[89Zr]Zr-girentuximab for PET-CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial.

BACKGROUND: With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. 89Zr-labelled monoclonal antibody ([89Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [89Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma. METHODS: ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [89Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [89Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [89Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment. FINDINGS: Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [89Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [89Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths. INTERPRETATION: Our results suggest that [89Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing. FUNDING: Telix Pharmaceuticals.

Temperature dependent sensitivity of the harpacticoid copepod Nitokra spinipes to marine algal toxins.

Harmful algal blooms (HABs) - proliferated algae densities, often producing toxins - have increasingly been found in ocean and coastal areas. Recent studies show that rising temperatures contribute to HAB occurrence, but the broader influence of climate change on these outbreaks is less quantified. Of particular concern is the limited research on HAB toxin effects under varying temperatures, especially regarding primary consumers such as copepods, a crucial component of aquatic ecosystems. Therefore, we examined the impact of marine toxins on the harpacticoid copepod Nitokra spinipes, a model organism for marine ecotoxicology, in the context of climate change. We evaluated the toxicity of four purified, commonly occurring algal toxins, at three different temperatures in the laboratory. First, adult females were exposed to a concentration series of toxins at 15, 20, and 25 °C for 48 h. EC50 values of domoic acid ranged from 8.79 ± 1.93 µg L-1 to 25.97 ± 11.96 µg L-1. Nauplii, aged 48-72 h, were exposed at 18, 20 and 22 °C for the same duration. Less sensitive compared to adults, the EC50 of domoic acid in this case varied from 57.26 ± 6.82 µg L-1 to 97.24 ± 6.45 µg L-1. Both results indicated a temperature-dependent EC50. For the chronic toxicity tests, larval development ratio (LDR), brood size and inter-brood time of domoic acid (DA), yessotoxin (YTX), saxitoxin (STX), and microcystin-LR (MC-LR) were examined at 18, 20 and 22 °C. We observed that with increasing temperatures, LDR increased, whereas brood size significantly decreased as DA, YTX or STX concentrations rose. No interaction between temperature and algal toxins was found but a temperature dependent sensitivity of copepods towards DA, YTX and STX was revealed. Our research provides insights into the effects of long-term exposure to algal toxins on marine copepods and the potential impacts of climate warming.

Translation and validation of the Czech Partner version of the Birth Satisfaction Scale-Revised (BSS-R).

BACKGROUND: The Birth Satisfaction Scale-Revised (BSS-R) is a widely used, psychometrically robust and brief self-report measure of birth experience from the mothers perspective. The current study sought to adapt and validate the BSS-R for partners, evaluating key psychometric properties, including the underlying tri-dimensional factor structure of stress experienced, personal attributes and quality of care. AIM: To translate and validate a Czech speaking partner version of the Birth Satisfaction Scale-Revised (BSS-R) and examine key measurement characteristics and association with fundamental clinical outcome variables. METHOD: Following translation of the UK partner BSS-R into Czech, the Czech Partner BSS-R (CZP-BSS-R) was administered to 225 partners of women who had given birth within the past 5-years. Key psychometric characteristics were examined, including factor structure, divergent and known-groups discriminant validity and internal reliability. RESULTS: Established measurement models of the BSS-R observed in mothers were found to offer an excellent fit to partner data. The CZP-BSS-R also demonstrated excellent validity and reliability characteristics. CONCLUSIONS: The CZP-BSS-R was found to be valid and reliable, with results from Czech partners 'mirroring' factor structure and key validity characteristics previously established in Czech mothers. The BSS-R validated for completion by Czech speaking mothers now has a matched version available for use with Czech speaking partners.

Effectiveness of COVID-19 vaccines against hospitalisation, death and infection over time in Aotearoa New Zealand: a retrospective cohort study.

