Mepolizumab in children and adolescents with severe eosinophilic asthma not eligible for omalizumab: a single Center experience.

BACKGROUND: Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. AIM: To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV1), mid expiratory flow (FEF25-75%), and blood eosinophil count. METHODS: Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab. RESULTS: Sixteen participants (age 7-17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients' daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 109/L, p < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p = 0.10), ACT scores (mean Δ2.88 ± 6.71, p = 0.17), FEV1 z-scores (mean Δ-0.99 ± 1.88, p = 0.053), FEF25-75% z-scores (mean Δ-0.65 ± 1.61, p = 0.13), FeNO (mean Δ-20.09 ± 80.86, p = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p = 0.09). CONCLUSION: Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage.

Cognitive profile of people with mild behavioral impairment in Brain Health Registry participants.

OBJECTIVES: Dementia assessment includes cognitive and behavioral testing with informant verification. Conventional testing is resource-intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. The aim of this study was to assess the relationship between informant-rated behavioral changes and participant-completed neuropsychological test performance in older adults, both measured remotely via an online unsupervised platform, the Brain Health Registry (BHR). DESIGN: Observational cohort study. SETTING: Community-dwelling older adults participating in the online BHR. Informant reports were obtained using the BHR Study Partner Portal. PARTICIPANTS: The final sample included 499 participant-informant dyads. MEASUREMENTS: Participants completed online unsupervised neuropsychological assessment including Forward Memory Span, Reverse Memory Span, Trail Making B, and Go/No-Go tests. Informants completed the Mild Behavioral Impairment Checklist (MBI-C) via the BHR Study Partner portal. Cognitive performance was evaluated in MBI+/- individuals, as was the association between cognitive scores and MBI symptom severity. RESULTS: Mean age of the 499 participants was 67, of which 308/499 were females (61%). MBI + status was associated with significantly lower memory and executive function test scores, measured using Forward and Reverse Memory Span, Trail Making Errors and Trail Making Speed. Further, significant associations were found between poorer objectively measured cognitive performance, in the domains of memory and executive function, and MBI symptom severity. CONCLUSION: These findings support the feasibility of remote, informant-reported behavioral assessment utilizing the MBI-C, supporting its validity by demonstrating a relationship to online unsupervised neuropsychological test performance, using a previously validated platform capable of assessing early dementia risk markers.

Modelling the Arctic wave-affected marginal ice zone: a comparison with ICESat-2 observations.

We evaluate marginal ice zone (MIZ) extent in a wave-ice 25 km-resolution coupled model, compared with pan-Arctic wave-affected sea-ice regions derived from ICESat-2 altimetry over the period December 2018-May 2020. By using a definition of the MIZ based on the monthly maximum of the wave height, we suggest metrics to evaluate the model taking into account the sparse coverage of ICESat-2. The model produces MIZ extents comparable to observations, especially in winter. A sensitivity study highlights the need for strong wave attenuation in thick, compact ice but weaker attenuation as sea ice forms, as the model underestimates the MIZ extent in autumn. This underestimation may be due to limited wave growth in partially covered ice, overestimated sea-ice concentration or the absence of other processes affecting floe size. We discuss our results in the context of other definitions of the MIZ based on floe size and sea-ice concentration, as well as the potential impact of wave-induced fragmentation on ice dynamics, found to be minor at the climate scales investigated here. This article is part of the theme issue 'Theory, modelling and observations of marginal ice zone dynamics: multidisciplinary perspectives and outlooks'.

Varying aerobic capacity in relation to breeding stage and reproductive success in giant petrels (Macronectes spp.).

Reproduction, and parental care in particular, are among the most energy-demanding activities within the annual cycle of adult birds. Parents that cannot meet the metabolic demands and other physiological costs of raising offspring may opt to abandon chicks in favour of self-maintenance and future reproduction. Recent work examining reproductive trade-offs in birds revealed an important role of oxygen carrying capacity in mediating variation in parental effort. This study explores the aerobic factors underlying the success or failure of parental care in two closely-related petrel species during their breeding season on Bird Island, South Georgia: northern giant petrels (Macronectes halli) and southern giant petrels (M. giganteus). Failed breeders of both sexes and species had significantly lower hematocrit levels (by 5.48 ± 0.64%) than successful breeders, and reticulocyte counts also tended to be lower in failed males, consistent with the hypothesis that parental care and workload depend on aerobic capacity. We discuss these results in relation to differences in the foraging ecology of both species and sexes.

