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The role of the antidiabetic drug metformin in prostate cancer has long been ambiguous. Our study reveals that metformin can provide clinical benefit for prostate cancer patients only when NKX3.1 expression is low, where it inhibits oxidative stress–mediated disease progression. The antidiabetic drug metformin has known anticancer effects related to its antioxidant activity; however, its clinical benefit for prostate cancer (PCa) has thus far been inconclusive. Here, we investigate whether the efficacy of metformin in PCa is related to the expression status of NKX3.1 , a prostate-specific homeobox gene that functions in mitochondria to protect the prostate from aberrant oxidative stress. To investigate the relationship of NKX3.1 expression and metformin efficacy in PCa. Functional studies were performed in vivo and in vitro in genetically engineered mouse models and human LNCaP cells, and organotypic cultures having normal or reduced/absent levels of NKX3.1. Correlative studies were performed using two independent retrospective tissue microarray cohorts of radical prostatectomies and a retrospective cohort of prostate biopsies from patients on active surveillance. Metformin was administered before or after the induction of oxidative stress by treatment with paraquat. Functional endpoints included analyses of histopathology, tumorigenicity, and mitochondrial function. Correlative endpoints include Kaplan-Meier curves and Cox proportional hazard regression models. Metformin reversed the adverse consequences of NKX3.1 deficiency following oxidative stress in vivo and in vitro, as evident by reduced tumorigenicity and restored mitochondrial function. Patients with low NKX3.1 expression showed a significant clinical benefit from taking metformin. Metformin can overcome the adverse consequences of NKX3.1 loss for PCa progression by protecting against oxidative stress and promoting normal mitochondrial function. These functional activities and clinical correlates were observed only with low NKX3.1 expression. Thus, the clinical benefit of metformin in PCa may depend on the status of NKX3.1 expression. Prostate cancer patients with low NKX3.1 are likely to benefit most from metformin treatment to delay disease progression in a precision interception paradigm. [ABSTRACT FROM AUTHOR]

The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential biomarker in SLE, but its association with several outcomes remains unclear. We aimed to evaluate the relationship between NLR and SLE disease activity, damage, depression, and health-related quality of life. A cross-sectional study was conducted, including 134 patients with SLE who visited the Division of Rheumatology between November 2019 and June 2021. Demographics and clinical data including NLR, Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus disease activity index (SELENA–SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), physician global assessment (PhGA), patient global assessment (PGA), patient health questionnaire (PHQ)-9, patient self-rated health, and lupus quality of life (LupusQoL) scores, were collected. Patients were stratified into two groups and compared using the NLR cut-off of 2.73, the 90th percentile value of healthy individuals. The analysis included t-test for continuous variables, χ2-test for categorical variables, and logistic regression adjusting for age, sex, BMI, and glucocorticoid use. Among the 134 SLE patients, 47 (35%) had an NLR ≥ 2.73. The NLR ≥ 2.73 group had significantly higher rates of severe depression (PHQ ≥ 15), poor/fair self-rated health, and the presence of damage (SDI ≥ 1). These patients also scored significantly lower in LupusQoL domains (physical health, planning, and body image), and higher in SELENA-SLEDAI, PhGA, and PGA. Logistic regression confirmed that high NLR is associated with severe depression (PHQ ≥ 15) (OR:7.23, 2.03–25.74), poor/fair self-rated health (OR:2.77,1.29–5.96), high SELENA-SLEDAI score(≥ 4) (OR:2.22,1.03–4.78), high PhGA (≥ 2) (OR:3.76, 1.56–9.05), and presence of damage (SDI ≥ 1) (OR:2.67, 1.11–6.43). High NLR in SLE may indicate depression, worse quality of life, active disease, and the presence of damage. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the prevalence and the clinical significance of lymphadenopathy and its histological subtypes in patients with systemic lupus erythematosus. We conducted a retrospective cohort study of patients with SLE diagnosed using the 1997 ACR criteria, who were followed at our institution between 2008 and 2022. Patients were grouped based on the presence of SLE-attributed LAD and its histological phenotype, then compared in terms of demographic, clinical and laboratory characteristics. Of the 255 patients, 33.7% had SLE-attributed, 0.8% lymphoma-related and 0.4% tuberculosis-related LAD. Univariate analysis identified significant associations between the presence of LAD and fever (p < 0.0001), weight loss (p = 0.009), pericarditis (p = 0.004), myocarditis (p = 0.003), myositis (p = 0.034), leukopenia (p = 0.004), lymphopenia (p = 0.003), membranous nephritis (p = 0.004), anti-RNP (p = 0.001), anti-Smith (p = < 0.0001), and SSB antibodies (p = 0.038), and hypocomplementemia (C3:p = 0.019; C4:p < 0.0001). Logistic regression confirmed the associations of LAD with fever (OR = 3.277, 95% C.I 1.657–6.481), pericarditis (OR = 4.146, 95% C.I:1.577–10.899), membranous nephritis (OR = 3.586, 95% C.I:1.305–9.854), and leukopenia (OR = 2.611, 95%C.I:1.319–5.166), but not with weight loss, myocarditis, or myositis. Biopsy in a subset of patients (33.7% of total) revealed reactive/proliferative (62.1%) or necrotizing (37.9%) histological patterns. When we compared the histologic patterns, necrotizing LAD was associated with fever (p = 0.052), sicca (p = 0.018), and malar rash (p = 0.005). Most patients received corticosteroids, hydroxychloroquine, and/or DMARDs with relatively quick clinical improvement. In conclusion, LAD is a common SLE manifestation, associated with constitutional symptoms, myo-/pericarditis, myositis, cytopenia, and membranous nephritis. Despite relatively high prevalence of LAD in SLE, a biopsy may still be needed to rule out lymphoma. [ABSTRACT FROM AUTHOR]

Extra virgin olive oil (EVOO) possesses a high-value rank in the food industry, thus making it a common target for adulteration. Hence, several methods have been essentially made available over the years. However, the issue of authentication remains unresolved with national and food safety organizations globally struggling to regulate and control its market. Over the course of this study, the aim was to determine the origin of EVOOs suggesting a high-throughput, state-of-the-art method that could be easily adopted. A rapid, NMR-based untargeted metabolite profiling method was applied and complemented by multivariate analysis (MVA) and statistical total correlation spectroscopy (STOCSY). STOCSY is a valuable statistical tool contributing to the biomarker identification process and was employed for the first time in EVOO analysis. Market samples from three Mediterranean countries of Spain, Italy, and Greece, blended samples from these countries, as well as monocultivar samples from Greece were analyzed. The NMR spectra were collected, with the help of chemometrics acting as "fingerprints" leading to the discovery of certain chemical classes and single biomarkers that were related to the classification of the samples into groups based on their origin. [ABSTRACT FROM AUTHOR]

Carotid atherosclerosis is a major cause for stroke, with significant associated disease burden morbidity and mortality in Western societies. Diagnosis, grading and follow-up of carotid atherosclerotic disease relies on imaging, specifically ultrasound (US) as the initial modality of choice. Traditionally, the degree of carotid lumen stenosis was considered the sole risk factor to predict brain ischemia. However, modern research has shown that a variety of other imaging biomarkers, such as plaque echogenicity, surface morphology, intraplaque neovascularization and vasa vasorum contribute to the risk for rupture of carotid atheromas with subsequent cerebrovascular events. Furthermore, the majority of embolic strokes of undetermined origin are probably arteriogenic and are associated with nonstenosing atheromas. Therefore, a state-of-the-art US scan of the carotid arteries should take advantage of recent technical developments and should provide detailed information about potential thrombogenic (/) and emboligenic arterial wall features. This manuscript reviews recent advances in ultrasonographic assessment of vulnerable carotid atherosclerotic plaques and highlights the fields of future development in multiparametric arterial wall imaging, in an attempt to convey the most important take-home messages for clinicians performing carotid ultrasound. [ABSTRACT FROM AUTHOR]

Foodomics employs advanced analytical techniques to provide answers regarding food composition, authenticity control, marker identification and issues related to food quality and safety. Nuclear magnetic resonance (NMR) spectroscopy and chromatography hyphenated to mass spectrometry (MS) are the main analytical platforms used in this field. Nevertheless, they are rarely employed in an integrated manner, and even then, the contribution of each technique remains vague. Table olives (Olea europaea L.) are a food commodity of high economic and nutritional value with an increasing production tendency over the last two decades, which, however, suffers from extensive fraud incidents and quality determination uncertainties. Thus, the current attempt aims towards two axes with the first being the multilevel integration of LC-HRMS and NMR data of the same samples and table olives being the selected matrix. In more detail, UPLC-HRMS/MS-based analysis was compared at different stages within an untargeted metabolomics workflow with an NMR-based study and the complementarity of the two platforms was evaluated. Furthermore, statistical heterospectroscopy (SHY), rarely employed in foodomics, combining the spectroscopic with spectrometric datasets and aiming to increase the confidence level of annotated biomarkers was applied. Amongst these lines, the second parallel axis of this study was the detailed characterization of table olives' metabolome in search for quality markers considering the impact of geographical (from Northern to Southern Greece) and botanical origin (Kalamon, Konservolia, Chalkidikis cultivars), as well as processing parameters (Spanish, Greek). To that end, using deep dereplication tools including statistical methods, with SHY employed for the first time in table olives, different biomarkers, belonging to the classes of phenyl alcohols, phenylpropanoids, flavonoids, secoiridoids and triterpenoids were identified as responsible for the observed classifications. The current binary pipeline, focusing on biomarkers' identification confidence, could be suggested as a meaningful workflow not only in olive-based products, but also in food quality control and foodomics in general. [Display omitted] • In-depth characterization of table olives via untargeted UPLC-HRMS/MS and chemometrics. • Quality markers correlated to geographical/botanical origin and processing parameters. • Step-by-step integration of LC-HRMS/MS and NMR data in a multilevel approach. • Statistical heterospectroscopy (SHY) methods rarely employed in foodomics. • Suggestion of a binary and detailed workflow for the food quality assessment. [ABSTRACT FROM AUTHOR]

