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    Automated dynamic image analysis for particle size and shape classification in three dimensions

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    We introduce OCULAR, an innovative hardware and software solution for three-dimensional dynamic image analysis of fine particles. Current state-of-the art instruments for dynamic image analysis are largely limited to two-dimensional imaging. However, extensive literature has demonstrated that relying on a single two-dimensional projection for particle characterisation can lead to inaccuracies in many applications. Existing three-dimensional imaging technologies, such as computed tomography, laser scanning, and orthophotography, are limited to static objects. These methods are often not statistically representative and come with significant post-processing requirements, as well as the need for specialised imaging and computing resources. OCULAR addresses these challenges by providing a cost-effective solution for imaging continuous particle streams using a synchronised array of optical cameras. Particle shape characterisation is achieved through the reconstruction of their three-dimensional surfaces. This paper details the OCULAR methodology, evaluates its reproducibility, and compares its results against X-ray micro computed tomography, highlighting its potential for efficient and reliable particle analysis

    Barriers and facilitators to medicines use in patients with vision impairment: a theory-informed qualitative study of patients and caregivers

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    IntroductionPrevious studies have highlighted numerous challenges with medicines use for patients with vision impairment, but evidence is lacking on interventions to support safe and effective medicine use for this population. This study aimed to identify potential barriers/facilitators of medicines use from the viewpoint of patients/caregivers, to establish a theory-informed foundation for a future intervention.MethodsSemi-structured interviews were conducted with patients with vision impairment and their caregivers in Saudi Arabia. Participants were recruited from low-vision clinics and a non-profit organisation. The Theoretical Domains Framework (TDF) informed the topic guide and served as the theoretical basis for examining participants' behaviours. Interviews explored the barriers/facilitators to obtaining and taking medicines (i.e. the target behaviours). Data were analysed using the framework method and content analysis. Key TDF domains were identified by assessing the relative frequency of themes, the existence of conflicting themes and the perceived theme impact on target behaviours.ResultsTwelve patient/caregiver dyads and 18 individual patients were interviewed. Patients' ages ranged from 19 to 88 years, with 21 females and 9 males. Patients/caregivers demonstrated good knowledge of medicines used, and resourcefulness in finding methods to manage medication use (Domains: ‘Knowledge’ and ‘Skills’). ‘Environmental context and resources (ECR)’ and ‘Social influences’ were the two most coded domains. Participants reported the usefulness of several resources including pill organisers and smartphones but described problems with pharmacy environments (Domain: ‘ECR’). Caregivers played a major role in assisting patients with medicines. Participants had some positive encounters with pharmacists but reported difficulties in discussing medication issues with them. Many participants had a narrow view of the pharmacist's role (Domain: ‘Social influences’). Maintaining a routine was a major facilitator under the ‘Memory, attention and decision processes’ and ‘Behavioural regulation’ domains. Six TDF domains were considered ‘key’ to participants' behaviours.ConclusionsThis study is the first to utilise a theoretical approach to understand the behaviour of patients with vision impairment in relation to medication use. It provides a comprehensive understanding of the role of caregivers and what influences their own behaviours. Findings will inform the future development of an intervention to support safe and effective medicine use for patients with vision impairment.Patient or Public ContributionAn author met with an administrator at the ‘National Association of the Blind’ (Kafeef) in Riyadh to enhance the research team's understanding of vision impairment, and the practicality and logistics for identifying and recruiting patients. A draft of the interview guides was piloted with two patients and their caregivers and they were asked for feedback on the questions with amendments made accordingly.<br/

    Emerging technologies for ocular drug delivery

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    The article reviews the current challenges in delivering therapeutics to the eye and presents innovative strategies aimed at overcoming these barriers. It discusses traditional methods like eye drops and intravitreal injections alongside emerging solutions such as long-acting injectables, both biodegradable and non-biodegradable implants, microneedle-assisted delivery, and nanotechnology-based formulations. The review highlights how these advanced systems can improve drug bioavailability, reduce dosing frequency, and enhance patient compliance, ultimately offering promising alternatives for managing chronic ocular diseases