AIMS: This study aimed to evaluate the effectiveness of COVID-19 vaccines in preventing COVID-19 outcomes when the Omicron variant was predominant in Aotearoa New Zealand. METHODS: We conducted a retrospective cohort study using routinely available data (8 December 2020-28 February 2023). We evaluated the vaccine effectiveness (VE) of COVID-19 vaccines using the Cox proportional-hazards model, adjusting for covariates. RESULTS: The VE against COVID-19 hospitalisation (VEH) for the second booster dose compared to no vaccination was found to be 81.8% (95% confidence interval [95% CI]: 73.6-87.5) after 1 month post-vaccination. After 4 months, VEH was 72.2% (95% CI: 58.5-81.4), and after 6 months VEH was 49.0% (95% CI: 7.9-71.8). Similarly, VEH decreased after the first booster dose (1-month VEH=81.6% [95% CI: 75.6-86.1]; 2 months VEH=74.7% [95% CI: 68.2-79.9]; and 6 months VEH=57.4% [95% CI: 45.8-66.6]). VE against COVID-19 death (VED) was 92.9% (95% CI: 82.1-97.2) 2 months after the first booster vaccination, with VED being sustained until months 5 and 6 (VED=87.2%; 95% CI: 67.4-94.9). The VE after the second dose of the vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (VEI) (real-time polymerase chain reaction [RT-PCR]) was sustained at 5 months post-vaccination (40.6%; 95% CI: 25.6-52.5). CONCLUSION: We provide a comprehensive quantification of both VE and VE waning. These findings can guide policymakers to help evaluate the COVID-19 vaccination programme and minimise the effect of future COVID-19 in Aotearoa New Zealand.

Extruded plant protein two-dimensional scaffold structures support myoblast cell growth for potential applications in cultured meat.

Cultured meat has been proposed as a promising alternative to conventional meat products. Five different plant protein blends made from soy (from two different manufacturers), wheat, mung bean, and faba bean, were extruded to form low-moisture meat analogs (LMMA) and were used to assess LMMA scaffold potential for cultured meat application. Extruded LMMAs were characterized using scanning electron microscopy, water-holding capacity, total soluble matter, and mechanical properties. Two-dimensional LMMA scaffolds were seeded with C2C12 skeletal myoblast cells and cultured for 14 days, and cell attachment and morphology were evaluated. All five extrudates exhibited directionality of their fibrous protein structures but to varying degrees. Soy, wheat, mung bean, and faba bean-based LMMA scaffolds initially supported myoblast cell growth. However, after 14 days of culture, the extruded wheat LMMA exhibited superior myoblast cell growth. This may be attributed to the highly aligned fibrous structure of the extruded wheat LMMA as well as its elastic modulus, which closely approximated that of native skeletal muscle. Overall, two-dimensional structures of the extruded plant proteins support cell growth and advance the development of cultured meat.

Towards reliable data: Validation of a machine learning-based approach for microplastics analysis in marine organisms using Nile red staining.

Microplastic (MP) research faces challenges due to costly, time-consuming, and error-prone analysis techniques. Additionally, the variability in data quality across studies limits their comparability. This study addresses the critical need for reliable and cost-effective MP analysis methods through validation of a semi-automated workflow, where environmentally relevant MP were spiked into and recovered from marine fish gastrointestinal tracts (GITs) and blue mussel tissue, using Nile red staining and machine learning automated analysis of different polymers. Parameters validated include trueness, precision, uncertainty, limit of quantification, specificity, sensitivity, selectivity, and method robustness. For fish GITs a 95 ± 9 % recovery rate was achieved, and 87 ± 11 % for mussels. Polymer identification accuracies were 76 ± 8 % for fish GITs and 80 ± 13 % for mussels. Polyethylene terephthalate fragments showed more variability with lower accuracies. The proposed validation parameters offer a step towards quality management guidelines, as such aiding future researchers and fostering cross-study comparability.

Genitourinary Ultrasound.

Renal and genitourinary (GU) complaints are common reasons for presentation to the emergency department (ED). This article reviews the approach to renal, bladder, and testicular point-of-care ultrasound (POCUS) with specific discussions of commonly encountered ED pathology. It presents algorithms highlighting the clinical integration of renal and GU POCUS into the evaluation and management of these patients.

Takotsubo Syndrome or Peripartum Cardiomyopathy? Depends on Who You Are Talking to.

Takotsubo syndrome (otherwise known as broken-heart syndrome or left ventricular apical ballooning) is a rare cause of reversible heart failure that predominantly affects postmenopausal women. It was first described by Japanese researchers in the 1990s and has become established as a differential for heart failure following a physically or psychologically stressful event. This was popularised by a spike in cases following natural disasters in Japan. As the recognition of takotsubo syndrome in the differential diagnosis for sudden, onset heart failure in a previously healthy individual has grown, so has the discussion concerning takotsubo in the peripartum period. Peripartum cardiomyopathy is a rare cause of reversible heart failure in the latter weeks of pregnancy and the postpartum period. Morbidity and mortality for both cardiomyopathies can be highly variable, ranging from complete recovery of cardiac function to life threatening arrhythmias and even death. This rapid review highlights the similarities between both cardiomyopathies and challenges the hitherto assumption that both takotsubo and peripartum cardiomyopathies are distinct entities that can easily be distinguished from one another. The implications of this are significant within the context of the behavioural aspects of diagnosis, treatment, and outcome.

Microeukaryotes Associated with Freshwater Mussels in Rivers of the Southeastern United States.

Microeukaryotes are a diverse and often overlooked group of microbes that are important in food webs and other ecological linkages. Little is known about microeukaryotes associated with aquatic invertebrates, although filter feeders such as mussels are likely to take in and potentially retain microeukaryotes in their gut while feeding. Microeukaryotes such as apicomplexans have been reported in marine mussel species, but no studies have examined the presence of these microorganisms in freshwater mussels or how they relate to mussel host species or environmental conditions. In this study, microbial community DNA was extracted from the gut tissue of over 300 freshwater mussels, representing 22 species collected from rivers in the southeastern USA. Microeukaryote DNA was detected using PCR amplification, followed by the sequencing of positive amplicons. Microeukaryotes were found in 167 individual mussels (53%) of those tested. Amplicons included dinoflagellates/algae that differed between mussel species and are likely food sources that were distinct from those found in water and sediment samples analyzed concurrently. A total of 5% of the positive amplicons were non-photosynthetic alveolates that could represent parasitic microeukaryotes. Understanding the distribution of microeukaryotes in the freshwater mussel gut microbiome could further our understanding of the ongoing decline of mussel populations.

Health risks associated with the consumption of sea turtles: A review of chelonitoxism incidents and the presumed responsible phycotoxins.

Consuming the meat of some marine turtles can lead to a specific type of seafood poisoning known as chelonitoxism. A recent poisoning event (March 2024) on the Tanzanian island Pemba, resulting in the death of 9 people and hospitalization of 78 others, underscores the need to obtain an up to date overview and understanding of chelonitoxism. Here, we document a global overview of poisoning incidents resulting from the consumption of sea turtle flesh worldwide. All events combined involved over 2400 victims and 420 fatalities. Incidents were predominantly reported in remote regions (often islands) across the Indo-Pacific region. Reported health effects of consuming poisonous sea turtles include epigastric pain, diarrhea, vomiting, a burning mouth and throat sensation, and dehydration. In addition, ulcerative oeso-gastro-duodenal lesions, which occasionally have resulted in hospitalization and death, have been reported. Lyngbyatoxins have been suggested as (one of) the causative agents, originating from the cyanobacterium Moorena producens, growing epiphytically on the seagrass and seaweed consumed by green turtles. However, due to the limited evidence of their involvement, the actual etiology of chelonitoxism remains unresolved and other compounds may be responsible. The data outlined in this review offer valuable insights to both regulatory bodies and the general public regarding the potential risks linked to consuming sea turtles.

POCUS literature primer: key papers on cardiac and lung POCUS.

OBJECTIVE: Although point of care ultrasound (POCUS) use has become prevalent in medicine, clinicians may not be familiar with the evidence supporting its utility in patient care. The objective of this study is to identify the top five most influential papers published on the use of cardiac POCUS and lung POCUS in adult patients. METHODS: A 14-member expert panel from the Canadian Association of Emergency Physicians (CAEP) Emergency Ultrasound Committee and the Canadian Ultrasound Fellowship Collaborative used a modified Delphi process. Panel members are ultrasound fellowship trained or equivalent, are engaged in POCUS scholarship, and are leaders in POCUS locally and nationally in Canada. The modified Delphi process consisted of three rounds of sequential surveys and discussion to achieve consensus on the top five most influential papers on cardiac POCUS and lung POCUS. RESULTS: A total of 66 relevant papers on cardiac POCUS and 68 relevant papers on lung POCUS were nominated by the panel. There was 100% participation by the panel members in all three rounds of the modified Delphi process. At the end of this process, we identified the top five most influential papers on cardiac POCUS and lung POCUS. Papers include studies supporting the use of POCUS for accurately assessing left ventricular systolic function, diagnosing pericardial effusion, clarifying its test characteristics for pulmonary embolism, identifying pulmonary edema and pneumonia, as well as consensus statements on the use of cardiac and lung POCUS in clinical practice. CONCLUSION: We have created a list of the top five influential papers on cardiac POCUS and lung POCUS as an evidence-based resource for trainees, clinicians, and researchers. This will help trainees and clinicians better understand how to use POCUS when scanning the heart and lungs, and it will also help researchers better understand where to direct their scholarly efforts with future research.

RéSUMé: OBJECTIF: Bien que l'utilisation de l'échographie par point de soins (POCUS) soit devenue courante en médecine, les cliniciens ne sont peut-être pas familiarisés avec les données probantes qui appuient son utilité dans les soins aux patients. Cette étude a pour objectif d'identifier les cinq articles les plus influents publiés sur l'utilisation de la POCUS cardiaque et pulmonaire chez des patients adultes. MéTHODES: Un groupe d'experts composé de 14 membres du Comité des échographies d'urgence de l'Association canadienne des médecins d'urgence (ACEP) et du Canadian Ultrasound Fellowship Collaborative a utilisé un processus Delphi modifié. Les membres du comité sont des stagiaires en échographie ou l'équivalent, ils participent à des activités de recherche sur le POCUS et sont des chefs de file au niveau local et national au Canada. Le processus Delphi modifié consistait en trois rondes de sondages séquentiels et de discussions pour parvenir à un consensus sur les cinq articles les plus influents sur la POCUS cardiaque et la POCUS pulmonaire. RéSULTATS: Le panel a proposé un total de 66 articles pertinents sur la POCUS cardiaque et 68 documents pertinents sur la POCUS pulmonaire. Les membres du groupe ont participé à 100 % aux trois rondes du processus Delphi modifié. À la fin de ce processus, nous avons identifié les cinq principaux articles les plus influents sur le POCUS cardiaque et le POCUS pulmonaire. Les articles comprennent des études soutenant l'utilisation de POCUS pour évaluer avec précision la fonction systolique du ventricule gauche, diagnostiquer le épanchement péricardique, clarifier ses caractéristiques de test pour l'embolie pulmonaire, identifier l'œdème pulmonaire et la pneumonie, ainsi que des déclarations de consensus sur l'utilisation du POCUS cardiaque et pulmonaire dans la pratique clinique. CONCLUSION: Nous avons dressé une liste des cinq principaux articles influents sur le POCUS cardiaque et le POCUS pulmonaire en tant que ressource fondée sur des données probantes pour les stagiaires, les cliniciens et les chercheurs. Cela aidera les stagiaires et les cliniciens à mieux comprendre comment utiliser le POCUS pour scanner le cœur et les poumons, et cela aidera également les chercheurs à mieux comprendre où orienter leurs efforts scientifiques dans la recherche future.

Molecular mimicry in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection1,2, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

Discovery of SARS-CoV-2 papain-like protease (PLpro) inhibitors with efficacy in a murine infection model.

Vaccines and first-generation antiviral therapeutics have provided important protection against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PLpro) is one of the two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease have demonstrated clinical efficacy, known PLpro inhibitors have, to date, lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PLpro translates to in vivo efficacy in a preclinical setting. Here, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PLpro inhibitors, with lead compound PF-07957472 (4) providing robust efficacy in a mouse-adapted model of COVID-19 infection.

Experiences of families post treatment for childhood brain tumours during medical clinic consultations regarding health-related quality of life, unmet needs and communication barriers: A qualitative exploration.

