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Tubeless automated insulin delivery versus multiple daily injections in children and adults with type 1 diabetes with elevated HbA1c (RADIANT): a multicentre, international, parallel-group, open-label, randomised, controlled trial
Get PDFBackgroundAutomated insulin delivery (AID) systems have been shown to improve glycaemic outcomes in people with type 1 diabetes managed with insulin pump therapy. No randomised studies have evaluated the benefits of tubeless AID in both adults and children with suboptimal glycaemia compared with multiple daily injections. We aimed to evaluate the safety and efficacy of a tubeless AID system compared with multiple daily injections in this population.MethodsRADIANT was a multicentre, international, parallel-group, open-label, randomised, controlled trial done in 19 hospitals in the UK, Belgium, and France. Participants aged 4–70 years with type 1 diabetes managed with multiple daily injections and continuous glucose monitoring and who had HbA1c levels of 7·5–11% (58–97 mmol/mol) were randomly assigned (2:1) to tubeless AID or control (multiple daily injections) using a permuted-block design. Participant and study teams were not masked to group allocation. The primary outcome was the adjusted between-group difference in HbA1c at 13 weeks assessed for superiority. Primary and safety outcomes were assessed in the modified intention-to-treat population (all randomly assigned participants). The study is registered with ClinicalTrials.gov, NCT05923827, and has been completed.FindingsBetween Sept 11, 2023, and April 26, 2024, 188 participants were randomly assigned to the AID group (n=125) or the control group (n=63). The AID group had a greater reduction in HbA1c, from 8·1% (SD 0·7; 65 mmol/mol [SD 7·7]) at baseline to 7·2% (0·6; 55 mmol/mol [6·6]) at 13 weeks, compared with the control group, from 8·1% (0·6; 65mmol/mol [6·6]) at baseline to 8·0% (0·7; 64 mmol/mol [7·7]) at 13 weeks, with an adjusted mean difference of –0·8% (95% CI –1·0 to –0·6; –8·7 mmol/mol [95% CI –10·9 to –6·6]; p<0·0001). During the 13-week trial, no episodes of severe hypoglycaemia or diabetic ketoacidosis occurred in either treatment group. 39 adverse events were reported among 28 participants in the AID group, and three adverse events among three participants in the control group. Two serious adverse events (Kawasaki disease and acute coronary syndrome) occurred in the AID group unrelated to the study device or procedure.InterpretationResults from this trial show the clinical efficacy of direct transition from multiple daily injections to tubeless AID in adults and children with type 1 diabetes, with no safety concerns, supporting AID as a therapeutic option within standard of care for people with type 1 diabetes
Detailed lens modeling and kinematics of the submillimeter galaxy G09v1.97: An analysis of CO, H₂O, H₂O⁺, and dust continuum emission
Get PDFContext. While the formation mechanisms of intensely starbursting galaxies at high redshift remain unknown, one possible mechanism for producing these intense rates of star formation is via mergers and interactions. However, detecting these at high redshift remains a challenge. Observations of high-redshift gravitationally lensed galaxies provide a way to study the interstellar medium and environment of these extreme starbursts in detail.Aims. We aim to use high angular resolution observations of dust continuum, CO(6−5), H2O(211 − 202), and H2O+(202 − 111) emission to constrain the ongoing processes in the z = 3.63 gravitationally lensed submillimeter galaxy H-ATLAS J083051.0+013224 (G09v1.97).Methods. We used the sophisticated lens modeling software PYAUTOLENS to perform both parametric and nonparametric source modeling. We created a demagnified source plane CO(6−5) emission line cube and performed the kinematic modeling using 3DBAROLO. Additionally, we investigated the properties of the continuum and molecular line emission in the source plane.Results. We find that the regions of CO(6−5) and H2O(211 − 202) emission are closely matched in the source plane, but that the dust continuum emission is more compact. We find that our lens modeling results do not require more than one source, contrary to what has been found in previous studies. Instead, we find that G09v1.97 resembles a rotating disk with Vmax/σ¯ = 2.8 ± 0.4, along with evidence of residual emission indicative of noncircular motions such as outflows, tidal tails, or an additional background galaxy.Conclusions. We suggest that the origin of the noncircular motions might be associated with a biconical outflow or a tidal tail from an interaction; alternatively, this might indicate the possible presence of an additional galaxy. We calculated the dynamical mass, gas mass, star formation rate, and depletion time for G09v1.97, along with a high star formation rate and low gas depletion time. In combination, this suggests that G09v1.97 has recently undergone an interaction, triggering intense star formation, while also being in the process of settling into a disk
