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Fast Gradient Methods for Data-Consistent Local Super-Resolution of Medical Images
Get PDFIn this work, we propose a new paradigm of iterative model-based reconstruction algorithms for providing real-time solution for zooming-in and refining a region of interest in medical and clinical tomographic images. This algorithmic framework is tailored for a clinical need in medical imaging practice that after a reconstruction of the full tomographic image, the clinician may believe that some critical parts of the image are not clear enough, and may wish to see clearer these regions of interest. A naive approach (which is highly not recommended) would be to perform the global reconstruction of a higher resolution image, which has two major limitations: first, it is computationally inefficient, and second, the image regularization is still applied globally, which may over-smooth some local regions. Furthermore, if one wishes to fine-tune the regularization parameter for local parts, it would be computationally infeasible in practice for the case of using global reconstruction. Our new iterative approaches for such tasks are based on jointly utilizing the measurement information, efficient up-sampling/down-sampling across image spaces, and locally adjusted image prior for efficient and high-quality post-processing. The numerical results in low-dose X-ray CT image local zoom-in demonstrate the effectiveness of our approach
Diabetes management using a clinical guideline versus usual practice:a feasibility trial-based qualitative study among Ayurvedic practitioners and patients in Nepal
Get PDFBackground: Type 2 diabetes mellitus (T2DM) is common in Nepal, where many people seek primary care through Ayurveda, a widely practiced traditional medical system. However, concerns remain about variability in clinical practice and the quality of care provided by Ayurvedic practitioners. No evidence-based clinical practice guideline (EB-CPG) currently exists for managing T2DM in Ayurveda. To address this, an EB-CPG was developed, and a feasibility trial was conducted to inform a future definitive cluster randomized controlled trial evaluating whether the EB-CPG would improve T2DM management compared to usual clinical practice. Objectives: To explore the experiences and perspectives of Ayurvedic practitioners and patients regarding the two treatment groups (EB-CPG-based care versus usual clinical practice) and participation in the feasibility trial. Design: Constructivist qualitative study. Methods: Semistructured interviews were conducted with Ayurvedic practitioners and patients. Data were analyzed thematically using an inductive approach and the framework method. Results: A total of 41 Ayurvedic practitioners and patients were interviewed. Common themes identified across both groups included facilitators and challenges in the trial patient recruitment, challenges in usual clinical care, experiences with EB-CPG-based care (predominantly positive), ease and difficulties of monthly follow-ups, and pros and cons of patient diaries for assessing medication compliance. Practitioner-specific themes included the diverse populations they serve; patients’ motivations for choosing Ayurveda over Western medicine; their motivations for trial participation; balancing clinical duties with the trial demands; confusion about trial roles and responsibilities; and other trial-related issues such as understanding processes and documentation, support and communication, coordination with data collectors, and finances and other resources. Conclusion: The EB-CPG-based approach for managing T2DM by Ayurvedic practitioners in Nepal was well-received and perceived as more beneficial than usual clinical practice. Trial experiences and perspectives were largely positive; however, several challenges related to trial conduct should be addressed in future studies, including the definitive cluster trial
Ultrasound-Responsive Nanoparticles Enable Hydrophobic Antibiotic Release and Deep Penetration for Biofilm Treatment
