis of D2-D3 28S rRNA, ITS rRNA, partial 18S rRNA, and cytochrome oxidase c subunit 1 (COI) gene sequences support for the new species status and clearly separated from N. major and other species within Neothada. Phylogenetic analyses of ribosomal and mitochondrial markers of this study suggested that Neothada is a monophyletic genus, clearly separated from Thada.
Background: While efgartigimod usage is expected to reduce immunoglobulin (IG) utilization, evidence in clinical practice is limited. Methods: In this retrospective cohort study, patients with gMG treated with efgartigimod for ≥1-year were identified from US medical/pharmacy claims data (April 2016-January 2024) and data from the My VYVGART Path patient support program (PSP). The number of IG courses during 1-year before and after efgartigimod initiation (index date) were evaluated. Patients with ≥6 annual IG courses were considered chronic IG users. Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before and after index were obtained from the PSP where available. Descriptive statistics were used without adjustment for covariates. Results: 167 patients with ≥1 IG claim before index were included. Prior to efgartigimod initiation, the majority of patients (62%) received IG chronically. During the 1-year after index, the number of IG courses fell by 95% (pre: 1531, post: 75). 89% (n=149/167) of patients fully discontinued IG usage. Mean (SD) best-follow up MG-ADL scores were significantly reduced after index (8.0 [4.1] to 2.8 [2.1], P<0.05, n=73/167, 44%). Conclusions: Based on US claims, IG utilization was substantially reduced among patients who continued efgartigimod for ≥1-year, with patients demonstrating a favorable MG-ADL response.
Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.
Background: The complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.
Background: Meningiomas are the most common intracranial extra-axial lesion. Reports of meningioma regression exist, often in the context of known hormonal or vascular fluctuations, though very few describe complete resolution. Though rare, extra-axial mimics such as lymphoma and chloroma may also spontaneously regress. Methods: Electronic medical records were used to access patient information in accordance with our local ethics review board. Results: A 29-year-old male presenting with new onset seizures was found to have a 22.7 x 26.6 mm left temporal extra-axial lesion, radiologically consistent with meningioma. Due to wait times and patient preference, repeat pre-operative imaging was not available prior to surgical resection 13 months later, though an interim CT had confirmed persistence of the tumour’s size 1 month after diagnosis. Decision was made to proceed with resection; however, intraoperatively, no lesion was identified. Post-operative imaging demonstrated complete disappearance of the lesion, and follow-up imaging has shown no recurrence. Conclusions: This case highlights the possibility of spontaneous resolution of extra-axial lesions and emphasizes the importance of serial imaging prior to resection.
Background: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population, likely due to demyelination impacting the trigeminal pathways. While brainstem lesions are associated with MS-TN, their precise role remains unclear. Methods: This study investigates the relationship between brainstem MS plaque location, TN symptoms, and treatment response. We retrospectively analyzed brain MRIs of MS-TN patients, segmenting and coregistering brainstem plaques in MNI space. A tractographic atlas of the trigeminal system was generated using high-resolution diffusion imaging from 30 patients. Lesion involvement was determined by intersection with the trigeminal tract, and its association with pain intensity and treatment outcomes was analyzed using linear regression. Results: Our research revealed 83% of MS-TN patients had brainstem lesions near the fourth ventricle. No single lesion hot spot was identified. Lesion volume did not predict symptom recurrence or treatment response. However, 97% of lesions intersected the trigeminal tract, supporting its association with TN symptoms. Conclusions: The strong overlap between lesions and the trigeminal tract suggests a potential pain generator in MS-TN. Further research is needed to determine whether similar lesions exist in asymptomatic MS patients and to confirm this hypothesis. Future studies will explore whether tract involvement better predicts clinical response to treatment.
Background: Neck vessel imaging is often performed in hyperacute stroke to allow neurointerventionalists to estimate access complexity. This study aimed to assess clinician agreement on catheterization strategies based on imaging in these scenarios. Methods: An electronic portfolio of 60 patients with acute ischemic stroke was sent to 53 clinicians. Respondents were asked: (1) the difficulty of catheterization through femoral access with a regular Vertebral catheter, (2) whether to use a Simmons or reverse-curve catheter initially, and (3) whether to consider an alternative access site. Agreement was assessed using Fleiss’ Kappa statistics. Results: Twenty-two respondents (7 neurologists, 15 neuroradiologists) completed the survey. Overall there was slight interrater agreement (κ=0.17, 95% CI: 0.10–0.25). Clinicians with >50 cases annually had better agreement (κ=0.22) for all questions than those with fewer cases (κ=0.07). Agreement did not significantly differ by imaging modality: CTA (κ=0.18) and MRA (κ=0.14). In 40/59 cases (67.80%), at least 25% of clinicians disagreed on whether to use a Simmons or reverse-curve catheter initially. Conclusions: Agreement on catheterization strategies remains fair at best. Our results suggest that visual assessment of pre-procedural vessels imaging is not reliable for the estimation of endovascular access complexity.
