Ion-doped brushite cements for bone regeneration

Decades of research in orthopaedics has culminated in the quest for formidable yet resorbable biomaterials using bioactive materials. Brushite cements most salient features embrace high biocompatibility, bioresorbability, osteoconductivity, self-setting characteristics, handling, and injectability properties. Such type of materials is also effectively applied as drug delivery systems. However, brushite cements possess limited mechanical strength and fast setting times. By means of incorporating bioactive ions, which are incredibly promising in directing cell fate when incorporated within biomaterials, it can yield biomaterials with superior mechanical properties. Therefore, it is a key to develop fine-tuned regenerative medicine therapeutics. A comprehensive overview of the current accomplishments of ion-doped brushite cements for bone tissue repair and regeneration is provided herein. The role of ionic substitution on the cements physicochemical properties, such as structural, setting time, hydration products, injectability, mechanical behaviour and ion release is discussed. Cell-material interactions, osteogenesis, angiogenesis, and antibacterial activity of the ion-doped cements, as well as its potential use as drug delivery carriers are also presented.This study was funded by the Portuguese Foundation for Science and Technology (FCT) and the German Academic Exchange Service (Deutscher Akademischer Austauschdienst, DAAD) for the transnational cooperation FCT/DAAD 2018-2019. The authors also thank the funds provided under the distinctions attributed to JMO (IF/01285/2015) and SP (CEECIND/03673/2017). Furthermore, funding by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), Grant Nr. HU 2498/1-1; GB 1/22-1, and the Emerging Talents Initiative of the FAU is acknowledged

On the principal bifurcation branch of a third order nonlinear long-wave equation

We study the principal bifurcation curve of a third order equation which describes the nonlinear evolution of several systems with a long--wavelength instability. We show that the main bifurcation branch can be derived from a variational principle. This allows to obtain a close estimate of the complete branch. In particular, when the bifurcation is subcritical, the large amplitude stable branch can be found in a simple manner.Comment: 11 pages, 3 figure

First-principles study of As interstitials in GaAs: Convergence, relaxation, and formation energy

Convergence of density-functional supercell calculations for defect formation energies, charge transition levels, localized defect state properties, and defect atomic structure and relaxation is investigated using the arsenic split interstitial in GaAs as an example. Supercells containing up to 217 atoms and a variety of {\bf k}-space sampling schemes are considered. It is shown that a good description of the localized defect state dispersion and charge state transition levels requires at least a 217-atom supercell, although the defect structure and atomic relaxations can be well converged in a 65-atom cell. Formation energies are calculated for the As split interstitial, Ga vacancy, and As antisite defects in GaAs, taking into account the dependence upon chemical potential and Fermi energy. It is found that equilibrium concentrations of As interstitials will be much lower than equilibrium concentrations of As antisites in As-rich, $n$-type or semi-insulating GaAs.Comment: 10 pages, 5 figure

Bistability of Slow and Fast Traveling Waves in Fluid Mixtures

The appearence of a new type of fast nonlinear traveling wave states in binary fluid convection with increasing Soret effect is elucidated and the parameter range of their bistability with the common slower ones is evaluated numerically. The bifurcation behavior and the significantly different spatiotemporal properties of the different wave states - e.g. frequency, flow structure, and concentration distribution - are determined and related to each other and to a convenient measure of their nonlinearity. This allows to derive a limit for the applicability of small amplitude expansions. Additionally an universal scaling behavior of frequencies and mixing properties is found. PACS: 47.20.-k, 47.10.+g, 47.20.KyComment: 4 pages including 5 Postscript figure

Early Detection of Prostate Cancer: The Role of Scent

Prostate cancer (PCa) represents the cause of the second highest number of cancer-related deaths worldwide, and its clinical presentation can range from slow-growing to rapidly spreading metastatic disease. As the characteristics of most cases of PCa remains incompletely understood, it is crucial to identify new biomarkers that can aid in early detection. Despite the prostate-specific antigen serum (PSA) levels, prostate biopsy, and imaging representing the actual gold-standard for diagnosing PCa, analyzing volatile organic compounds (VOCs) has emerged as a promising new frontier. We and other authors have reported that highly trained dogs can recognize specific VOCs associated with PCa with high accuracy. However, using dogs in clinical practice has several limitations. To exploit the potential of VOCs, an electronic nose (eNose) that mimics the dog olfactory system and can potentially be used in clinical practice was designed. To explore the eNose as an alternative to dogs in diagnosing PCa, we conducted a systematic literature review and meta-analysis of available studies. PRISMA guidelines were used for the identification, screening, eligibility, and selection process. We included six studies that employed trained dogs and found that the pooled diagnostic sensitivity was 0.87 (95% CI 0.86–0.89; I2, 98.6%), the diagnostic specificity was 0.83 (95% CI 0.80–0.85; I2, 98.1%), and the area under the summary receiver operating characteristic curve (sROC) was 0.64 (standard error, 0.25). We also analyzed five studies that used an eNose to diagnose PCa and found that the pooled diagnostic sensitivity was 0.84 (95% CI, 0.80–0.88; I2, 57.1%), the diagnostic specificity was 0.88 (95% CI, 0.84–0.91; I2, 66%), and the area under the sROC was 0.93 (standard error, 0.03). These pooled results suggest that while highly trained dogs have the potentiality to diagnose PCa, the ability is primarily related to olfactory physiology and training methodology. The adoption of advanced analytical techniques, such as eNose, poses a significant challenge in the field of clinical practice due to their growing effectiveness. Nevertheless, the presence of limitations and the requirement for meticulous study design continue to present challenges when employing eNoses for the diagnosis of PCa