BACKGROUND: Many studies highlight poor health-related quality of life (HRQoL) in children treated for brain tumours and their parents. However, little is known about the extent to which their informational, healthcare and communication needs regarding HRQoL are met during medical outpatient consultations. AIM: To explore the experiences of families regarding communication with physicians about HRQoL issues during consultations after treatment for childhood brain tumours. METHODS: Interviews were conducted with 18 families of children and adolescents aged 8-17 years after completion of brain tumour treatment. Participants had completed treatment within the last 5 years and were receiving regular outpatient follow-up care. Thematic analysis was undertaken using the Framework Method. RESULTS: Five main themes were identified: (i) unmet emotional and mental health needs; (ii) double protection; (iii) unmet information needs; (iv) communication barriers within consultations; and (v) finding a new normal. CONCLUSION: There was a need to improve communication between clinicians and these families, improve information provision, and overcome barriers to conversing with children within these outpatient consultations. Children and their parents should be supported to voice their current needs and concerns regarding their HRQoL. These findings will inform further development of the UK version of the 'KLIK' patient- and parent-reported outcome (PROM) portal.

Antimicrobial use in laboratory rodent facilities in Australia and New Zealand- a cross-sectional survey of veterinarians and facility managers.

This cross-sectional study surveyed veterinarians and facility managers to characterise the use of antimicrobials in laboratory rodent facilities within Australia and New Zealand. Most facilities (71%) reported routine administration of antimicrobials. The indications for antibiotic use reflected those described in publications and differed significantly to reasons for use in non-laboratory animals. Antimicrobials used include those of critical importance to human health, and access to these drugs is unregulated, as prescription-only classes are ordered through research catalogues, without human or veterinary physician prescriptions. The ways in which antimicrobials are used in Australian and New Zealand rodent facilities are likely contributing to antimicrobial resistance within rodent populations, particularly as they are largely administered in drinking water, risking subtherapeutic dosing. Much antimicrobial use reported is unnecessary and could be replaced with changes to husbandry and handling. The generation of resistance in both pathogenic and commensal microbes may also represent a work health and safety issue for humans working with these animals. Reported disposal of antimicrobials included discharge into wastewater, without inactivation, and some respondents reported disposal of substrate, or soiled bedding, nesting material, and disposable enrichment items, from treated animals and medicated feed into landfill, without prior inactivation. Environmental contamination with resistant microbes and antimicrobials is a significant driver of antimicrobial resistance. As such, significant opportunities exist to implement judicious and responsible use of antimicrobials within research rodent facilities in Australia and New Zealand, with a particular focus on instituting aseptic surgery, optimising dosing regimens, and inactivation of medicated water and substrate before disposal.

Cross-country assessment of the unique contributions of psychological factors to vaccination: Perspectives on the COVID-19 pandemic.

We have identified the most relevant and significant psychological factors in relation to COVID-19 vaccination attitudes in Ghana, Germany, New Zealand and India. This study recruited 1822 participants from the general populations of India (n = 411), New Zealand (n = 413), Ghana (n = 523) and Germany (n = 475) to participate in a cross-sectional online survey. After controlling for the country of residence, individual psychological factors played a significant role in shaping attitudes towards COVID-19 vaccination. The results also revealed strong direct predictors that explained significant portions of the variance in the COVID-19 vaccination attitudes. Positive affect emerged as the strongest contributor in Ghana (7%), while self-compassion strongly influenced COVID-19 vaccination attitudes in India (66%). Dispositional optimism was the strongest predictor in New Zealand (5%). In Germany, compassion towards others was the strongest positive predictor (2%), while psychological distress had a strong negative impact (3%). Results highlight the importance of promoting emotional well-being to enhance vaccination coverage.

Novel approach for tracheal resection in Morquio a syndrome with end-stage critical airway obstruction: a UK case series.

BACKGROUND: Mucopolysaccharidosis (MPS) type IVA is a rare lysosomal storage disorder caused by aberrations of the N-acetyl-galactosamine-6-sulfatase (GALNS) enzyme. MPS IVA is associated with a wide gamut of respiratory and airway disorders that manifest in a continuum of severity. In individuals exhibiting severe phenotypic expression, terminal stages of the disease frequently culminate in life-threatening, critical airway obstruction. These manifestations of end-stage disease are engendered by an insidious progression of multi-level airway pathologies, comprising of tracheomalacia, stenosis, tortuosity and 'buckling'. Historically, the management of end-stage airway disease has predominantly leaned towards palliative modalities. However, contemporary literature has posited that the potential benefits of tracheal resection with aortopexy, performed under cardiopulmonary bypass (CPB), may offer a promising therapeutic option. In this context, we report on outcomes from patients undergoing a novel approach to tracheal resection that is combined with manubrial resection, leading to improved airway calibre, obviating the requisition for CPB. RESULTS: In this study, seven patients with severe MPS IVA exhibited clinical symptoms and radiological evidence indicative of advanced airway obstruction. All patients had a tracheal resection with a partial upper manubriectomy via transcervical approach, which did not require CPB. The surgical cohort consisted of 5 females and 2 males, the median age was 16 years (range 11-19) and the median height was 105.6cm (range 96.4-113.4). Postoperatively, significant improvements were seen in forced expiratory volume in 1 second (FEV1), with a mean increase of 0.68 litres (95% CI: 0.45-0.91; SD: 0.20). Notably, other spirometry variables also showed meaningful improvements, providing evidence of positive treatment effects. Furthermore, there were no major long-term complications, and the procedure resulted in a significant enhancement in patient-reported domains using PedsQL (version 4.0). CONCLUSIONS: This study represents the largest case series to date, on tracheal resection in patients with severe MPS IVA. Our findings demonstrate the effectiveness of the transcervical approach with partial manubriectomy for improving respiratory function and quality of life for individuals with advanced airway obstruction. Tracheal resection presents a promising treatment modality for severe cases of MPS IVA. Successful outcomes rely on meticulous multidisciplinary assessment, judicious decision-making, and appropriate timing of tracheal surgery. Further research and long-term follow-up studies are warranted to validate the long-term efficacy and safety of this approach.

A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

Examining the neurostructural architecture of intelligence: The Lothian Birth Cohort 1936 study.

Examining underlying neurostructural correlates of specific cognitive abilities is practically and theoretically complicated by the existence of the positive manifold (all cognitive tests positively correlate): if a brain structure is associated with a cognitive task, how much of this is uniquely related to the cognitive domain, and how much is due to covariance with all other tests across domains (captured by general cognitive functioning, also known as general intelligence, or 'g')? We quantitatively address this question by examining associations between brain structural and diffusion MRI measures (global tissue volumes, white matter hyperintensities, global white matter diffusion fractional anisotropy and mean diffusivity, and FreeSurfer processed vertex-wise cortical volumes, smoothed at 20mm fwhm) with g and cognitive domains (processing speed, crystallised ability, memory, visuospatial ability). The cognitive domains were modelled using confirmatory factor analysis to derive both hierarchical and bifactor solutions using 13 cognitive tests in 697 participants from the Lothian Birth Cohort 1936 study (mean age 72.5 years; SD = .7). Associations between the extracted cognitive factor scores for each domain and g were computed for each brain measure covarying for age, sex and intracranial volume, and corrected for false discovery rate. There were a range of significant associations between cognitive domains and global MRI brain structural measures (r range .008 to .269, p < .05). Regions implicated by vertex-wise regional cortical volume included a widespread number of medial and lateral areas of the frontal, temporal and parietal lobes. However, at both global and regional level, much of the domain-MRI associations were shared (statistically accounted for by g). Removing g-related variance from cognitive domains attenuated association magnitudes with global brain MRI measures by 27.9-59.7% (M = 46.2%), with only processing speed retaining all significant associations. At the regional cortical level, g appeared to account for the majority (range 22.1-88.4%; M = 52.8% across cognitive domains) of regional domain-specific associations. Crystallised and memory domains had almost no unique cortical correlates, whereas processing speed and visuospatial ability retained limited cortical volumetric associations. The greatest spatial overlaps across cognitive domains (as denoted by g) were present in the medial and lateral temporal, lateral parietal and lateral frontal areas.