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In situ monitoring of the annealing process using Spatially Resolved Acoustic Spectroscopy
Get PDFAnnealing heat treatments lead to microstructural transformation, but such transformations have rarely been observed in situ. Spatially Resolved Acoustic Spectroscopy is a non-destructive technique for imaging microstructure, which is fast enough to image dynamic changes in the sample. This study demonstrates the in situ monitoring of the annealing process that includes the recovery, recrystallisation and grain growth. The microstructural changes are observed by measuring the surface acoustic wave velocities, allowing the grain evolution to be monitored
Efficacy and safety of minocycline in patients with acute ischaemic stroke (EMPHASIS): a multicentre, double-blind, randomised controlled trial
Get PDFBackgroundMinocycline has been reported as a multi-target anti-neuroinflammatory drug with potential benefits for ischaemic stroke in preclinical models and small-scale clinical studies. The EMPHASIS trial was designed to provide robust evidence regarding its efficacy and safety in patients with acute ischaemic stroke.MethodsA multicentre, double-blind, randomised, placebo-controlled trial was conducted at 58 hospitals across China. Patients who had an ischaemic stroke in the previous 72 h with a National Institutes of Health Stroke Scale (NIHSS) score ranging from 4 to 25 and a level of consciousness score (subscale 1a of the NIHSS) of 1 or less were randomly assigned in a 1:1 ratio to receive minocycline or placebo in addition to routine treatment. Minocycline (loading dose of 200 mg, followed by 100 mg every 12 h for the subsequent 4 days) or matching placebo was administered orally. Block randomisation with a fixed block size of four stratified by study site was done with a computer-generated randomisation sequence. All patients, treating clinicians, and investigators involved in the trial were fully masked to treatment allocation. The primary outcome was an excellent functional outcome at 90 days (with a modified Rankin Scale [mRS] score of 0–1) and was analysed in all patients who were randomised and received at least one dose of the study drug, without imputation for missing data. Safety outcomes were assessed in participants who received at least one dose of the study drug and had at least one safety evaluation and included symptomatic intracranial haemorrhage at 24 h and 6 days. This trial was registered with ClinicalTrials.gov (NCT05836740) and is now completed.FindingsBetween May 19, 2023, and May 20, 2024, 1724 patients were randomly assigned to minocycline (n=862) or placebo (n=862) groups. Median age was 65 years (IQR 57–71). 1151 (66·8%) patients were male and 573 (33·2%) were female. Median NIHSS score at baseline was 5 (IQR 4–7). Four patients withdrew consent (three in the minocycline group and one in the placebo group) and 19 patients were lost to follow-up (nine in the minocycline group and ten in the placebo group). At 90 days, 447 (52·6%) of 850 patients with minocycline and 403 (47·4%) of 851 with placebo had an mRS score of 0–1 (adjusted risk ratio 1·11, 95% CI 1·03–1·20; p=0·0061). Ordinal analysis across the full range of mRS scores also favoured minocycline, with an adjusted common odds ratio of 1·19 (95% CI 1·03–1·38; p=0·018). The incidence of symptomatic intracranial haemorrhage was similar between the minocycline and placebo groups at 24 h (1/860 [0·1%] vs 0/861 [0%]) and 6 days (3/859 [0·3%] vs 0/861 [0%]). No significant differences were observed in other safety outcomes, including serious adverse events (40/862 [4·6%] in the minocycline group vs 51/862 [5·9%] in the placebo group; p=0·24).InterpretationMinocycline therapy initiated within 72 h of acute ischaemic stroke provided a significant functional outcome benefit compared with placebo at 90 days, without safety concerns. Future studies are needed to confirm these findings and to establish whether the benefits extend to patients with more severe or minor strokes.FundingNational Natural Science Foundation of China, Beijing Healthunion Cardio-cerebrovascular Disease Prevention and Treatment Foundation, Noncommunicable Chronic Diseases—National Science and Technology Major Project, Beijing Municipal Science & Technology Commission, Chinese Institutes for Medical Research, Capital's Funds for Health Improvement and Research, and National Key R&D Program of China
Surgery in Older Cancer Patients