Background: Adverse effects and risks associated with glucocorticoid (GC) treatment are frequently encountered in immune-mediated neuromuscular disorders. However, significant variability exists in the management of these complications. Our aim was to establish international consensus guidance on the management of GC-related complications in neuromuscular disorders. Methods: An international task force of 15 experts was assembled to develop clinical recommendations for managing GC-related complications in neuromuscular patients. The RAND/UCLA Appropriateness Method (RAM) was employed to formulate consensus guidance statements. Initial statements were drafted following a comprehensive literature review and were refined based on anonymous expert feedback, with up to three rounds of email voting to achieve consensus. Results: Consensus was reached on statements addressing general patient care, monitoring during GC therapy, osteoporosis prevention, vaccinations, infection screening, and prophylaxis for Pneumocystis jiroveci pneumonia. A multidisciplinary approach to managing GC-related complications was highlighted as a key recommendation. Conclusions: This represents the first consensus guidance in the neurological literature on GC complications, and offer clinicians structured guidance on mitigating and managing common adverse effects associated with both short- and long-term GC use. They also provide a foundation for future debate, quality improvement, research work in this area.
Haemolysis is developing prominence in the setting of supporting increasingly complex children with heart failure with a ventricular assist device. The goal of this study is to better characterise haemolysis and its implications in children supported with pulsatile ventricular assist devices.
Methods:
This is a single-centre retrospective review of 44 children who were supported by Berlin Heart EXCOR between January 2006 and June 2020. Patients were divided into major haemolysers and non-major haemolysers. Major haemolysers were defined as patients with lactate dehydrogenase > 500U/L (2.5x the upper limits of normal) with either total bilirubin > 2mg/dL (with predominantly indirect hyperbilirubinemia) or anaemia out of proportion to the clinical scenario more than three days following implantation of the ventricular assist device(s). Patient demographics, ventricular assist device factors, and outcomes, including end-organ function and mortality, were compared between major haemolysers and non-major haemolysers.
Main results:
Forty-four patients supported by the Berlin EXCOR were included in the analytic cohort of the study: 27 major haemolysers and 17 non-major haemolysers. Major haemolysis was more common in those supported with single-ventricle ventricular assist device (i.e., VAD in the context of functionally univentricular anatomy) compared to those with biventricular hearts, p = 0.01. There were no patients with an isolated left ventricular assist device or isolated right ventricular assist device in our analytic cohort of 44 patients. Of the 19 patients with single-ventricle ventricular assist device, 84% (16/19) were major haemolysers. Of the 25 patients with a biventricular assist device, 44% (11/25) were major haemolysers. Major haemolysers and non-major haemolysers had a body surface area of 0.28 and 0.40, respectively (p = 0.01). Overall, survival to discharge from the hospital was 66% (n = 29/44). Survival to discharge from the hospital was 52% (14/27) in major haemolysers versus 88% (15/17) in non-major haemolysers, p = 0.02. Only 3 of the 27 with major haemolysis had severe haemolysis, that is, lactate dehydrogenase > 2000 and bilirubin above 10. Non-major haemolysers had a better improvement in creatinine clearance during ventricular assist device support, p < 0.0001. (During the same era of this study, 22 patients who were supported with Berlin Heart were excluded from the analytic cohort because they did not have any recorded measurement of lactate dehydrogenase. Seventeen of these 22 patients had no clinical evidence of haemolysis. Survival to discharge from the hospital in this excluded cohort was 86% [19/22].)
Conclusions:
Major haemolysis in patients with pulsatile ventricular assist device is more likely with single-ventricle ventricular assist device support and smaller body surface area.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Early Miocene land mammals from eastern North America are exceedingly rare. Over the past several decades a small, but significant, vertebrate fauna has been recovered by paleontologists and citizen scientists from the Belgrade Formation at the Martin Marietta Belgrade Quarry in eastern North Carolina. This assemblage has 12 land mammal taxa, including beaver (Castoridae), stem lagomorph, carnivorans (Mustelidae, Ailuridae), horses (Equidae), rhinoceros (Rhinocerotidae), tapir (Tapiridae), peccary (Tayassuidae), anthracothere (Anthracotheriidae), entelodont (Entelodontidae), and protoceratid (Protoceratidae). Taken together, the biochronology of this Maysville Local Fauna indicates a late Arikareean (Ar3/Ar4) to early Hemingfordian (He1) North American Land Mammal Age (NALMA). This interval, which includes the Runningwater Chronofauna, documents numerous important Holarctic immigrants, including Amphictis, Craterogale, and cf. Menoceras found at this locality. Strontium isotope stratigraphy (SIS) of shark teeth collected in situ from the Belgrade Formation yield an age of 21.4 ± 0.13 Ma, which validates the age of interbedded land mammals within this unit. It also is consistent with the late Arikareean (Ar3/Ar4) biochronology and Aquitanian Neogene marine stage. New SIS analyses of oysters (Striostrea gigantissima) and clams (Chione) from this mine, previously assigned to late Oligocene or Late Miocene, are significantly older (28.0 ± 0.22 Ma and 27.6 ± 0.26 Ma, respectively) than the land mammals. Depending upon stratigraphic interpretations, these may confirm an older marine facies within the Belgrade Formation. This locality is important because of its marine and terrestrial tie-ins that facilitate intercalibration of both NALMAs and Cenozoic marine stages.