Get PDFLocalized delivery of antibiotics is a promising strategy that leads to transformative treatment pathways of bacterial biofilms and increases the effectiveness of their administration in contrast to traditional delivery methods requiring high antibiotic doses. Hydrophobic antibiotics have poor activity against bacterial biofilms due to their limited penetration and are particularly challenging to deliver. Nanoparticles are ideal drug delivery agents to achieve spatially controlled delivery, but commonly their designs are either soft or porous, which limits temporally triggered release, with the result that most of the antibiotic does not reach deeply into the biofilm. In this study, we present designs of nonporous silica nanoparticles that encapsulate a lipophilic antibiotic, rifampicin, with noncovalent interactions and enable controlled release triggered by Low-Frequency Ultrasound (LFUS). Staphylococcus aureus biofilms treated with the nonporous, core@shell, rifampicin-encapsulated nanoparticles, RIF⊂PhSiO2@SiO2, combined with LFUS, achieved 90% biofilm eradication, compared to 20% without ultrasound; treatment with free rifampicin and LFUS resulted only in a 10% reduction. Nanoparticle penetration into biofilm layers was visualized using fluorescent nanoparticles prepared with coencapsulation of the Nile red fluorophore, RIF+NR⊂PhSiO2@SiO2. Confocal fluorescence imaging of the biofilms demonstrated penetration of the nanoparticles throughout all the layers of the biofilm upon LFUS application, in sharp contrast to their presence in only the top few biofilm layers without LFUS. Scanning Electron Microscopy of the biofilms confirmed the presence of nanoparticles and the dual role of LFUS in promoting penetration and facilitating drug release by disrupting molecular interactions within the nanoparticle. This work introduces a design paradigm for nonporous nanoparticle agents combined with ultrasound, enabling both temporal and spatial control of drug release in bacterial biofilms. This will open transformative therapeutic approaches for effective localized delivery of drugs that have previously been challenging to deliver
Physical Frailty and Sarcopenia in Liver Transplantation:How Should They Be Assessed and Addressed?
No full textPhysical frailty and sarcopenia are increasingly associated with morbidity and 2-fold mortality in patients with advanced chronic liver disease awaiting liver transplantation (LT). Furthermore, they significantly affect post-LT recovery and patients’ ability to return to independent daily living, including employment. The increased prevalence of metabolic risk factors (ie, obesity, diabetes) and the aging population have contributed to the prevalence of physical frailty and the complexity of the multidisciplinary team decision-making that surrounds LT. Therefore, it is essential that physical frailty is identified early in the LT clinical pathway to provide targeted nutritional (1.2–2.0 g/kg protein intake, pancreatic exocrine replacement therapy) and individualized exercise (both aerobic and resistance) interventions in the form of (p)rehabilitation. A variety of clinical tools currently exist to assess the nutritional status of LT recipients, sarcopenia, and physical frailty, including patient questionnaires (ie, Royal Free Hospital Global Assessment, Duke Activity Status Index), easy-to-use “by the bedside” tests (ie, liver frailty index, 6-min walk test), and the more specialist investigations (ie, computer tomography, cardiopulmonary exercise testing). This overview aims to briefly summarize these tools, focusing on their varying ease of use, accessibility, and efficacy in a field that lacks consensus and continuity among LT centers. In addition, the overview highlights the benefits and future challenges of implementing pre- and post-LT rehabilitation programmes.</p
The effects of stress ratio and temperature on fatigue behavior of an epoxy adhesive
Get PDFEpoxy adhesives are widely used in outdoor structural applications for bonding, where they are often subjected to cyclic loading patterns at different environmental temperatures, nevertheless, their synergistic effect on fatigue behavior has not yet been fully experimentally investigated. This study examined the tension–tension fatigue behavior of a structural epoxy at stress ratios (R) of 0.1, 0.5 and 0.9 and temperatures of 20 °C, 40 °C and 55 °C, where the onset glass transition temperature (Tg-onset) was 49 °C. At each temperature, increasing R extended fatigue life, particularly at 20 °C. This effect was slightly reduced at 40 °C, particularly at R = 0.9, because creep was accelerated at high temperature. At R = 0.5 and R = 0.9, fatigue life decreased with increasing temperature, while at R = 0.1, little change was observed when temperature increased from 20 °C to 40 °C. At 55 °C, exceeding Tg-onset, fatigue life significantly decreased across all stress ratios due to thermal softening. Stiffness degradation was predominantly attributed to damage initiation resulted from cyclic loading and thermal softening at elevated temperature, while creep effect was very limited, as observed at R = 0.9. The measured total energy dissipation for cyclic loading and creep exhibited that the contribution of creep increased with temperature. Finally, the constant life diagrams were formulated using a linear model by connecting the constant life points at R = 0.1 and R = 0.9, which showed good agreement at R = 0.5
Structural covariance network topology in individuals at clinical high risk for psychosis:the ENIGMA-CHR Study
Get PDFBrain network architecture is anticipated to influence future grey matter loss in individuals at Clinical High Risk (CHR) for psychosis. However, existing studies on grey matter structural network properties in CHR are scarce and constrained by small sample sizes. Here, we examined network topology differences comparing a) CHR versus healthy controls (HC); b) CHR who transitioned to psychosis (CHR-T) versus those who did not (CHR-NT); and c) different subsyndromes. We included structural scans from 1842 CHR individuals and 1417 HC individuals from 31 sites within the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. At the global level, CHR individuals exhibited lower structural covariance (q < 0.001; Cohen’s d = 0.164) and less optimal structural network configuration than HC (lower global efficiency and clustering coefficient, d = 0.100,0.087, qs <= 0.027). Though no global difference between CHR-T and CHR-NT, network distinctiveness of the frontal and temporal surface area networks was higher in CHR-T than CHR-NT (d = 0.223,0.237) and HC (d = 0.208,0.219) (qs < 0.001). Network distinctiveness of the frontal cortical thickness network was lower in CHR-T (d = 0.218, q < 0.001) than CHR-NT and HC (d = 0.165, q < 0.001). Importantly, higher network distinctiveness was associated with worse positive symptoms in CHR-NT (frontal surface area, q = 0.008, R2 = 0.013) and at trend with worse negative symptoms in CHR-T (frontal thickness, q = 0.063, R2 = 0.049). Further, the brief intermittent psychotic syndrome subgroup showed more severe network alterations. Together, brain structural networks inform symptoms and the risk of transition to psychosis in CHR individuals
Optimised clinical protocol for root canal obturation using single cone and hydraulic cement sealer
Get PDFIntroduction This study aimed to establish an optimised clinical protocol based on matching the root canal preparation, irrigation and obturation by choosing an adequate that prepared the dentin and reduced the microbial load followed by a root canal obturation that maintained the seal. Methods A split tooth model was used to assess the irrigation and obturation quality. Three irrigation sequences including sodium hypochlorite, EDTA and HEDP with water used as a control. Four commercial sealers (AH Plus, BioRoot RCS, BioRoot Flow and TotalFill) were used to obturate the root canal using single cone obturation technique. The ultrastructure and chemical properties of the dentin and sealers and the dentin-sealer interface were assessed before and after obturation and contact with the irrigation sequences using scanning electron microscopy, energy dispersive spectroscopy, and Fourier transform infrared spectroscopy. Microbiological analysis by direct contact test and minimum inhibitory concentration was undertaken with and without dentin contact. All results were analysed using a two-way ANOVA and Tukey post hoc tests (p < 0.05). Results Irrigation with HEDP resulted in less erosion of dentin and a larger mineral concentration zone at the interface of hydraulic cements with dentin. Furthermore, continuous chelation with HEDP improved the antimicrobial properties of the hydraulic cement sealers. All sealers exhibited a reduction in their antimicrobial effectiveness when in contact with irrigated dentin. Conclusions The irrigation techniques affected the interfacial characteristics and antimicrobial properties of root canal sealers, indicating that a selection of appropriate irrigation protocols for clinical practice is required to optimize treatment outcomes
Senescence-related myocardial dysfunction:keeping a young heart
Get PDFThe heart, a vital organ, works without interruption and constantly adjusts to the ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the heart is determined by the health of the myocardium, which undergoes changes with ageing that are both under-investigated and incompletely understood, potentially impacting our approach to pathological conditions. Here, the alterations in cellular, tissue, and gross physiological function of the heart with age are discussed. At the molecular level, non-coding RNAs influence cellular senescence, and extracellular vesicles induce fibrosis through matrix remodelling. Mitochondrial dysfunction and altered fatty acid oxidation reduce cellular energetics, whilst accumulation of reactive oxygen species and steatosis, as well as telomere shortening coupled with reduced autophagy, limit the myocardium's regenerative capability. Loss of cardiomyocytes, combined with senescence, requires compensatory hypertrophy, inducing myocardial stiffness and altered muscle function. In addition to these direct alterations in myocardial characteristics with ageing, other factors that can affect the myocardium indirectly are addressed, including valve calcification, resulting in regurgitation and/or stenosis; vascular abnormalities, reducing compliance and exacerbating hypertension; fibrosis leading to cardiac arrhythmias; and autonomic dysregulation, reducing cardiac adaptability. Finally, potential modulation of cardiac ageing is discussed whilst also addressing which senescent modifications should be considered as ageing-related physiological changes of the myocardium. A better understanding of myocardial ageing will differentiate physiological changes from early, preventable, and reversible pathological changes, consequently helping to optimize management of individuals with or at risk of myocardial disease by taking into account diverse trajectories of myocardial ageing.</p
Off-design operation of grid-scale pumped thermal energy storage:A comparative analysis of control strategies
Get PDFThis work explores and compares control strategies to enable off-design operation of grid-scale pumped thermal energy storage (PTES) systems. Four relevant control strategies are identified to provide this kind of operational flexibility: inventory control, variable speed operation, flow control with bypass valves, and variable turbomachine geometry. These are applied to a comprehensive system model of a 100MW, 10h commercial PTES concept. The system model is characterised by a dynamic consideration of the thermal reservoirs, off-design performance models for all components and a more detailed description of electrical components. Each control strategy’s operating range and its impact on component performance, system performance, and electrical energy capacity are quantified. The findings indicate that none of the strategies cover the entire operating range. Inventory control is confirmed as the most promising strategy, covering 61.4% of the theoretical nominal operating range, without significant performance loss. Variable speed covers 38.6% of the nominal operating range and shows performance drops in off-design. Bypassing the turbine enables limited flexibility on the charging side and covers the lowest operating range (22.1%). Bypass control can only modulate the discharging power by incurring high losses. Variable compressor inlet guide vanes have a similar effect to variable speed, covering 30.7% of the operating range, but at a much lower cost. Variable speed, turbine bypass, and variable compressor inlet guide vanes significantly alter the cycle’s specific work; this, in turn, causes temperature fluctuations in the liquid storage tanks. Temperature fluctuations in one cycle can affect subsequent cycles, making those control options less attractive as stand-alone options
Nanoscale Mechanics of FnBPB-Mediated Adhesion of <i>Staphylococcus aureus</i> to Skin Ligands
No full textStaphylococcus aureus commonly colonizes human skin, impairing barrier integrity and increasing the risk of diseases such as atopic dermatitis (AD). The staphylococcal fibronectin-binding protein B (FnBPB) engages in attachment to the skin, yet little is known about the interaction mechanisms of its two functional regions: an N-terminal A domain responsible for fibrinogen-specific binding, and a C-terminal domain composed of fibronectin-binding repeats (FnBRs). Here, we combine atomic force microscopy with the use of isogenic S. aureus strains expressing wild-type FnBPB or domain-specific mutants to dissect the individual contributions of the A domain and FnBRs to two key skin ligands, fibrinogen (Fg) and fibronectin (Fn). Force spectroscopy with bacterial probes reveals that both functional regions play critical roles in mediating the adhesion of S. aureus to healthy and AD corneocytes. Force spectroscopy with Fg- or Fn-functionalized tips shows that FnBPB binds Fg via a stress-activated dock, lock, and latch (DLL) mechanism, with forces up to ∼2 nN, while Fn engages in both weak bonds (∼0.1 nN) and strong, force-dependent tandem β-zipper interactions (∼0.8 nN). In the absence of FnBRs, the lifetime and stability of Fg bonds are greatly reduced, suggesting this domain contributes to the bond stability. In addition, the A domain not only governs Fg DLL interaction but also assists Fn-binding. Collectively, our findings provide a biophysical foundation for the multifunctional adhesion properties of FnBPB during skin colonization, being able to bind multiple ligands using a complex synergy of interactions
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