Pattern formation in directional solidification under shear flow. I: Linear stability analysis and basic patterns

An asymptotic interface equation for directional solidification near the absolute stabiliy limit is extended by a nonlocal term describing a shear flow parallel to the interface. In the long-wave limit considered, the flow acts destabilizing on a planar interface. Moreover, linear stability analysis suggests that the morphology diagram is modified by the flow near the onset of the Mullins-Sekerka instability. Via numerical analysis, the bifurcation structure of the system is shown to change. Besides the known hexagonal cells, structures consisting of stripes arise. Due to its symmetry-breaking properties, the flow term induces a lateral drift of the whole pattern, once the instability has become active. The drift velocity is measured numerically and described analytically in the framework of a linear analysis. At large flow strength, the linear description breaks down, which is accompanied by a transition to flow-dominated morphologies, described in a companion paper. Small and intermediate flows lead to increased order in the lattice structure of the pattern, facilitating the elimination of defects. Locally oscillating structures appear closer to the instability threshold with flow than without.Comment: 20 pages, Latex, accepted for Physical Review

Eutectic Colony Formation: A Stability Analysis

Experiments have widely shown that a steady-state lamellar eutectic solidification front is destabilized on a scale much larger than the lamellar spacing by the rejection of a dilute ternary impurity and forms two-phase cells commonly referred to as `eutectic colonies'. We extend the stability analysis of Datye and Langer for a binary eutectic to include the effect of a ternary impurity. We find that the expressions for the critical onset velocity and morphological instability wavelength are analogous to those for the classic Mullins-Sekerka instability of a monophase planar interface, albeit with an effective surface tension that depends on the geometry of the lamellar interface and, non-trivially, on interlamellar diffusion. A qualitatively new aspect of this instability is the occurence of oscillatory modes due to the interplay between the destabilizing effect of the ternary impurity and the dynamical feedback of the local change in lamellar spacing on the front motion. In a transient regime, these modes lead to the formation of large scale oscillatory microstructures for which there is recent experimental evidence in a transparent organic system. Moreover, it is shown that the eutectic front dynamics on a scale larger than the lamellar spacing can be formulated as an effective monophase interface free boundary problem with a modified Gibbs-Thomson condition that is coupled to a slow evolution equation for the lamellar spacing. This formulation provides additional physical insights into the nature of the instability and a simple means to calculate an approximate stability spectrum. Finally, we investigate the influence of the ternary impurity on a short wavelength oscillatory instability that is already present at off-eutectic compositions in binary eutectics.Comment: 26 pages RevTex, 14 figures (28 EPS files); some minor changes; references adde

En bloc resection of bladder tumour: the rebirth of past through reminiscence

Purpose: To learn about the history and development of en bloc resection of bladder tumour (ERBT), and to discuss its future directions in managing bladder cancer. / Methods: In this narrative review, we summarised the history and early development of ERBT, previous attempts in overcoming the tumour size limitation, consolidative effort in standardising the ERBT procedure, emerging evidence in ERBT, evolving concepts in treating large bladder tumours, and the future directions of ERBT. / Results: Since the first report on ERBT in 1980, there has been tremendous advancement in terms of its technique, energy modalities and tumour retrieval methods. In 2020, the international consensus statement on ERBT has been developed and it serves as a standard reference for urologists to practise ERBT. Recently, high-quality evidence on ERBT has been emerging. Of note, the EB-StaR study showed that ERBT led to a reduction in 1-year recurrence rate from 38.1 to 28.5%. An individual patient data meta-analysis is currently underway, and it will be instrumental in defining the true value of ERBT in treating non-muscle-invasive bladder cancer. For large bladder tumours, modified approaches of ERBT should be accepted, as the quality of resection is more important than a mere removal of tumour in one piece. The global ERBT registry has been launched to study the value of ERBT in a real-world setting. / Conclusion: ERBT is a promising surgical technique in treating bladder cancer and it has gained increasing interest globally. It is about time for us to embrace this technique in our clinical practice

Master Equation Study of Hydrogen Relaxation Using Complete Sets of State-to-state Transition Rates

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97096/1/AIAA2012-362.pd

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette–Guerin Immunotherapy

Background: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette–Guérin (BCG) therapy. Methods: We retrospectively reviewed patient’s medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models. Results: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; p = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; p = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression (p = 0.076). Kaplan–Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92–94), in patients with mGPS 0, 82.2% (CI 95% 78.9–85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4–70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97–99) in patients with mGPS 0, 90% (CI 95% 87–94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study. Conclusions: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion