Identification of premature infant states in relation to introducing oral feeding

Background Recognizing oral readiness signs in infants is vital when planning the introduction of oral feeding. However, with premature infants, this can be difficult to gauge accurately because of immature development. Methods Twenty three staff from a level 2 neonatal unit participated. A questionnaire elicited knowledge about oral readiness and other factors related to oral feeding with premature infants. Participant knowledge of the written Als (1986) infant state descriptors was completed. A comparison was made of the skills in identification of the various infant states on video without and with written descriptors (Als, 1986). Correlations investigated if years of experience and grade had any relation to accurate infant state identification. Results There was wide variation in the type of training about premature infant feeding participants had received. Participants (65%) recognized the importance of oral readiness signs in relation to feeding development. A Wilcoxon signed ranks test revealed no significant differences in ability to identify infant states without and with the written Als (1986) descriptors when observing infant video materials. When not using the written descriptors, there was a strong negative correlation between grade and the identification of the [Active sleep] state, (p < 0.01), and a strong positive correlation between grade and the identification of the [Drowsy] state, (p < 0.05). There were no strong correlations between grade and years working when using the written descriptors. Conclusion Oral readiness signs are important when introducing oral feeding with premature infants. However, accurate identification of oral readiness remains challenging

A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol

Background: Sequential B cell-targeted immunotherapy with BAFF antagonism (belimumab) and B cell depletion (rituximab) may enhance B cell targeting in ANCA-associated vasculitis (AAV) through several mechanisms. Methods: Study design: COMBIVAS is a randomised, double-blind, placebo-controlled trial designed to assess the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3 AAV. The recruitment target is 30 patients who meet the criteria for inclusion in the per-protocol analysis. Thirty-six participants have been randomised to one of the two treatment groups in a 1:1 ratio: either rituximab plus belimumab or rituximab plus placebo (both groups with the same tapering corticosteroid regimen), and recruitment is now closed (final patient enrolled April 2021). For each patient, the trial will last for 2 years comprising a 12-month treatment period followed by a 12-month follow-up period. Participants: Participants have been recruited from five of seven UK trial sites. Eligibility criteria were age ≥ 18 years and a diagnosis of AAV with active disease (newly diagnosed or relapsing disease), along with a concurrent positive test for PR3 ANCA by ELISA. Interventions: Rituximab 1000 mg was administered by intravenous infusions on day 8 and day 22. Weekly subcutaneous injections of 200 mg belimumab or placebo were initiated a week before rituximab on day 1 and then weekly through to week 51. All participants received a relatively low prednisolone (20 mg/day) starting dose from day 1 followed by a protocol-specified corticosteroid taper aiming for complete cessation by 3 months. Outcomes: The primary endpoint of this study is time to PR3 ANCA negativity. Key secondary outcomes include change from baseline in naïve, transitional, memory, plasmablast B cell subsets (by flow cytometry) in the blood at months 3, 12, 18 and 24; time to clinical remission; time to relapse; and incidence of serious adverse events. Exploratory biomarker assessments include assessment of B cell receptor clonality, B cell and T cell functional assays, whole blood transcriptomic analysis and urinary lymphocyte and proteomic analysis. Inguinal lymph node and nasal mucosal biopsies have been performed on a subgroup of patients at baseline and month 3. Discussion: This experimental medicine study provides a unique opportunity to gain detailed insights into the immunological mechanisms of belimumab-rituximab sequential therapy across multiple body compartments in the setting of AAV. Trial registration: ClinicalTrials.gov NCT03967925. Registered on May 30, 2019

Exponential Kleisli monoids as Eilenberg-Moore algebras

Lax monoidal powerset-enriched monads yield a monoidal structure on the category of monoids in the Kleisli category of a monad. Exponentiable objects in this category are identified as those Kleisli monoids with algebraic structure. This result generalizes the classical identification of exponentiable topological spaces as those whose lattice of open subsets forms a continuous lattice.Comment: v2: minor typos correcte

Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial.

BACKGROUND: Rituximab is effective as therapy for induction of remission in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the effect of rituximab is not sustained, and subsequent relapse rates are high, especially in patients with a history of relapse. There is a need to identify whether maintenance therapy with rituximab is superior to the current standard of azathioprine or methotrexate for prevention of relapse following induction with rituximab. METHODS/DESIGN: RITAZAREM is an international, multicenter, open-label, randomized controlled trial designed to demonstrate the superiority of repeated doses of intravenous rituximab compared to daily orally administered azathioprine as a relapse prevention strategy in patients with AAV with relapsing disease who undergo induction of remission with rituximab. Patients with AAV will be recruited at the time of relapse and will receive rituximab and glucocorticoid induction therapy. If the disease is controlled by 4 months, patients will be randomized in a 1:1 ratio to receive rituximab (1000 mg every 4 months for five doses) or azathioprine (2 mg/kg/day) as maintenance therapy. Patients will be followed for a minimum of 36 months. The primary outcome is the time to disease relapse. It is estimated that 190 patients will need to be recruited to ensure that at least 160 are randomized. DISCUSSION: The RITAZAREM trial will provide the largest trial dataset for the use of rituximab as remission-induction therapy for patients with AAV comparing two remission-maintenance strategies following induction with rituximab, and explore whether prolonged B-cell depletion leads to sustained treatment-free remissions after discontinuation of immunosuppressive therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01697267 . Registered on 31 August 2012