    Technostress of HR professionals: the darker implication of remote work transformations

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    Information and communication technologies (ICT) have facilitated an increased uptake of remote working. This research aims to understand how ICT in a remote working context affects the technostress faced by HR practitioners. Specifically, the effects of remote-working-ICT-induced technostress on work engagement, mental health, work-family conflict, and performance are examined in this study. Using the ‘EC-ST-CP-O’ (Environmental conditions-stressors-coping process-outcome) theoretical framework outlined by Tarafdar et al. (Citation2019) and conservation resource theory (COR), we have developed a moderated-mediation model and analyzed data from 218 HR practitioners from 28 software organizations in India. The analysis using PLS-SEM reveals that ICT-enabled remote work induces technostress, negatively affecting mental health, increasing work-life conflict, and reducing HR practitioners’ performance. Perceived organizational support (POS) moderates these effects. Addressing the under-researched topic of stress and well-being of HR practitioners, our study provides empirical evidence for POS in lowering the adverse effects of coping processes to manage ICT-induced technostress in the remote working context. This study contributes to the literature on ‘technostress’ in remote working contexts by researching the phenomenon of usage of ICT in organizations and its consequences and theoretically delineating ICT use on technostress in organizations

    Constant-time modulo: a secure hardware design against timing attacks

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    In the evolving landscape of cybersecurity andcryptographic hardware, it is critical to ensure resistance againsttiming side channel attacks. This paper investigates the timingside channel vulnerability in a hardware-friendly modulo algorithm. Through detailed experimental analysis, we demonstratethat the execution time of the existing implementation varies significantly with input values, making it susceptible to timing-basedattacks. To address this, we propose a constant-time moduloalgorithm that eliminates timing leakage. We further integratethis secure implementation into Number Theoretic Transform(NTT) and Inverse NTT (INTT) modules, key components insignal processing and post-quantum cryptography, and evaluatetheir performance. Our results show that while the securedesign introduces minor area and power overheads, it effectivelymitigates timing side channel risks, making it suitable for securecryptographic hardware applications

    Noninvasive genotyping and early disease dynamics demonstrate the efficacy of ibrutinib in combination with immunochemotherapy in patients with mantle cell lymphoma treated in the TRIANGLE trial

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    Adding ibrutinib to first-line immunochemotherapy (Ibru-R-chemo) showed superiority in younger mantle cell lymphoma (MCL) patients in the TRIANGLE trial (NCT02858258). To investigate response mechanisms and kinetics across treatment arms, we genotyped 57 patients from cell-free (cf)DNA using targeted-capture sequencing and investigated measurable residual disease (MRD) in cfDNA and peripheral blood by targeted-sequencing and qPCR. Pre-treatment cfDNA and circulating tumor (ct)DNA levels predicted outcomes, and precisely genotyped all patients. Circulating tumor cell (CTC)-clearance was more frequent and rapid than ctDNA-clearance across arms. At interim staging (IS), 55% of patients were ctDNA-positive while 35% and 41% were CTC-positive by qPCR and immunoglobulin gene (IG)-NGS. At end of induction, 43% were ctDNA-positive, while 15% (qPCR) and 25% (IG-NGS) were CTC-positive. MRD by qPCR was most predictive for outcomes. Ibru-R-chemo seemed to overcome TP53 -mediated risk (hazard ratio 1.9 vs. 10) and induce early MRD response, represented by enhanced CTC (71% vs. 57%) and ctDNA clearance (59% vs. 24%) at IS. Flow-cytometry-based immunomonitoring showed ibrutinib's influence on inhibitory T-cell phenotypes, showing ≥25% reduction in PD1+ and PD1+ KLRG1+ CD4+-T-cells in four patients. Taken together, besides direct anti-B-cell efficacy, ibrutinib improves chemotherapy efficiency by reconstituting an effective immune system and enhancing immune cell control

    An assessment of the functional state of endothelial colony forming cells from patients with diabetes mellitus and chronic limb threatening ischemia