Pet‐directed speech strengthens the veterinarian–client–patient relationship: Results from a pet owner survey
Get PDFBackgroundSeveral studies have documented veterinarians’ use of pet-directed speech (PDS). The aims of this study were to assess the use of PDS during clinic visits and the impact of PDS on pet owners’ opinions about their veterinarians.MethodsAn online survey of pet owners’ experience with, and attitudes to, PDS was conducted using snowball sampling. A descriptive statistical analysis was performed on quantitative data, and a thematic analysis was performed on free-text responses.ResultsOf the 400 respondents, almost 80% reported veterinarians using PDS. Most characterised the use of PDS as very or extremely important, and nearly 90% would more likely choose to see again a veterinarian who employed PDS. Four themes were identified from the free-text analysis: ‘pet at the centre’, ‘not just words’, ‘include the owner’ and ‘impressions of the veterinarian’.LimitationsThe limitations of the study include the potential for bias and lack of randomisation with snowball sampling, and the relatively small study sample.ConclusionPDS is widely employed by veterinarians during veterinary consultations and is valued by pet owners. Further research could help confirm the impact of PDS on the veterinarian‒client‒patient relationship and its potential for integration in veterinary communication training
Cellular and Extracellular MicroRNA Dysregulation in LRRK2-Linked Parkinson’s Disease
Get PDFCell-free microRNAs in body fluids have emerged as promising biomarker candidates in neurodegenerative diseases. While several studies have identified dysregulated miRNAs in sporadic Parkinson’s disease, it remains unclear whether distinguishable alterations of cell-free miRNAs occur in genetic forms of the disease, such as those associated with the LRRK2 G2019S mutation. In this proof-of-concept study, we used a human induced pluripotent stem cell-derived dopaminergic neuron model to investigate whether the LRRK2 G2019S mutation induces detectable changes in the intra- and extracellular miRNAome, and whether miRNA signatures identified in vitro can be validated in patient-derived cerebrospinal fluid. We differentiated dopaminergic neurons from induced pluripotent stem cells carrying the LRRK2 G2019S mutation and an isogenic gene-corrected control. Extracellular vesicles were isolated from the culture medium and used as a source of cell-free miRNA. Next, small RNA libraries were generated and analyzed. Differentially expressed microRNAs were validated in an independent batch using RT-qPCR. We further quantified candidate microRNAs in cerebrospinal fluid samples from five LRRK2 G2019S patients and matching healthy controls. The patient cohort included the fibroblast donor from whom the stem cells were originally derived. We successfully isolated extracellular vesicles from induced pluripotent stem cell-derived human dopaminergic neurons. We identified a distinct set of differentially expressed miRNAs in cellular and cell-free RNA, among which let-7g-5p and miR-21-5p were consistently upregulated and validated across independent replicates. These alterations were reflected in the cerebrospinal fluid of the original donor and partially reproduced in additional LRRK2 patients, supporting the concept of patient-specific signatures. A strong correlation between intra- and extracellular miRNA expression was observed. Our findings demonstrate that induced pluripotent stem cell-derived dopaminergic neurons can serve as a model to identify individualized, cell-free microRNA signatures associated with the LRRK2 G2019S mutation. The dysregulated miRNAs detected in vitro were mirrored in patient cerebrospinal fluid, supporting their potential as accessible molecular readouts. These results lay the groundwork for personalized biomarker strategies in genetic forms of Parkinson’s disease and warrant further validation in larger patient cohorts
Incision of the pre-Descemet layer and Descemet membrane affects outflow facility: ex-vivo studies on a human eye perfusion model
Get PDFPurpose: The collagen and elastin fibres of the pre-Descemet layer or Dua layer (PDL) fan out to become the beams of the trabecular meshwork (TM), indicating similarities in the structural elements in the PDL and TM. This study evaluated the effects of disruption of the PDL and Descemet membrane (DM) on the facility of aqueous outflow from the anterior chamber, using human eyes and an anterior segment perfusion model (ASPM). Methods: The ASPM was established using human donor eyes. The PDL and DM in the experimental eyes were half incised circumferentially along an 8 mm diameter circle for 180°, and the other half was left non-incised. Results: The experimental eyes in the ASPM model exhibited a decrease in the outflow rate, indicating an increased outflow resistance. In the TM, the expressions of fibronectin, myocilin and alpha-smooth muscle actin were increased in incised compared to non-incised and control samples. The outflow perfusates in the experimental eyes showed a significant increase in the level of active MMP-9 on day 4 and a subsequent decrease on day 9 compared to the control eyes. Myocilin was only detected in the perfusate on day 9 in the experimental eyes. Conclusion: Our study suggests that surgical disruption of the PDL and DM results in decreased outflow, which can be due to an alteration in biomechanical properties, with consequent molecular changes in the TM, adversely affecting the resistance to outflow. This could explain why the incidence of raised pressure is greater with penetrating keratoplasty compared to deep anterior lamellar keratoplasty
Developing and evaluating the patient’s perspective of needling questionnaire for haemodialysis
Get PDFBackgroundCannulation of vascular access for haemodialysis is essential when using arteriovenous access. However, this can be a painful and distressing procedure for patients. There is no current measure that enables inclusion of patients’ experiences of cannulation as an outcome in research comparing interventions to improve cannulation. This study aimed to develop a patient reported outcome measure of cannulation for haemodialysis, focusing on the physical and psychological experiences of patients. This was named the ‘Patient’s Perspective of Needling’ (PPN) questionnaire.MethodologyThe PPN was developed with six patient representatives. Face validity assessed understandability, relevance and comprehensiveness of the PPN. Convergent validity assessed the correlation of the PPN results to the Short-Form Vascular Access Questionnaire (SF-VAQ). Internal consistency and test-retest reliability tested the reliability of the PPN. Floor and ceiling effects were examined and the interpretation of the results of the PPN were explored by: (a) using an item discrimination index; (b) calculating the smallest detectable change. Free text comments were analysed using basic thematic analysis.ResultsThe first version of the PPN underwent face validity testing with 12 participants from two renal centres, which led to further amendments of the PPN. The final PPN contained three sections with 17 questions, on pain, worry and problems. Internal consistency of the final PPN was 0.937 (n = 98, 95% CI 0.917–0.954, p < 0.0001). For convergent validity, a correlation to Question 3 of SF-VAQ was − 0.347 (95% CI -0.146 - -0.521, p < 0.001) and Question 4–15 of SF-VAQ was 0.613 (95% CI 0.450–0.736, p < 0.001). Test-retest reliability was 0.856 (95% CI 0.788–0.904, p < 0.001). The smallest detectable change was 0.135. The Pain section of the PPN scored the highest, with the Worry and Problems sections scoring lower. Free text comments from the PPN expanded on difficulties with cannulation, showing that cannulation experience varied over time and how patients cope with cannulation.ConclusionsThe PPN behaved in a valid and reliable manner for the tests completed, enabling patients’ experiences of cannulation to be included as an outcome in research studies into cannulation for haemodialysis
An experimental investigation of unique high stepup boost converter for electric vehicle and solar photovoltaic
Get PDFHigh step-up DC–DC converters are essential in electric vehicle (EV) and photovoltaic (PV) applications, where low-voltage inputs must be efficiently boosted to higher levels. Conventional converters suffer from high switching losses, bulky components, and unstable regulation under dynamic conditions. To address these challenges, this paper proposes a compact transformer based high step-up boost (HGB) converter integrated with an SG3525 PWM controller and an analog proportional–integral (PI) compensation network. The novelty of the design lies in the jointly optimized transformer winding structure (20-gauge/8-turns primary, 32-gauge/176-turns secondary with center tap) and robust analog PI compensation, which together achieve high gain with reduced duty ratio stress and stable voltage regulation. A hardware prototype was developed and tested under both programmable DC source and real PV input conditions. Experimental results confirm that the converter reliably steps up 12 V to 200 V DC, with efficiency consistently close to 90% across load levels from 5.6 W to 40 W. Gate pulses and switching behavior were validated through simulation, showing correct complementary drive at 50 kHz and safe device stress margins. Ripple analysis further shows that inductor current ripple remains below 15%, and capacitor voltage ripple remains below 2%, ensuring smooth operation. The converter also demonstrated strong linear gain response, maintaining duty ratios between 60% (at 8.5 V input) and 40% (at 12 V input). Real-time PV tests confirmed regulated output under fluctuating irradiation, with voltages ranging from 140 V to 225 V. These results establish the proposed converter as an efficient, compact, and experimentally validated solution for renewable energy systems and EV powertrains