Epidemiological Survey on Gastrointestinal and Pulmonary Parasites in Cats Around Toulouse (France).

Various feline parasites are potentially zoonotic thus establishing factors associated with parasitism is of animal and public health interest. The aim of this study was to determine the prevalence of endoparasites in client-owned cats, living in the area of Toulouse, France, over the period 2015 - 2017, and to investigate possible risk factors. A total of 498 faecal samples from cats of the University Animal Hospital of Ecole Nationale Vétérinaire de Toulouse were analysed, 448 from cats presented for consultation and 50 at post-mortem. Analysis was performed using a commercial flotation enrichment method with a hypersaturated sodium chloride solution and Baermann technique. Further examination of the gastrointestinal tract contents was conducted on necropsied cats. Overall, 11.6 % of cats were positive for endoparasites; 50 (11.2 %) consultation cases and 8 (16 %) post-mortem cases, with no significant difference in prevalence between the groups. Amongst infected cats, most were infected by a single species of parasite and 10.3 % (n=6) were infected with two or more. The most common parasite was Toxocara cati with a prevalence of 9.4 % (n=47). Other endoparasites encountered were: Cystoisospora sp 1.0 % (n=5), Aelurostrongylus abstrusus 1.0 % (n=5), Strongyloides sp 0.6 % (n=3), Dipylidium caninum 0.4 % (n=2), Aonchotheca putorii 0.2 % (n=1), Ancylostomatidae 0.2 % (n=1) and Toxascaris leonina 0.2 % (n=1). The examination of the gastronintestinal tract contents of the necropsied cats revealed Mesocestoides sp 0.4 % (n=2) and Tænia (Hydatigera) tæniaeformis sensu lato 0.2 % (n=1) which are seldomly diagnosed by flotation methods. In this study, increasing age and neutered status were statistically associated with reduced odds of infection by endoparasites (helminth and coccidian). Predictors of significantly increased risk included being male, intact, and not receiving regular anthelmintic treatment. The same risk factors were highlighted specifically for Toxocara cati infections, with rural location being an additional risk factor for infection.

Pre-procedural pacing bias among transcatheter aortic valves with higher post-procedure pacing rates: evidence from the UK TAVI Registry.

Rates of permanent pacemaker (PPM) implantation following transcatheter aortic valve implantation (TAVI) are higher than following surgery and are dependent on patient factors and valve type. There is an increasing trend towards pre-emptive PPM insertion in patients with significant conduction disease prior to TAVI. We report results from the British Cardiovascular Intervention Society (BCIS) on pre- and post-procedural PPM implantation in the TAVI population. All centres in the United Kingdom performing TAVI are required to submit data on all TAVI procedures to the National database which are then reported annually. During 2015, there were 2373 TAVI procedures in the UK. 22.4% of TAVI patients had a PPM implanted either pre-procedure (including the distant past), or during the in-hospital procedural episode. Of these, 7.9% were pre-procedure and 14.5% post-procedure. Overall PPM rates were Edwards Sapien (13.5%), Medtronic CoreValve (28.2%) and Boston Lotus (42.1%; p < 0.01). Pre-procedure pacing rates were Edwards Sapien (6.0%), Medtronic CoreValve (9.1%) and Boston Lotus (12.3%; p < 0.01). Pre-procedural pacing rates for the Boston Lotus valve have risen year-on-year from 5.8% (2013) to 8.6% (2014) to 12.3% (2015). The UK TAVI Registry demonstrates a pre-procedural permanent pacing bias amongst patients receiving transcatheter valves with higher post-procedure pacing rates. Pre-emptive permanent pacing is likely to be responsible for this difference.

