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Efficacy of aficamten according to geographic location of patients with hypertrophic obstructive cardiomyopathy
Get PDFBackground/Aims:
Obstructive HCM (oHCM) affects people across all geographic regions, ethnicities, and socioeconomic groups. In the SEQUOIA-HCM trial (NCT05186818), aficamten, an oral selective cardiac myosin inhibitor, improved exercise capacity, left ventricular outflow gradients (LVOT-G), and symptoms in oHCM. It is unknown if dosing, safety, or treatment response may vary by geographic region.
Methods:
Participants were randomized 1:1 to daily aficamten (5–20 mg) or placebo for 24 weeks. Participants were grouped by geographic region (North America, China, and Europe, including Israel). Baseline characteristics and treatment effects on peak oxygen uptake (pVO2) and secondary endpoints were compared across geographic groups.
Results:
In all, 282 patients were enrolled in 14 countries: 142 (50%) in Europe, including Israel; 94 (33%) in North America; and 46 (16%) in China. Patients had a higher body mass index and older age in Europe (59.7 years) and North America (61.7 years) than in China (51.8 years). More patients were New York Heart Association (NYHA) class II in Europe (81.7%) and China (93.5%) than North America (58.5%). Baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) was higher in China (82.4) than Europe (73.1) or North America (73.2). The benefit of aficamten on pVO2 was not modified by region (interaction p=0.88) and all secondary endpoints improved with aficamten treatment, acknowledging the analysis was underpowered to detect regional differences. The occurrences of serious adverse events and left ventricular ejection fraction <50% were low and similar by region.
Conclusion:
In SEQUOIA-HCM, the dosing, safety, and treatment effects of aficamten were consistent across geographic regions despite differences in baseline characteristics of patients with oHCM
Abdominal compartment syndrome after robotic-assisted thoracoscopic surgery (RATS) diaphragm plication
Get PDFDiaphragm plication is an effective treatment for diaphragmatic paralysis, in which the affected diaphragm is sutured in place. Robotic-assisted thoracoscopic (RATS) diaphragm plication combines the advantages of standard open thoracotomy and conventional thoracoscopic technique, gaining popularity as a less invasive alternative to improve the overall lung function. We present a case, to our knowledge, of the first described instance of abdominal compartment syndrome in the literature following RATS diaphragmatic plication. Abdominal compartment syndrome potentially developed as a consequence of downward hepatic shift and reduced intra-abdominal volume. This was inferred by changes in the patient’s liver enzymes and was manifested by his oliguria and raised intra-abdominal pressure. The usual treatment of abdominal compartment syndrome is debatable as it usually involves conservative decompression including percutaneous options, but definitive surgical management includes decompression of the abdomen, often by emergent laparotomy, in those with moderately elevated intra-abdominal pressure. Conservative treatment by means of supportive therapy and abdominal decompression with nasogastric tube and passing of a flatus tube was performed in our case
Making AI Evaluation Social: Group Discussion as Critical Digital Literacy Practice in EAP
No full textGenerative AI is now part of many students’ academic writing workflows, yet EAP responses often default to policy warnings or individual “prompt skills”. This short talk argues for a different starting point: making AI evaluation social. Drawing on focus group data from an EAP writing context (Groups 1–4), I show how students’ Critical Digital Literacy is enacted through collective sense-making as much as through individual verification.
Across groups, students described GenAI as helpful but limited: useful for writing initiation, outlining, summarising and language refinement, yet criticised for generic reasoning, weak disciplinary fit and unreliable citations. Crucially, the group discussion itself became a learning mechanism. As students compared outputs and strategies, they developed shared language for judging credibility, surfaced tacit norms about what counts as legitimate academic work, and negotiated boundaries between support and substitution. Talk turned general caution into actionable practices: constraining inputs, separating stylistic editing from claim checking, and treating AI text as provisional until independently verified.
I conclude with practical, discussion-based classroom approaches that create space for open and honest dialogue, and that help students practise Critical Digital Literacy in ways that transfer to independent EAP writing
AC loss prediction of HTS propulsion motors using convolutional neural network-based surrogate model for system-level modelling of electric aircraft
Get PDFSystem-level modelling, crucial for designing a
superconducting propulsion by simulating the interactive
behavior of components, faces a trade-off: simple models like lookup tables are fast but inaccurate, while detailed Finite-Element
(FE) models are accurate but too slow for system-wide studies.