A novel modelling approach to energy transport in a respiratory system

In this paper, energy transport in a respiratory tract is modelled using the finite element method for the first time. The upper and lower respiratory tracts are approximated as a one-dimensional domain with varying cross sectional and surface areas and the radial heat conduction in the tissue is approximated using the one dimensional cylindrical coordinate system. The governing equations are solved using one-dimensional linear finite elements with convective and evaporative boundary conditions on the wall. The results obtained for the exhalation temperature of the respiratory system have been compared with the available animal experiments. The study of a full breathing cycle indicates that evaporation is the main mode of heat transfer and convection plays almost negligible role in the energy transport. This is inline with the results obtained from animal experiments

Long-term airborne measurements of pollutants over the United Kingdom to support air quality model development and evaluation

The ability of regional air quality models to skilfully represent pollutant distributions throughout the atmospheric column is important to enabling their skilful prediction at the surface. This provides a requirement for model evaluation at elevated altitudes, though observation datasets available for this purpose are limited. This is particularly true of those offering sampling over extended time periods. To address this requirement and support evaluation of regional air quality models such as the UK Met Offices Air Quality in the Unified Model (AQUM), a long-term, quality-assured dataset of the three-dimensional distribution of key pollutants was collected over the southern United Kingdom from July 2019 to April 2022. Measurements were collected using the Met Office Atmospheric Survey Aircraft (MOASA), a Cessna 421 instrumented for this project to measure gaseous nitrogen dioxide, ozone, sulfur dioxide and fine-mode (PM2.5) aerosol. This paper introduces the MOASA measurement platform, flight strategies and instrumentation and is not intended to be an in-depth diagnostic analysis but rather a comprehensive technical reference for future users of these data. The MOASA air quality dataset includes 63 flight sorties (totalling over 150 h of sampling), the data from which are openly available for use. To illustrate potential uses of these upper-air observations for regional-scale model evaluation, example case studies are presented, which include analyses of the spatial scales of measured pollutant variability, a comparison of airborne to ground-based observations over Greater London and initial work to evaluate performance of the AQUM regional air quality model. These case studies show that, for observations of relative humidity, nitrogen dioxide and particle counts, natural pollutant variability is well observed by the aircraft, whereas SO2 variability is limited by instrument precision. Good agreement is seen between observations aloft and those on the ground, particularly for PM2.5. Analysis of odd oxygen suggests titration of ozone is a dominant chemical process throughout the column for the data analysed, although a slight enhancement of ozone aloft is seen. Finally, a preliminary evaluation of AQUM performance for two case studies suggests a large positive model bias for ozone aloft, coincident with a negative model bias for NO2 aloft. In one case, there is evidence that an underprediction in the modelled boundary layer height contributes to the observed biases at elevated altitudes.</p

The CogBIAS longitudinal study protocol: cognitive and genetic factors influencing psychological functioning in adolescence.

BACKGROUND: Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample. METHODS: CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships. DISCUSSION: CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.This work was supported by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement no: [324176]

Elevated Uptake of Plasma Macromolecules by Regions of Arterial Wall Predisposed to Plaque Instability in a Mouse Model

Atherosclerosis may be triggered by an elevated net transport of lipid-carrying macromolecules from plasma into the arterial wall. We hypothesised that whether lesions are of the thin-cap fibroatheroma (TCFA) type or are less fatty and more fibrous depends on the degree of elevation of transport, with greater uptake leading to the former. We further hypothesised that the degree of elevation can depend on haemodynamic wall shear stress characteristics and nitric oxide synthesis. Placing a tapered cuff around the carotid artery of apolipoprotein E -/- mice modifies patterns of shear stress and eNOS expression, and triggers lesion development at the upstream and downstream cuff margins; upstream but not downstream lesions resemble the TCFA. We measured wall uptake of a macromolecular tracer in the carotid artery of C57bl/6 mice after cuff placement. Uptake was elevated in the regions that develop lesions in hyperlipidaemic mice and was significantly more elevated where plaques of the TCFA type develop. Computational simulations and effects of reversing the cuff orientation indicated a role for solid as well as fluid mechanical stresses. Inhibiting NO synthesis abolished the difference in uptake between the upstream and downstream sites. The data support the hypothesis that excessively elevated wall uptake of plasma macromolecules initiates the development of the TCFA, suggest that such uptake can result from solid and fluid mechanical stresses, and are consistent with a role for NO synthesis. Modification of wall transport properties might form the basis of novel methods for reducing plaque rupture