Review of petroleum toxicity and identifying common endpoints for future research on diluted bitumen toxicity in marine mammals.

Large volumes of conventional crude oil continue to be shipped by sea from production to consumption areas across the globe. In addition, unconventional petroleum products also transverse pelagic habitats; for example, diluted bitumen from Canada's oilsands which is shipped along the Pacific coast to the United States and Asia. Therefore, there is a continuing need to assess the toxicological consequences of chronic and catastrophic petroleum spillage on marine wildlife. Peer-reviewed literature on the toxicity of unconventional petroleum such as diluted bitumen exists for teleost fish, but not for fauna such as marine mammals. In order to inform research needs for unconventional petroleum toxicity we conducted a comprehensive literature review of conventional petroleum toxicity on marine mammals. The common endpoints observed in conventional crude oil exposures and oil spills include hematological injury, modulation of immune function and organ weight, genotoxicity, eye irritation, neurotoxicity, lung disease, adrenal dysfunction, metabolic and clinical abnormalities related to oiling of the pelage, behavioural impacts, decreased reproductive success, mortality, and population-level declines. Based on our findings and the body of literature we accessed, our recommendations for future research include: 1) improved baseline data on PAH and metals exposure in marine mammals, 2) improved pre- and post-spill data on marine mammal populations, 3) the use of surrogate mammalian models for petroleum toxicity testing, and 4) the need for empirical data on the toxicity of unconventional petroleum to marine mammals.

Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution.

BACKGROUND: Trypanosomes are single-celled eukaryotic parasites characterised by the unique biology of their mitochondrial DNA. African livestock trypanosomes impose a major burden on agriculture across sub-Saharan Africa, but are poorly understood compared to those that cause sleeping sickness and Chagas disease in humans. Here we explore the potential of the maxicircle, a component of trypanosome mitochondrial DNA to study the evolutionary history of trypanosomes. RESULTS: We used long-read sequencing to completely assemble maxicircle mitochondrial DNA from four previously uncharacterized African trypanosomes, and leveraged these assemblies to scaffold and assemble a further 103 trypanosome maxicircle gene coding regions from published short-read data. While synteny was largely conserved, there were repeated, independent losses of Complex I genes. Comparison of pre-edited and non-edited genes revealed the impact of RNA editing on nucleotide composition, with non-edited genes approaching the limits of GC loss. African tsetse-transmitted trypanosomes showed high levels of RNA editing compared to other trypanosomes. The gene coding regions of maxicircle mitochondrial DNAs were used to construct time-resolved phylogenetic trees, revealing deep divergence events among isolates of the pathogens Trypanosoma brucei and T. congolense. CONCLUSIONS: Our data represents a new resource for experimental and evolutionary analyses of trypanosome phylogeny, molecular evolution and function. Molecular clock analyses yielded a timescale for trypanosome evolution congruent with major biogeographical events in Africa and revealed the recent emergence of Trypanosoma brucei gambiense and T. equiperdum, major human and animal pathogens.

Surgery with and without adjuvant radiotherapy is associated with similar survival in T4 colon cancer.

AIM: There is little evidence regarding the role of adjuvant radiotherapy for colon cancer. Despite this, national consensus guidelines recommend consideration of radiation for patients with T4 colon cancer. Large comparative studies may be beneficial in clarifying the potential benefit of postoperative radiation for this cohort. METHOD: We compared the overall survival between patients treated with surgery with and without adjuvant radiation using the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results Program (SEER), as well as disease-specific survival using SEER. Cox proportional hazards models and propensity score matching were used to adjust for relevant confounders. RESULTS: There were a total of 18 776 patients in the NCDB cohort and 9926 patients in the SEER cohort. After propensity score matching, there was no statistically significant difference in overall mortality between surgery with and without radiation in the NCDB [hazard ratio (HR) 1.11; 95% CI 0.93-1.31; P = 0.25] or in SEER (HR 1.20; 95% CI 0.84-1.72; P = 0.32). Additionally, using SEER, we found no statistically significant difference in disease-specific mortality between these two groups (HR 1.13; 95% CI 0.76-1.67; P = 0.54). CONCLUSION: Using the NCDB and SEER, we found no statistically significant difference in overall survival or disease-specific survival between patients treated with and without adjuvant radiation. Further studies should evaluate the impact of adjuvant radiotherapy on local control and prevention of recurrence-related morbidity in patients with T4 colon cancer.

The construct validity of general and specific dimensions of personality pathology.

BACKGROUND: Modern personality disorder (PD) theory and research attempt to distinguish transdiagnostic impairments common to all PDs from constructs that explain varied PD expression. Bifactor modeling tests such distinctions; however, the only published PD criteria bifactor analysis focused on only 6 PDs and did not examine the model's construct validity. METHODS: We examined the structure and construct validity of competing PD criteria models using confirmatory and exploratory factor analytic methods in 628 patients who completed structured diagnostic interviews and self-reports of personality traits and impairment. RESULTS: Relative to alternative models, two bifactor models - one confirmatory model with 10 specific factors for each PD (acceptable fit) and one exploratory model with four specific factors resembling broad personality domains (excellent fit) - fit best and were compared via connections with external criteria. General and specific factors related meaningfully and differentially to personality traits, internalizing symptoms, substance use, and multiple indices of psychosocial impairment. As hypothesized, the general factor predicted interpersonal dysfunction above and beyond other psychopathology. The general factor also correlated strongly with many pathological personality traits. CONCLUSIONS: The present study supported the validity of a model with both a general PD impairment dimension and separate individual difference dimensions; however, it also indicated that currently prominent models, which assume general PD impairments and personality traits are non-overlapping, may be misspecified.

Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis.

OBJECTIVES: Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS. METHODS: Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life. RESULTS: A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life. CONCLUSIONS: The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.

Long-Term Functional Outcomes in Military Service Members and Veterans After Traumatic Brain Injury/Polytrauma Inpatient Rehabilitation.

OBJECTIVE: To determine the effect of the established polytrauma/traumatic brain injury (TBI) infrastructure on immediate posttreatment functional gains, the long-term sustainability of any gains, and participation-related community reintegration outcomes in a baseline cohort of patients 8 years postadmission. DESIGN: Retrospective review and prospective repeated measures of an inception cohort. SETTING: Polytrauma rehabilitation center (PRC). PARTICIPANTS: Patients consecutively admitted to the PRC inpatient rehabilitation unit during its first full fiscal year, 2006 (N=44). INTERVENTIONS: The PRC infrastructure and formalized rehabilitation for polytrauma/TBI. MAIN OUTCOME MEASURES: FIM scores at admission, discharge, 3 months, and 8 years postdischarge; participation-related socioeconomic factors reflecting community reintegration 8 years after admission. RESULTS: Functional gains were statistically significantly increased from admission to discharge. Improvements were maintained at both 3 months postdischarge and 8 years postdischarge. The socioeconomic data collected at 8-year follow-up showed >50% either competitively employed or continuing their education and 100% living in a noninstitutionalized setting. CONCLUSIONS: This study addresses a concern regarding the long-term functional outcomes of rehabilitation patients treated by the established infrastructure of the Polytrauma System of Care inpatient rehabilitation centers. The results suggest that polytrauma/TBI rehabilitation care using a comprehensive, integrated approach is effective and durable in achieving functional gains and successful community reintegration within our initial PRC cohort. Follow-up of subsequent fiscal year cohorts would add to the validity of these outcome findings.

Does anyone else look familiar? Influencing identification decisions by asking witnesses to re-examine the lineup.