This work addresses the challenge of AC loss analysis of
superconducting propulsion motors by proposing a novel deeplearning surrogate framework that delivers extremely fast and
highly accurate solutions. This enables more efficient design,
monitoring, and optimization of superconducting motors within
large-scale system models. The proposed artificial intelligencebased model benefits from integrated feature extraction powered
by Convolutional Networks, followed by a deep interconnected
neural network to grasp dynamic AC loss waveforms. This work
advances real-world applicability by enhancing time-dependent
surrogate models using data from an FE machine model. The
results demonstrate that the proposed deep neural network
captures time-dependent AC loss behavior with above 99.92%
accuracy, dynamically predicting a full AC loss waveform over a
cycle in just 3.8 milliseconds. These findings will enable advanced
system-level aircraft simulations to incorporate dynamic, highly
accurate, and ultra-fast AC loss predictions, allowing exploration
of various operating conditions encountered during flight
Compact and low cross-polarization microstrip patch antenna for 5G Internet of Things applications
Get PDFThis paper presents a miniaturization technique for microstrip patch antennas operating at the fundamental TM₀₁ mode based on a loading capacitor approach. Several gaps are inserted into the patch, and with the aid of shorting vias, coupled gaps are produced. These function as a slow-wave transmission line, and then, the operating frequency is significantly moved to a lower frequency range. The final radiating element with dimensions of approximately quarter-effective wavelength at 4.5 GHz exhibits good matching performance in the frequency range from 4.48 to 4.52 GHz and broadside gain around 5.0 dBi. It is noted that the proposed design exhibits extremely low cross-polarization radiation of less than –40 dB, which is much lower than that of the conventional quarter-wavelength patch antenna. In comparison with the reported compact patch antennas in literature, the proposed miniaturized patch is one of the smallest design with the smallest cross-polarization level, while having comparable gain. Such operation characteristics demonstrate the suitability of the proposed antenna for compact Internet of Things (IoTs) applications working at 5G New Radio n 79 band
Beyond the scales: time to prioritise treatment of obesity in psoriatic disease
No full textOverweight and obesity are significant global health problems associated with 1.6 million premature deaths each year from noncommunicable diseases such as type 2 diabetes, cancers, infections, heart disease, and stroke [1]. In psoriatic disease (PsD), increased adiposity affects many parts of the body, including the joints and skin. Notably, excess weight increases the incidence of psoriasis and psoriatic arthritis (PsA), increases disease activity, and reduces treatment response [2]. Excess weight also increases the risk of cardiometabolic comorbidities, including type 2 diabetes and cardiovascular disease, contributing to difficult-to-manage and treatment-refractory disease [3]. Weight loss is key for treating obesity and related comorbidities, with accumulating, albeit still limited, evidence of its benefit for PsD. However, achieving weight loss through lifestyle change alone is challenging. Even if successful, most patients eventually regain lost weight within a few years through a combination of physiological changes instigated by weight loss and widespread availability of highly palatable, ultra-processed foods [4]. Highly effective bariatric surgery is limited by accessibility and patient acceptability, and its effect on psoriasis and PsA disease outcomes has not been adequately studied. Novel drug approaches, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and other incretin mimetics, offer alternatives for efficacious weight loss with favourable tolerability [5]. To date, despite increasing interest over recent years, research on the mechanisms, impact, efficacy, and safety of incretin mimetics as adjunctive therapy in PsD remains scarce
A systematic review and meta-analysis of blood-based biomarkers in anal squamous cell cancer treated with chemoradiotherapy
Get PDFBackground:
Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence. Prognosis is based on clinical factors, which may not fully capture tumour biology or host immune response. Blood-based biomarkers are inexpensive, accessible, and repeatable, making them attractive prognostic tools.
Methods:
We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines (PROSPERO CRD42024547045). PubMed, EMBASE, and Web of Science were searched to July 2024 for studies reporting blood-based biomarkers in ASCC treated with curative chemoradiotherapy (CRT). Eligible studies reported overall survival (OS), disease-free survival (DFS), or locoregional control (LRC). Hazard ratios (HRs) were pooled using random-effects models when ≥ 3 studies were available per biomarker–outcome pair. Risk of bias was assessed with ROBINS-E.
Results:
Twenty-six studies (n = 3589) were included, of which 13 contributed to meta-analysis. For OS elevated neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), white cell count (WCC), and low haemoglobin (Hb) all trended toward poorer outcomes, though none reached significance. For DFS, low Hb was significantly associated with inferior survival (HR 2.69, 95 % CI 1.46–4.97), and elevated NLR predicted worse DFS (HR 1.13, 95 % CI 1.01–1.25). Additional biomarkers were described narratively, though evidence was limited.
Conclusions:
Hb and NLR show prognostic value for DFS in ASCC, while several other blood-based markers demonstrate consistent trends for OS. However, heterogeneity and small study numbers limit clinical application. These biomarkers are not yet as robust as clinicopathologic factors and prospective validation is required
The Call of the Wild and The People of the Abyss
No full textThis scholarly edition of The Call of the Wild and The People of the Abyss is one of the first set of volumes in the Oxford University Press Complete Critical Works of Jack London. It contains editions deemed to be closest to London's desired texts, based on comparison of first US and UK editions, versions published in magazines and, wherever possible, on London's manuscript and edited page proofs. The edition contains a scholarly introduction by the editor (Gair), a general introduction by a leading literary figure and Gair's scholarly notes on how and why decisions were reached in determining which text to follow at any given time
Being a liminal researcher: countering normativity through affective charges
No full textIn this article, I explore a new approach to researching dis/ability around neurodiversity differently, recentring on how my emotions and lived experiences relate to my experience as a liminal researcher. Going beyond the dichotomy of a traditional insider/outsider positionality, I consider how exploring the dynamic experience of being and becoming a liminal researcher provides possibilities to bring together debates about positionality, neurodiversity voices in research, and concerns in management and organisation studies around affect. Introducing three affective charges in the research encounter: (i) liminality as vulnerability, (ii) liminality as refocusing, and (iii) liminality as messiness, I explore how research encounters hold the potential to disrupt assumptions around the relations and reciprocities involved in researching. In doing so, I consider the potential to legitimise in-between knowledge as a new epistemological mode of studying and writing about dis/ability in organisations
Noncooperative oligopoly in markets with a continuum of traders and a strongly connected set of commodities: a limit theorem
No full textWe consider a mixed version of the Shapley window model, where large traders are represented as atoms and small traders are represented by an atomless part. In the original spirit of Cournot (1838), we partially replicate the mixed exchange economy by increasing the number of atoms, without affecting the atomless part, and ensuring that the measure space of agents remains finite. Our main theorem shows that any sequence of Cournot-Nash allocations of the strategic market games associated with the partial replications of the exchange economy has a limit point for each trader and that the assignment determined by these limit points is a Walras allocation of the original economy. Instead of relying on restrictive assumptions on the characteristics of atoms, as in Busetto et al. (2017), our limit theorem relies on the characteristics of agents in the atomless part and their endogenous price-taking behavior
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