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    Chronic limb threatening ischemia (CLTI) is the most severe form of peripheral vascular disease which can lead to amputation with a high associated mortality rate. Endothelial colony forming cells (ECFCs) show potential as a cell therapy to revascularize the limbs of individuals with CLTI. However, autologous ECFCs from patient peripheral blood (PB) have been reported to have a dysfunctional phenotype. We investigated this disease phenotype in individuals with CLTI, with and without diabetes mellitus (DM), to determine ECFC suitability as an autologous cell therapy. PB-ECFCs were isolated from age-matched controls, individuals with DM, and individuals with CLTI, with and without DM. The frequency of isolating ECFCs from this donor cohort was calculated. Furthermore, in vitro characterization assays were performed (growth kinetics, angiogenic properties, and reactive oxygen species [ROS] levels) and compared between donor groups. We report a significantly increased frequency of ECFCs from individuals with CLTI, with and without DM. Furthermore, our results demonstrate no significant disease related effect on the in vitro functional properties of ECFCs between cohorts. However, there is a significantly higher in vitro angiogenic capacity in individuals with DM vs age-matched controls. Our results demonstrate that ECFCs can be isolated in individuals with CLTI, with and without DM, and that ECFC functionality is similar between cohorts. Therefore, if the ∼70% isolation efficiency from both CLTI cohorts is overcome, then autologous PB-ECFCs may be a suitable therapeutic for CLTI. Further analysis is needed to determine the critical quality attributes of ECFCs from this patient population

    The influence of tablet size and weight on water-based microwave-induced in situ amorphization

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    Microwave-induced in situ amorphization is an innovative technology that enables the direct preparation of amorphous solid dispersions (ASDs) in the final dosage form. This approach offers significant advantages in addressing the challenges related to the long-term physical stability and downstream processing of ASDs. However, most previous studies have primarily focused on regular tablet sizes intended for adult patients. In light of the unique considerations and challenges associated with paediatric formulations, this study aimed to investigate the impact of tablet sizes with varying weights on microwave-induced in situ amorphization. The overall objective was to establish a novel platform for personalized formulations that cater specifically to paediatric patients with improved drug dissolution rate and enhanced patient compliance. Indomethacin (IND) was chosen as a model drug while PVP/VA 64 was selected as the polymeric carrier to prepare ASDs with 20 % (w/w) drug loading. Different-sized tablets (6 mm, 4 mm, and 2 mm which were considered as mini-tablets intended for paediatric patients) were characterized using a combination of imaging, structural and thermal analyses, followed by in vitro dissolution testing. With 2 mm mini-tablets, in particular, varying numbers of mini-tablets (one to five) were placed into an HPMC capsule which was then exposed to microwave irradiation. It was observed that a complete amorphization accompanied with an improved dissolution rate was achieved for formulations of all tablet sizes in this study. Regardless of tablet size, there were no significant differences in the extent of dissolution rate enhancement. In addition, a white-to-yellow colour change indicating amorphization of IND and a marked tablet deformation were observed in all formulations after microwaving. Among all 2 mm mini tablet formulations in capsules, the 5-in-1 formulation showed the highest amorphization rate. Overall, the in-situ amorphization platform proposed in this study can be applied to tablets with varying diameters down to 2 mm and weights down to 4 mg, indicating a promising paediatric formulation strategy

    A common garden of halichondria sponges: taxonomic revision of northeast Pacific halichondriidae reveals many cryptic introduced species

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    Sponges (phylum Porifera) possess biochemical, cellular, and physiological traits with valuable biotechnical applications. However, our ability to harness these natural innovations is limited by a classification system that does not fully reflect their evolutionary history. In this study, we uncover numerous cryptic species within the genus Halichondria that are morphologically indistinguishable from the well-known Ha. panicea. Many of these species have habitat preferences and geographic distributions that strongly suggest they have been dispersed by human activity. Most of these species are broadly sympatric with their closest relatives, and these overlapping distributions allow us to use patterns of DNA variation to infer reproductive isolation between clades in nature. With reproductively isolated species thus delineated, we can use DNA states as taxonomic characters to formally describe them. Though much remains to be learned about these newly discovered species, the natural “common gardens” of these sponges in California, New York, and other locations provide opportunities to test hypotheses about their diversification in future work

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