Two experiments were conducted to see if asking witnesses to take another look at the lineup after they voiced their identification decisions would alter their choices, and if confirming feedback could then be used to solidify the selections they shifted to. Participants watched a simulated crime and were asked to identify the culprit from a photographic lineup. After voicing their identification decisions, participants were prompted to re-examine the lineup. Half of the participants then received confirming feedback for their decisions, regardless of whether they shifted to a new picture or not. Later on, a different experimenter escorted participants to a second room and administered the same lineup again. In Experiment 1 (N = 432), biased instructions were used to encourage choosing, and when participants were prompted to re-examine the lineup, 70% changed their identification decisions and selected a different picture. When that new selection was reinforced with feedback and participants were given a second opportunity to identify the culprit at a later time, 72% selected the picture they shifted to as the culprit. Participants who made their decisions more quickly were less likely to shift, but accuracy did not predict shifting. This general pattern of findings was replicated using unbiased instructions in Experiment 2 (N = 237). Results suggest that prompting witnesses to re-examine the lineup can often lead witnesses to change their identification decisions, and when the altered choice is reinforced, they will often stay with that influenced decision over time, asserting it with a high degree of confidence. (PsycINFO Database Record

Effects of fat supplementation on plasma glucose, insulin and fatty acid analysis in ponies maintained on a forage-based diet.

The objective of this study was to observe how fat incorporated into an equine forage-based diet through supplementation altered levels of plasma glucose, insulin and fatty acids. Five Shetland/Hackney cross pony mares were fed alfalfa pellet diets top dressed with commercially available vegetable oil (blend of soya bean, canola and corn oils) at 0%, 5%, 10% or 15% of diet. Ponies were randomly assigned one of four diets to start, with a 14-day adjustment period between transitioning to another one of the four diets. Ponies were gradually adapted to the new diet within the 14-day period before a five-day trial period. Each pony received all four diets by the end of the study. Each trial was a five-day period with a three-day sample collection. Blood samples for each collection week were taken 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270 min and at 5, 6, 7, 8, 9 and 10 hr post-feeding. Excess fat did not impact plasma glucose (p > .1), nor did it affect blood plasma insulin concentration. While there was no time alteration found for plasma fatty acid concentration (p > .1), C14:0 increased when ponies were fed 0% fat and C18:2 decreased when ponies were fed 0% fat. Plasma fatty acids (% of total FA) were higher in C18:0, C18:1, C18:2 and C20:1 in the added fat diets (p < .1). These findings suggest the amounts reported in this study of fat supplementation on a forage-based diet did influence the fatty acid analysis within the pony, but did not negatively impact blood glucose and insulin concentrations.

The current standard of Foot and Ankle Fellowship in the UK.

BACKGROUND: The aim of this study was to evaluate the current standards of Fellowship training in Foot and Ankle Surgery Fellowship in the UK. METHODS: Thirteen UK post-FRCS (Tr&Orth) or equivalent Fellows completed a questionnaire detailing their outpatient, surgical, teaching and research experience, along with documenting their supervision and terms of employment. RESULTS: A Fellow attended a mean of 2.5 (0.5-4) clinics and 3.84 (2-7) theatre sessions per week. 62% of Fellows had independent clinics. The three largest sub-specialty areas experienced were forefoot surgery, mid or/hindfoot arthritis and deformity correction. 82% of Fellows had a regular MDT meeting. All were involved in both teaching and research, but only 64% had timetabled research sessions. All Fellows were satisfied with their experience and would recommended the Fellowship. CONCLUSIONS: The current standard of a post FRCS (Tr&Orth) Fellowship in Foot & Ankle surgery in the UK has been defined. Further improvement will require all Fellows to be involved in a regular MDT meetings, work in an independent clinic, have guaranteed timetabled research time and a ring fenced study leave budget.

Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial.

BACKGROUND: Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. METHOD: We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups. RESULTS: The most statistically significant and clinically recognizable model comprised five subgroups. The largest, 'core' subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms - a group which combined features of both of the above (14%). The smallest 'avoidant-inactive' subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups. CONCLUSIONS: In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

Measures of and changes in heart rate variability in pediatric heart transplant recipients.

Heart rate variability is primarily regulated by the autonomic nervous system. Heart transplant recipients undergo surgical denervation of the graft, which results in interruption of autonomic innervation with resultant diminished heart rate variability although some degree of autonomic control may return. This study aimed to characterize heart rate variability in this population. We report a retrospective review of Holter monitor data from transplanted patients between 2005 and 2013. Studies with significant atrial or ventricular arrhythmias were excluded. We evaluated changes over time and compared standard time domain measures to published pediatric normal values. Data were reviewed from 582 monitors in 152 patients. We found that pediatric heart transplant recipients have lower heart rate variability than age-matched controls and higher average heart rate in recipients older than 3 years. There is an increase in measures of variability through the first 3 years post-transplant with plateau after that time. Surgical technique in regard to interruption of the vagus nerve does not affect variability, nor does underlying congenital vs acquired heart disease.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) in children: a randomized controlled trial.