Get PDFPurpose of Review: This narrative review explores the evolving role of surgery in older adults with cancer, highlighting non-operative and minimally invasive alternatives, and the integration of geriatric principles to improve selection of treatment and postoperative outcomes. Recent Findings: Minimally invasive and non-operative treatments can provide comparable oncological outcomes to traditional surgery with lower morbidity and better functional recovery. Frailty screening tools aid in predicting postoperative outcomes, and geriatric assessment can identify vulnerabilities and assist treatment planning, prehabilitation and rehabilitation. Prehabilitation, early rehabilitation, and multidisciplinary collaboration enhance recovery and align care with patient values and outcomes that matter most. Summary: Surgical care in older cancer patients is shifting toward a model focused on preserving quality of life and personalised decision-making. Incorporating geriatric assessments and less invasive approaches can improve outcomes and reduce treatment burden. Further research is needed to integrate these strategies into standard practice
Human Beta Oscillations Reflect Magnitude and Fidelity of Priority Shifts in Working Memory
Get PDFFlexible prioritisation in working memory (WM) is supported by neural oscillations in frontal and sensory brain areas, but the roles of different oscillations remain poorly understood. Recordings in humans suggest an interplay between prefrontal slow frequency (2-8Hz) and posterior alpha-band (10Hz) oscillations regulating top-down control and retrieval of WM representations, respectively. Complementary work, primarily in non-human primates, suggests an additional role for beta (15-30Hz) oscillations in clearing or inhibiting stimuli from entering WM. Here we investigated the role of neural oscillations in prioritising WM content using electroencephalography (EEG) as participants (humans of any sex) performed a task requiring frequent priority switches between two memorized oriented bars. Behavioural performance revealed switch costs, which scaled with the angular distance between the two items, suggesting that priority shifts are modulated by shift magnitude. Time-frequency analyses revealed increased frontal theta (4–8Hz) and decreased central-parietal beta (15–25Hz) power during switches. Crucially, only beta power scaled with the magnitude of the priority shift and predicted the fidelity of neural decoding of the newly prioritized item during subsequent recall. Theta power, by contrast, was elevated on switch trials but did not vary with update magnitude or decoding strength, suggesting a more general role in signaling control demands. Our findings highlight a particular and previously overlooked role for beta-band oscillations in the flexible prioritisation of WM content
Designing a Framework to Support Practice-Based Interprofessional Education Initiatives for Student Pharmacists: A Modified Delphi Study
Get PDFObjective To determine consensus among key stakeholders on statements to design a framework supporting practice-based interprofessional education (IPE) initiatives for student pharmacists. Methods The study used a 2-round modified Delphi technique. Statements were developed from published literature, a document analysis of international IPE frameworks, and findings from empirical studies completed as part of a wider program of research. This study was underpinned by the 3P (Presage-Process-Product) Model of Classroom Learning. A 4-point Likert scale was used. Data were analyzed using descriptive statistics. Consensus was preset at ≥70% agreement for individual statements. Panelists could provide comments at the end of each section; these were analyzed thematically. The Robert Gordon University School Ethics Review Committee granted ethical approval. Results Forty-five panelists consented to participate; a response rate of 82.2% (37/45) was achieved in round 1 and 71.1% (32/45) in round 2. In round 1, consensus was reached on 70/75 (93.3%) statements/substatements. In round 2, consensus was reached on 9/11 (81.8%) statements; 5 statements that did not achieve consensus in round 1, and 6 new statements based on panel members’ comments. The 2 statements that did not reach consensus related to summative assessment. Two themes were identified: “Realistic versus idealistic approach?” and “Looking at the bigger picture.” Conclusion Key stakeholders agree on the majority of presage, process, and product factors that must be considered during the development of practice-based IPE initiatives. Further investigation is needed to clarify any factors potentially contributing to a lack of agreement on statements relating to assessment
Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial (Baby-OSCAR trial)
Get PDFBackground: In extremely preterm babies, born before 28 weeks’ gestation, a large (≥ 1.5 mm in diameter) patent ductus arteriosus present beyond 3 days of age is associated with higher mortality and morbidity than infants without a patent ductus arteriosus. The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus. Whether selective early treatment of a large patent ductus arteriosus with ibuprofen improves health and developmental outcomes is not known. Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled trial evaluating early treatment (≤ 72 hours after birth) with ibuprofen for a large patent ductus arteriosus in extremely preterm infants. The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia at 36 weeks’ of post menstrual age. The short-term secondary outcomes included complications of prematurity, patent ductus arteriosus closure and side effects of treatment. The main long-term outcome was survival without moderate or severe neurodevelopmental impairment, using parent report or classified by blinded end-point review committee at 24 months of corrected age. Other secondary outcomes included survival without respiratory morbidity and duration of oxygen supplementation. A health economic evaluation was undertaken. Results: A total of 326 infants were randomised to ibuprofen and 327 to placebo. The primary outcome occurred in 220/318 infants (69.2%) in the ibuprofen group and in 202/318 infants (63.5%) in the placebo group (adjusted risk ratio 1.09, 95% confidence interval 0.98 to 1.20; p = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died by 36 weeks of gestation (adjusted risk ratio 1.32, 95% confidence interval 0.92 to 1.90). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. At 24 months of corrected age, outcome data were available for 263 and 274 children in the ibuprofen and placebo groups, respectively. Survival without moderate to severe neurodevelopmental impairment in the ibuprofen and placebo groups was 131/248 (53.0%) and 134/259 (51.9%), respectively; adjusted risk ratio 1.01 (95% confidence interval 0.86 to 1.18); p = 0.901. Survival without respiratory morbidity was 66/210 (31.4%) and 74/220 (33.6%), respectively; adjusted risk ratio 0.92 (95% confidence interval 0.70 to 1.20); p = 0.536. Median duration of oxygen supplementation was 76.0 and 78.0 days, respectively. Conclusion: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of post menstrual age was not statistically significantly lower for extremely preterm infants randomised to early treatment with ibuprofen compared to placebo. There was no evidence of an improvement in survival without moderate to severe neurodevelopmental impairment or survival without respiratory morbidity at 24 months’ corrected age, after selective early treatment of a large patent ductus arteriosus with ibuprofen in children born extremely preterm. Future work: Future work required includes a trial in babies who are clinically symptomatic and fail to close the patent ductus arteriosus beyond 7 days of age; an individual patient data meta-analysis; follow-up of babies in Baby-OSCAR at 8–10 years of age. Limitations: Open-label therapy was received by 29.8% of infants in the placebo group, potentially increasing the percentage of infants with patent ductus arteriosus closure in this group. The first dose of trial treatment was administered at a median of 61 hours after birth, later than in other trials
Three-Phase Multilevel DC/AC Converter and Synergetic Modulation for Split Batteries
No full textThis letter introduces a three-phase multilevel converter for the integration of multiple battery submodules. The circuit comprises a synergetic modulated quasi-single stage design that includes a three-phase three-level voltage source converter operating at low switching frequency and two modular series-connected half-bridge converters operating with high switching frequency. Therein, all dc-link voltage rated devices switch at low frequency and zero voltage while sinusoidal currents are ensured without a complicated control. Furthermore, it provides a multilevel conversion and consequently smaller voltage transients enhancing power quality. In addition, the modular configuration enables flexible management of the series-connected battery submodules, eliminating the need for an extra balancer between the battery submodules. This letter provides an explanation of circuit operation and the synergistic modulation technique. Simulations and experimental results are presented to validate the feasibility of the proposed circuit
Stimuli-activatable protein degraders for targeted cancer therapy: from prodrug design to nanoplatform applications
Get PDFDisruption of proteostasis represents a critical pathological mechanism driving tumorigenesis and progression. Proteolysis targeting chimera (PROTAC) and molecular glue operating via the ubiquitin-proteasome pathway have created new therapeutic paradigms by enabling precise elimination of disease-associated proteins. These technologies not only overcome the constraints of traditionally “undruggable” targets but also enable sustained modulation through “event-driven” mechanism. Despite these advantages, conventional degraders still face limitations such as off-target effects and suboptimal pharmacokinetic profiles. In response, stimuli-activatable degradation platforms have emerged, integrating smart activatable elements to confer spatiotemporal control over degradation activity within the tumor microenvironment. The combined platform of prodrug and nanodelivery system enhanced degrader solubility, prolonged circulation half-life, and enabled tumor-selective accumulation with controllable release. This strategy improved therapeutic efficacy while reducing systemic toxicity. By enabling coordinated regulation of degradation initiation, localization, and termination, such chemical strategies provided a foundation for developing next-generation intelligent degraders with improved precision and reduced toxicity. This review systematically examined stimuli-activatable molecular designs applied to PROTAC, evaluated their roles in achieving tumor-selective protein degradation, and discussed future directions for clinical translation
A Radio Frequency Interference Detection and Analytical Geolocation Method Demonstrated from LEO with an End-To-End Simulator and CYGNSS Raw Data
Get PDFRadio frequency interference (RFI) presents a growing threat to applications, ranging from surveying and construction to remote sensing and GNSS reflectometry (GNSS-R). RFI inevitably degrades the quality of GNSS-R observation data and data inversion. Due to ongoing geopolitical conflicts, the need to detect and geolocate these RFI sources worldwide has been increasing. This paper presents an analytical method based on the Doppler shift and Doppler rate measurements using a single Low Earth Orbit (LEO) satellite to detect and geolocate RFI transmitters. The methods are demonstrated using RFI-simulated data generated with the Orolia Skydel GNSS simulator and validated against historical Cyclone GNSS (CYGNSS) raw IF data. The geolocation method provides an unambiguous, converged, and stable solution through an optimisation process that estimates the location of the RFI transmitter. The RFI detection method is based on the short-time Fourier transform (STFT), which is robust in low signal-to-noise ratio (SNR) environments, operating reliably down to -35 dB. The geolocation method is computationally efficient, operating on short data windows (30-60 seconds) and accommodating different types of interference. Two CYGNSS raw IF datasets were selected for detection and geolocation. The geolocation algorithm produced a converged and consistent estimated RFI transmitters at the global minimum of the cost function, while also providing accurate vertical positioning of the RFI sources through the use of the Copernicus GLO-30 Digital Elevation Model (DEM). The geolocation accuracy for the simulated RFI scenarios was approximately within (20-50) meters, while for overhead scenarios it was 800 meters, reflecting the sensitivity of the analytical model that has been addressed in this paper. The end-to-end simulation allows assessments of the accuracy in a variety of scenarios, while the CYGNSS raw data demonstrate the method and techniques applied to current in-orbit data
An Observational Study of the Energy and Sugar Content of Drinks and Snacks Available in UK Coffee Shops and Cafés
Get PDFObjective: To examine the proportion of drinks and snacks offered by the largest coffee shop chains in the UK that exceed the NHS and Public Health England maximum recommended intakes for energy and sugar. Design: Observational study design where nutritional information for drinks and snacks was gathered from the official coffee shop chain website. Data were compared with the maximum recommended intakes of 200 kcal per drink or snack and 30 g of free sugar per day. Direct comparisons between mean values were performed using analysis of variance (ANOVA). Subjects: A total of 2707 drinks and 434 snacks across eight leading coffee shop chains in the United Kingdom. Results: Overall, 47.0% of drinks and 66.8% of snacks exceed the recommended energy intake, while 32.5% of drinks and 45.3% of snacks surpass the recommended daily free sugar intake. 'Hot chocolates and other speciality drinks' contain the most energy (255.6 ± 5.78 kcal) of all drink categories. Snacks contain significantly more energy than drinks (p < 0.001), with all three snack categories exceeding the recommended intake of energy. Variations in nutritional content were observed in dairy-alternative milk options and specific chains. Conclusions: The high energy and sugar content of drinks and snacks in major UK coffee chains may contribute to excessive energy intake, with almost half of all drinks and snacks exceeding the maximum recommended levels. Healthier choices, such as avoiding flavoured drinks or limiting the consumption of snacks, may be necessary to help mitigate weight gain and combat obesity and T2DM rates in the UK
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