Why safety recommendations don't (always) work: understanding the problems and exploring some solutions
Get PDFBackground: Safety recommendations are one of the most widely used tools for translating analysis of safety issues into improvement actions, but can sometimes complicate and confuse rather than support systemic safety improvement efforts. Methods: This paper explores the range of problems that can limit the effectiveness and impact of safety recommendations, and uses these problems as a basis for articulating a set of guiding principles which may support more systematic and robust approaches to making and monitoring safety recommendations. Results: One of the most notable problems with safety recommendations in healthcare is the enormous quantity and abundance of recommendations that are produced, which can overwhelm those who are expected to act on them. Other problems include a lack of rigour in identifying and analysing the safety risks that recommendations aim to address, variability in specifying the risks to be addressed and the improvements to be achieved, and limited integration or connection between recommendations. Recommendations can also be inappropriately used as a management tool, can become confused with orders or requirements for compliance and can have little supporting infrastructure for ensuring system improvements actually result. Conclusions: This paper explores these problems and argues that addressing these problems requires systematic and robust processes for defining the risks that need to be targeted by recommendations, as well as more sophisticated governance systems for supporting coordinated improvement activities. A set of eight principles is proposed, which can support a more systematic, integrated and robust approach to developing and using safety recommendations
Experimental Investigation of a Highly Loaded Half-Journal Bearing
Get PDFA dedicated experimental rig is presented for a half-journal bearing operating under highly loaded, well-controlled hydrodynamic lubrication conditions relevant to turbomachinery. The apparatus combines pressure measurements in the film, distributed temperature measurements in the shaft and bush, and ultrasonic film-thickness measurements that map the circumferential film-thickness profile across the lubrication region. Experiments are reported for normal loads of 5–20 kN and shaft speeds of 1000–4000 rpm with controlled oil supply conditions. The measured pressure and temperature trends are consistent with established hydrodynamic lubrication behaviour. The film thickness measurements confirm full-film operation across the tested operating envelope, while indicating increased uncertainty in regions affected by cavitation. A correlation for the temperature rise due to viscous heating is proposed as a compact representation of the data. The rig design and accompanying measurements provide a benchmark-quality data set intended for validation and development of thermal elasto-hydrodynamic lubrication (TEHL)/computational fluid dynamics (CFD) models under high load and speed conditions
Investigation of End Winding Vibration Characteristics, Insulation Failure, and Protection in FESS
No full textThe permanent magnet synchronous motor/generator serves as the critical component for energy conversion in the flywheel energy storage system (FESS), and stator end winding insulation constitutes the important factor affecting system reliability and lifespan. Through the-oretical analysis, finite element analysis, and experimental verification, this article studies the vibration characteristics and insulation damage of end windings in FESS. First, the coupling model of end winding vibration is established considering the stator magnetic pull per unit area (MPPUA) and winding electromagnetic force (EF), and the stress intensity factor (SIF) is introduced to characterize the insulation damage behavior. Then, the vibration of the winding during charge, standby and discharge of FESS is calculated by field-circuit coupling and multiphysics coupling analysis, and the experimental verification is carried out. Finally, the SIF analysis of the crack is carried out using the transient structure field, and the experimental equipment is set up to complete the strain measurement of different end winding parts and the local reinforcement analysis. The methods and results of this article provide reference and guidance for the design, manufacture and maintenance of FESS
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