BACKGROUND: Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) was introduced to adult anaesthesia to improve the safety of airway management during apnoea before intubation. The objective of our study was to determine whether THRIVE safely prolongs apnoeic oxygenation in children. METHODS: This was a randomized controlled trial in 48 healthy children, with normal airways and cardiorespiratory function, in age groups 0-6 and 7-24 months, 2-5 and 6-10 yr old, presenting for elective surgery or imaging under general anaesthesia. All children were induced with sevoflurane, O2, and N2O, followed by muscle relaxation with rocuronium, and standardized preoxygenation with bag-and-mask ventilation. The control arm received jaw support during apnoea, whereas the THRIVE arm received jaw support during apnoea and age-specific flow rates. The primary outcome was to demonstrate that children allocated to THRIVE maintain transcutaneous haemoglobin saturation at least twice as long as the expected age-dependent apnoea time in the control group. RESULTS: Both study arms (each n=24) were similar in age and weight. The apnoea time was significantly shorter in the control arm: average 109.2 (95% CI 28.8) s in the control arm and 192 s in the THRIVE arm (0-6 months), 147.3 (95% CI 18.9) and 237 s (7-24 months), 190.5 (95% CI 15.3) and 320 s (2-5 yr), and 260.8 (95% CI 37.5) and 430 s (6-10 yr), respectively. Average transcutaneous haemoglobin saturation remained at 99.6% (95% CI 0.2) during THRIVE. Transcutaneous CO2 increased to a similar extent in both arms, with 2.4 (95% CI 0.5) mm Hg min-1 for the control arm and 2.4 (95% CI 0.4) mm Hg min-1 for the THRIVE arm. CONCLUSION: Transnasal humidified rapid-insufflation ventilatory exchange prolongs the safe apnoea time in healthy children but has no effect to improve CO2 clearance. CLINICAL TRIAL REGISTRATION: ACTRN12615001319561.

S-shaped non-paraxial corrections to general astigmatic beams.

Non-paraxial perturbation wave equations are solved for general astigmatic Gaussian beams for the first time, to the best of our knowledge, in the angular spectrum representation by taking into account generic boundary conditions. Expressions for second-order corrections are derived and exemplified with an optical cavity made of two cylindrical mirrors. Non-paraxial corrections can lead, depending on the choice of boundary conditions, to a transverse S-shaped beam mode, which has been qualitatively been observed in a highly divergent non-planar four-mirror cavity.

T Lymphocytes in Histiocytic Sarcomas of Flat-Coated Retriever Dogs.

Flat-Coated Retriever dogs are predisposed to the development of histiocytic sarcoma (HS), a poorly differentiated, highly malignant neoplasm. The authors have previously documented a significant lymphocytic infiltrate in such tumors. The objective of this study was to examine the presence and expression of regulatory T cells in HS tumor samples. Forty tumors were included in this study. All tumors were immunolabeled for CD3, CD79a, CD25, CD45RA, and FOXP3. The proportion of positive cells was compared between tumors presenting as a localized primary soft tissue mass (soft tissue origin HS) and disseminated HS affecting viscera, especially the spleen (splenic origin HS). By immunohistochemistry, 95% of infiltrating T cells were positive for Foxp3 in all sections, suggesting the presence of regulatory T cells. The proportion of cells positive for FOXP3 was higher in the tumors arising in soft tissues, whereas the proportion of CD45RA-positive cells was higher in the splenic origin HS. Canine HS has an aggressive clinical behavior and is uniformly fatal. The difference in the proportion of tumor-infiltrating lymphocytes positive for these 2 markers in the 2 locations may represent differences in tumor microenvironment between the 2 sites.