Systemic Lupus Erythematosus (SLE) and lupus nephritis treatment is still based on non-specific immune suppression despite the first biological therapy for the disease having been approved more than a decade ago. Intense basic and translational research has uncovered a multitude of pathways that are actively being evaluated as treatment targets in SLE and lupus nephritis, with two new medications receiving FDA approval in the last 3 years. Herein we provide an overview of targeted therapies for SLE including medications targeting the B lymphocyte compartment, intracellular signaling, co-stimulation, and finally the interferons and other cytokines. • Non-specific immune-suppression are still used for the treatment of Systemic Lupus Erythematosus and lupus nephritis. • Medications targeting B cells, Type I Interferons and Calcineurin have recently been approved for the treatment of SLE and LN. • Actively evaluated therapeutic targets include BLyS/APRIL, CD19/CD20, Jak, dendritic cells and co-stimulatory molecules. [ABSTRACT FROM AUTHOR]

Objective Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis of the middle-size vessels, confined to the skin. We conducted a systematic review in order to identify studies evaluating the different treatment modalities used in CPAN. Methods This systematic review was conducted according to PRISMA guidelines, registered in PROSPERO: CRD42020222195. PubMed/Medline databases were searched from inception to December of 2020 using the terms: (Polyarteritis nodosa[Title/Abstract]) AND ((therapy[Title/Abstract]) OR (management[Title/Abstract]) OR (treatment[Title/Abstract]))' and 'Cutaneous arteritis [Title/Abstract]'. Articles evaluating pertaining to the management of CPAN in adults were eligible for inclusion. Results A total of seven eligible case series with 325 unique patients were included. No study included a control population. In general, systemic corticosteroids were widely used as induction treatment. Immunosuppressive agents combined with corticosteroids were AZA, hydroxychloroquine, sulfasalazine, sulphapyridine, CYC, MTX, mycophenolate, tacrolimus, rituxima and thalidomide. Other agents utilized in the studies were dapsone, colchicine, non-steroid anti-inflammatory drugs, salicylates, warfarin and clopidogrel. In some studies, the presence of ulcerations was associated with an increased risk of relapse. Conclusion The evidence available regarding the management of patients with CPAN is limited at best. Further studies are needed in order to evaluate the effect of treatment on disease remission, relapses and mortality. [ABSTRACT FROM AUTHOR]

• Metallorganic antibiotics. • New antitumor and antimicrobial agents. • Organotin micelles. Sodium Lauryl Sulphate (SLS) and Cetyltrimethylammonium bromide (CTAB) were employed to create micelles (SLS@CIPTIN and CTAB@CIPTIN) of the organometallic antibiotic Ph 2 Sn(CIP) 2 (CIPTIN) (where HCIP= ciprofloxacin). The characterization of the micelles was conducted in the solid-state using melting point, Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR), 119Sn Mössbauer and X-ray Fluorescence (XRF) spectroscopies, and Thermogravimetry/Differential Thermal Analysis (TG-DTA), while in solution, by Ultra violet-Visible (UV–Vis) and Nucleus Magnetic Resonance (1HNMR) spectroscopic techniques were employed. The compounds were tested for their antiproliferative activity against human breast adenocarcinoma cells: MCF-7 (hormone depended (HD)) and MDA-MB-231 (hormone independent (HI)). The in vitro and in vivo non-genotoxicity was confirmed with micronucleus (MN) and Artemia salina assay. The antiproliferative mechanism of action of SLS@CIPTIN and CTAB@CIPTIN was studied by cell morphology and cell cycle arrest. The antibacterial activity was evaluated using Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZ) against Minimum Bactericidal Concentration (MBC) against Gram-negative strains P. aeruginosa, E. coli , as well as Gram-positive strains S. epidermidis and S. aureus. The results indicate that both the investigated CIPTIN and its supramolecular assembly (SLS@CIPTIN) exhibit activity. Therefore, the encapsulation of antimicrobial compounds can indeed be regarded as an attractive strategy for the development of new dual-active agents. These agents offer concurrent anticancer and antibacterial attributes without inducing toxicity. [Display omitted] Surfactants like SLS and CTAB were utilized in the formation of micelles (SLS@CIPTIN and CTAB@CIPTIN) containing the organometallic antibiotic Ph 2 Sn(CIP) 2 (CIPTIN), where HCIP = ciprofloxacin. Antimicrobial and antiproliferative investigations demonstrate that an integrated approach can combine the metallorganic-antibiotic CIPTIN and its micellar variant, SLS@CIPTIN , providing simultaneous anticancer and antibacterial properties without causing toxicity. [ABSTRACT FROM AUTHOR]

The article reports that ultrasound is the first-line modality for the diagnostic approach of carotid disease with a role in screening, grading and following-up carotid atherosclerosis after conservative or surgical treatment. Topics include examines the technological advances observed and the emergence of new technologies such as contrast-enhanced ultrasound and elastography have further augmented the technique's capabilities and potential in this setting.

The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most commonly diagnosed cancer in men worldwide, which is almost incurable, once it progresses into the metastatic stage. Adriamycin (ADR) is a known chemotherapeutic agent that causes severe side effects. In recent years, studies in natural plant products have revealed their anticancer activities. In particular, Glycyrrhiza glabra enhanced extract (GGE), commonly known as licorice, has been reported to exert antiproliferative properties against cancer cells. In this study, the cytotoxic potential of GGE was assessed in PC-3 cells, when it is administrated alone or in combination with Adriamycin. PC-3 cells were treated with GGE and/or ADR, and the inhibition of cell proliferation was evaluated by the MTT assay. Cell cycle alterations and apoptosis rate were measured through flow cytometry. Expression levels of autophagy-related genes were evaluated with specific ELISA kits, Western blotting, and real-time PCR, while NMR spectrometry was used to identify the implication of specific metabolites. Our results demonstrated that GGE alone or in co-treatment with ADR shows antiproliferative properties against PC-3 cells, which are mediated by both apoptosis and autophagy mechanisms. [ABSTRACT FROM AUTHOR]

Abstract In glioblastoma, the benefit from temozolomide chemotherapy is largely limited to a subgroup of patients (30–35%) with tumors exhibiting methylation of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene. In order to allow more patients to benefit from this treatment, we explored magnetic resonance image-guided microbubble-enhanced low-intensity pulsed focused ultrasound (LIFU) to transiently open the blood-brain barrier and deliver a first-in-class liposome-loaded small molecule MGMT inactivator in mice bearing temozolomide-resistant gliomas. We demonstrate that a liposomal O6-(4-bromothenyl)guanine (O6BTG) derivative can efficiently target MGMT, thereby sensitizing murine and human glioma cells to temozolomide in vitro. Furthermore, we report that image-guided LIFU mediates the delivery of the stable liposomal MGMT inactivator in the tumor region resulting in potent MGMT depletion in vivo. Treatment with this new liposomal MGMT inactivator facilitated by LIFU-mediated blood-brain barrier opening reduced tumor growth and significantly prolonged survival of glioma-bearing mice, when combined with temozolomide chemotherapy. Exploring this novel combined approach in the clinic to treat glioblastoma patients with MGMT promoter-unmethylated tumors is warranted. Graphical abstract Unlabelled Image Highlights • A novel therapeutic liposomal agent inactivates MGMT in glioblastoma • MRI-guided LIFU opens the BBB to deploy nanotherapeutics in targeted regions • LIFU-driven delivery of liposomal MGMT inactivators reverses glioma chemoresistance [ABSTRACT FROM AUTHOR]

The prevalence of neural networks in applications is expanding at an increasing rate. It is becoming clear that providing robust guarantees on systems that use neural networks is very important, especially in safety-critical applications. A trained neural network's sensitivity to adversarial attacks is one of its greatest shortcomings. To provide robust guarantees, one popular method that has seen success is to describe and bound the activation functions in the neural network using equality and inequality constraints. However, there are numerous ways to form these bounds, providing a trade-off between conservativeness and complexity. We approach the problem from a different perspective, using sparse polynomial optimisation theory and Positivstellensatz, a key result in real algebraic geometry. The former exploits the natural cascading structure of the neural network using ideas from chordal sparsity while the latter tests the emptiness of a semi-algebraic set using algebra, to provide tight bounds. We show that bounds can be tightened significantly, whilst the computational time remains reasonable. We compare the solve times of different solvers and show how accuracy can be improved at the expense of increased computation time. In particular, we show that with the sparse polynomial framework the solve time and accuracy can be improved over other methods for neural network verification, for networks with ReLU, sigmoid and tanh activation functions. [ABSTRACT FROM AUTHOR]

Commercial milk formulae hold a major role in the diet of many infants in developed countries and assessing their mineral content is important in order to ensure compliance with the manufacturer claims and with regulation guidelines. In this study, the concentrations of K, Ca, Fe, Zn, Br, Rb and Sr were determined by Energy-Dispersive X-Ray Fluorescence (EDXRF) spectrometry in 28 infant milk formulae widely distributed in the Greek market. The concentration ranges (in mg kg −1 ) measured for K (2180–7600), Ca (3240–7480), Fe (29–98) and Zn (38–84) were within the limits recommended by the European legislation, with only a few exceptions. Although measured values were generally consistent with those labelled by the manufacturers, discrepancies over 50% to 100% were observed in some cases and were analyzed by multivariate statistical methods. The findings indicate the need for close monitoring to guarantee good manufacturing practices and constant quality of infant formulae. The daily intakes of minerals from consumption of different types of milk formulae were also estimated and the overall ranges were (0.23–0.85) g d −1 for K, (348–736) mg d −1 for Ca, (3.2–10.5) mg d −1 for Fe and (4.1–9.0) mg d −1 for Zn. These values conform to currently recommended safety limits. [ABSTRACT FROM AUTHOR]

Liposomal delivery is a well-established approach to increase the therapeutic index of drugs, mainly in the field of cancer chemotherapy. Here, we report the preparation and characterization of a new liposomal formulation of a derivative of lomeguatrib, a potent O 6 -methylguanine-DNA methyltransferase (MGMT) inactivator. The drug had been tested in clinical trials to revert chemoresistance, but was associated with a low therapeutic index. A series of lomeguatrib conjugates with distinct alkyl chain lengths – i.e. C12, C14, C16, and C18 – was synthesized, and the MGMT depleting activity as well as cytotoxicity were determined on relevant mouse and human glioma cell lines. Drug-containing liposomes were prepared and characterized in terms of loading and in vitro release kinetics. The lipophilic lomeguatrib conjugates did not exert cytotoxic effects at 5 μM in the mouse glioma cell line and exhibited a similar MGMT depleting activity pattern as lomeguatrib. Overall, drug loading could be improved by up to 50-fold with the lipophilic conjugates, and the slowest leakage was achieved with the C18 derivative. The present data show the applicability of lipophilic lomeguatrib derivatization for incorporation into liposomes, and identify the C18 derivative as the lead compound for in vivo studies. [ABSTRACT FROM AUTHOR]

Fresh-cut vegetables became more and more popular due to healthy eating habits, with main problem safety of the product because of microbial spoilage as well as visual and nutritional quality changes. Ozone may act as a sanitizer; however, due to its strong oxidant activity care is needed, as in some cases, that is, if the dose being used is too high, the quality of the produce may be reduced. In this study, ozonated water at various concentrations and dipping times (0, 0.4, 0.8, or 1.2 mg/L for 0, 1, 15, or 30 s) were tested. Results revealed that application of ozonated water (0.8 mg/L for 30 s) before packaging reduced yellowing and maintained compositional characteristics of the fresh-cut spinach leaves, ensuring a shelf-life extension of 3 days. Moreover, a positive effect on microbial population control was recorded during the first 5 days of storage. Practical applications The use of chlorine or other chemicals in fresh-cut industry is decreasing while alternatives treatments are proposed. Ozone even had remarkable antimicrobial action however because of its oxidation action could be negative for the horticultural products. This work investigated the efficiency of ozone treatment (concentration and dipping time) to control yellowing of fresh-cut spinach as well as the effect on microbial counts and leaves composition. The information obtained from this study provide the chance to extend the postharvest life of a highly perishable product with an alternative to chemical treatment that could be easily applied in processing line. [ABSTRACT FROM AUTHOR]

Not applicable. [ABSTRACT FROM AUTHOR]

The evolution of ultrasound (US) techniques has greatly improved the evaluation of many parameters in dialysis vascular access, which is typically achieved through an arteriovenous fistula (AVF) or graft (AVG). These techniques include grayscale B-mode, color Doppler, power Doppler, spectral Doppler, non-Doppler US flow imaging techniques, contrast-enhanced US, and elastography. In conjunction with a patient's medical history and physical examination, US provides crucial information about the native vascular bed prior to the surgical creation of an arteriovenous anastomosis. It also tracks the maturation progress of the newly created AVF or AVG and aids in diagnosing potential complications of the vascular access. These complications include thrombosis, steal syndrome, aneurysms, pseudoaneurysms, hematomas, infection, ischemic neuropathy, exacerbation of preexisting congestive heart failure, and stenosis. [ABSTRACT FROM AUTHOR]

Demand response is being actively considered as a useful mechanism for balancing supply and demand in the future power network. Relevant research to date has paid little attention to the interaction of this mechanism with the dynamics of the power network, focusing mainly on solving an appropriately formulated optimization problem. However, the coupling between the two should not be ignored due to fluctuations resulting from increased distributed energy resources and variability in both supply and demand. In this paper, we present a distributed control architecture that implements real-time economic optimization for the power network under exogenous disturbances. In particular, we consider a transmission level network with tree topology. Motivated by optimization decomposition methods, we first formulate a constrained Optimal Power Flow (OPF) problem and then use a primal–dual decomposition approach to design a dynamic feedback controller. We prove the asymptotic stability of the equilibria of the overall system. Numerical investigations illustrate that the proposed controller balances power flow in the network quickly, and achieves OPF in the steady state, even in the face of disturbances and contingencies. [ABSTRACT FROM AUTHOR]

The vast majority of new prostate cancer diagnoses are low-grade tumors that are monitored by active surveillance rather than undergoing immediate treatment. However, a subset of men will progress to advanced prostate cancer which may result in lethality, and these men are likely to benefit from early intervention to prevent or delay such progression. For this high-risk group, which includes aged men, men of African descent, and those with a hereditary predisposition to prostate cancer, informed risk stratification can be the cornerstone of clinical decision making and treatment intervention. In this review, we discuss the importance of a precision intervention approach that considers the cumulative risk for a given patient or population to develop prostate cancer or to progress to lethal disease, with particular focus on the interplay of major determinants of high-risk disease. • Age, race, oxidative stress and inflammation influence prostate cancer risk. • Genetic factors play a pivotal role in predicting prostate cancer onset and outcome. • Nuclear and mitochondrial genetic alterations point to prostate cancer susceptibility. • Integrative risk assessment may improve precision prostate cancer intervention. [ABSTRACT FROM AUTHOR]

Biochemical reaction networks tend to exhibit behaviour on more than one timescale and they are inevitably modelled by stiff systems of ordinary differential equations. Singular perturbation is a well-established method for approximating stiff systems at a given timescale. Standard applications of singular perturbation partition the state variable into fast and slow modules and assume a quasi-steady state behaviour in the fast module. In biochemical reaction networks, many reactants may take part in both fast and slow reactions; it is not necessarily the case that the reactants themselves are fast or slow. Transformations of the state space are often required in order to create fast and slow modules, which thus no longer model the original species concentrations. This paper introduces a layered decomposition, which is a natural choice when reaction speeds are separated in scale. The new framework ensures that model reduction can be carried out without seeking state space transformations, and that the effect of the fast dynamics on the slow timescale can be described directly in terms of the original species. [ABSTRACT FROM AUTHOR]

This paper draws on the results from a recent World Bank-funded project designed to inform policy-making and climate change adaptation planning in small and medium-sized cities in Latin America and the Caribbean. The focus was on floods and landslides, which are the two most common climate-related risks in cities across the region. The project allowed the application of the Urban Risk Assessment (URA) tool developed by the World Bank and the drawing of valuable lessons which may also be applicable to the many methods and tools available for climate change adaptation planning in the rapidly urbanising cities of developing countries. [ABSTRACT FROM AUTHOR]

The vast majority of new prostate cancer diagnoses are low-grade tumors that are monitored by active surveillance rather than undergoing immediate treatment. However, a subset of men will progress to advanced prostate cancer which may result in lethality, and these men are likely to benefit from early intervention to prevent or delay such progression. For this high-risk group, which includes aged men, men of African descent, and those with a hereditary predisposition to prostate cancer, informed risk stratification can be the cornerstone of clinical decision making and treatment intervention. In this review, we discuss the importance of a precision intervention approach that considers the cumulative risk for a given patient or population to develop prostate cancer or to progress to lethal disease, with particular focus on the interplay of major determinants of high-risk disease. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper, we develop algorithms for the computational analysis of stability and robust performance properties of nonlinear models governed by polynomial differential equations in quasi-Linear Parameter Varying form subject to parametric uncertainty. The methods presented use the sum of squares decomposition and ideas from real algebraic geometry to represent polynomial non-negativity over closed sets to compute various system properties such as [ABSTRACT FROM AUTHOR]

Abstract: This paper introduces a general framework for analysing nonlinear systems using absolute stability theory and sum of squares programming. The technique decomposes a vector field into a system with a polynomial vector field in feedback with a nonlinear memoryless term, which is contained in a generalised sector inequality with polynomial bounds. This decomposition can be used to model uncertainty in the nonlinearity or to bound difficult-to-analyse terms by simpler polynomial functions, such as time varying, non-polynomial or higher order nonlinearities. Conditions for stability and regions of attraction are found using polynomial and Lur’e type Lyapunov functions, which generalise those used for the derivation of the multivariable circle and Popov criteria in classical absolute stability. The technique extends both absolute stability theory and the applicability of sum of squares programming. The usefulness of the technique is demonstrated with illustrative examples. [Copyright &y& Elsevier]

Abstract: We investigate frequency synchronization and phase agreement in networks of non-identical Kuramoto oscillators with delayed coupling. We provide delay-dependent lower bounds for the coupling gain so that a network with all-to-all coupling and constant heterogeneous delays achieves synchronization. The given bounds are determined explicitly by the system parameters. Furthermore, we show that frequency synchronization and phase agreement are possible in general directed networks of non-identical oscillators which contain a spanning tree if the delays satisfy a self-consistency condition. Networks with delays differ at this point notably from networks without delays, because phase agreement is not possible in undelayed non-identical Kuramoto oscillator networks. In addition to the sufficient conditions for synchronization, we investigate the connection between phase agreement and the existence of solutions of a necessary self-consistency condition. [Copyright &y& Elsevier]

Abstract: Biological systems are typically modelled by nonlinear differential equations. In an effort to produce high fidelity representations of the underlying phenomena, these models are usually of high dimension and involve multiple temporal and spatial scales. However, this complexity and associated stiffness makes numerical simulation difficult and mathematical analysis impossible. In order to understand the functionality of these systems, these models are usually approximated by lower dimensional descriptions. These can be analysed and simulated more easily, and the reduced description also simplifies the parameter space of the model. This model reduction inevitably introduces error: the accuracy of the conclusions one makes about the system, based on reduced models, depends heavily on the error introduced in the reduction process. In this paper we propose a method to calculate the error associated with a model reduction algorithm, using ideas from dynamical systems. We first define an error system, whose output is the error between observables of the original and reduced systems. We then use convex optimisation techniques in order to find approximations to the error as a function of the initial conditions. In particular, we use the Sum of Squares decomposition of polynomials in order to compute an upper bound on the worst-case error between the original and reduced systems. We give biological examples to illustrate the theory, which leads us to a discussion about how these techniques can be used to model-reduce large, structured models typical of systems biology. [Copyright &y& Elsevier]

Bacteria are capable of sensing and responding to changes in their environment. One of the ways they do this is via chemotaxis, regulating swimming behaviour. The chemotaxis pathway senses chemoattractant gradients and uses a feedback loop to change the bacterial swimming pattern; this feedback loop differs in detail between species. In the present article, we summarize the current understanding of the regulatory mechanisms in three species and how these pathways can be viewed and analysed through the ideas of feedback control systems engineering. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated wet charred wood excavated at an archaic cemetery in Corfu, Greece, dating from 6th century B.C. The preservation condition of the material was evaluated based on its physicochemical properties and micromorphology in comparison to modern combusted wood. Charring temperature of the material was estimated by Electron Spin Resonance (ESR). Results indicated a severe degree of decay, resulting not only from charring. Conservation treatments involved spraying, as the material readily collapsed during immersion. Aqueous solutions of polyethylene glycol (PEG) were applied, as solvent soluble materials were found to be unsuitable due to the solvent’s volatility. Results showed that treatment efficacy was dependant on the moisture content of the material. Wet charred wood cannot be handled or treated like other wet or waterlogged organic materials. Further investigation is required to identify those properties which best characterize its preservation state and to assess the effectiveness of a wider range of conservation treatments. [Copyright &y& Elsevier]

Abstract: Energy-dispersive X-ray fluorescence spectroscopy was used to characterize red-slipped pottery (2nd–1st century BC) from ancient Cassope, north-western Greece. The compositional data were statistically treated by principal component analysis and chemical groups were established, representing locally produced and imported items. Mineralogical investigation by X-ray diffraction indicated firing temperatures in the range from 850 to 1000°C for most of the sherds, while one group consisted of over-fired items, possibly in excess of 1050°C. The morphology and elemental composition of the ceramic bodies and surface slips were examined through scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. The analyses revealed that different pottery groups exhibit surface slips of different nature, in terms of thickness, degree of vitrification and elemental composition. Overall, the diversity in technological characteristics of the examined sherds is indicative of the socio-economic conditions prevailing in Cassopaea during the late Hellenistic period. [Copyright &y& Elsevier]

Abstract: A highly ordered two-dimensional hybrid magnetic nanocomposite has been prepared by synthesizing and intercalating a new cationic aluminum-hydroxy ferric ferrocyanide compound into a cation-adsorbing nanoclay (montmorillonite). Chemical and structural properties were investigated by X-ray diffraction, transmission electron microscopy, thermogravimetric and differential thermal analyses, Fourier transform infrared, X-ray photoemission, and Mössbauer spectroscopies. Elemental analysis was based on proton-induced gamma ray emission and X-ray fluorescence spectroscopy data, N/C elemental ratios, and cation-exchange capacity measurements. Magnetic properties were studied by SQUID magnetometry. The results suggest: (i) that the cationic Prussian blue analog comprises Al-hydroxy cations embedded into a monolayer thick two-dimensional ferric ferrocyanide array; and (ii) that the clay-Prussian blue nanohybrid consists of such arrays stacked between the clay layers. The latter material orders ferromagnetically at ∼5K showing a hundred times higher remanence than that of the starting material, soluble Prussian blue (ammonium ferric ferrocyanide). [Copyright &y& Elsevier]

Abstract: Measurements of indoor radon levels and gamma dose rates were performed in 42 workplaces in Ioannina, north-western Greece. Radon concentrations followed a log-normal distribution with an arithmetic mean of 95±51Bqm−3. In all cases, radon levels were below 400Bqm−3, which is the action level implemented by the Greek Regulation for Radiation Protection, in accordance with the European Commission recommendation. Comparing summer and winter measurements, no statistically significant seasonal variation was established. However, radon concentrations measured in basement and ground floor workplaces were significantly higher (p <0.01) than those measured in the first and upper floors. Annual effective dose rates from inhalation of radon and its decay products were estimated to be in the range from 0.13 to 1.36mSvy−1 with a mean value of 0.62mSvy−1. Indoor exposure to natural gamma radiation entailed an average effective dose rate of 0.13mSvy−1, of which approximately 62% was due to terrestrial and the rest due to cosmic sources. The reported data contribute to the assessment of radon distribution and dose estimate at the national level. [Copyright &y& Elsevier]

Abstract: We investigate the robustness of consensus schemes for linear Multi-Agent Systems (MAS) to feedback delays. To achieve this, we develop a unified framework that considers linear MAS models with different feedback delays, e.g. affecting only the neighbor’s output, or affecting both the agent’s own and its neighbors’ output. This framework has the advantage of providing scalable, simple, and accurate set-valued conditions for consensus. Using these set-valued conditions, previous results on consensus in MAS with delays can be recovered and generalized. Moreover, we use them to derive conditions for the convergence rate of single integrator MAS with feedback delays. Finally, building on this framework, we propose a scalable delay-dependent design algorithm for consensus controllers for a large class of linear MAS. [ABSTRACT FROM AUTHOR]

AbstractWe describe a novel method to establish a prioriwhether the parameters of a nonlinear dynamical system are identifiable—that is, whether they can be deduced from output data (experimental observations). This is an important question as usually identifiability is assumed, and parameters are sought without first establishing whether these can be inferred from a set of measurements. We highlight the connections between parameter identifiability and state observability. We show how observability criteria can be used to check for identifiability, and we use new, state of the art computational tools to implement our approach. Nonlinear dynamical systems are prevalent in systems biology, where they are often used to represent a biological system. Thus, examples from biology are used to illustrate our method. [ABSTRACT FROM AUTHOR]

An important task for multi-agent systems (MAS) is to reach a consensus, e.g. to align their velocity vectors. Recent results propose appropriate consensus protocols to achieve such tasks, but most of them do not consider the effect of communication constraints such as the presence of time-delays in the exchange of information between the agents. In this article, we provide conditions for a non-linear, locally passive MAS of arbitrary size to reach a consensus, when the agents communicate over a packet-switched network that is characterised by a given topology. Both the cases of constant and switching topologies are considered. The nature of the communication channel imposes constraints that are modelled using stochastic delays of arbitrary distribution. We first embed this model in another, distributed but deterministic delay model and provide conditions for the error introduced by this simplification. In our main result, we provide conditions for the locally passive MAS with distributed delays to reach a consensus. In the case of a fixed topology, the underlying directed graph has to contain a spanning tree. In the case of a switching topology, only the union graph of all graphs that persist over time is required to contain a spanning tree. These conditions are independent of the distribution and the size of the packet delays. To show attractivity of the consensus set, we use an invariance principle for systems described by functional differential equations based on an appropriate Lyapunov-Razumikhin function. This methodological approach is the main contribution of this work and can also be applied to other consensus problems with delays. We illustrate our results by numerical simulations showing synchronisation of non-linear Kuramoto oscillators over a digital network. [ABSTRACT FROM AUTHOR]

Background: Determining the interaction topology of biological systems is a topic that currently attracts significant research interest. Typical models for such systems take the form of differential equations that involve polynomial and rational functions. Such nonlinear models make the problem of determining the connectivity of biochemical networks from time-series experimental data much harder. The use of linear dynamics and linearization techniques that have been proposed in the past can circumvent this, but the general problem of developing efficient algorithms for models that provide more accurate system descriptions remains open. Results: We present a network determination algorithm that can treat model descriptions with polynomial and rational functions and which does not make use of linearization. For this purpose, we make use of the observation that biochemical networks are in general 'sparse' and minimize the 1-norm of the decision variables (sum of weighted network connections) while constraints keep the error between data and the network dynamics small. The emphasis of our methodology is on determining the interconnection topology rather than the specific reaction constants and it takes into account the necessary properties that a chemical reaction network should have - something that techniques based on linearization can not. The problem can be formulated as a Linear Program, a convex optimization problem, for which efficient algorithms are available that can treat large data sets efficiently and uncertainties in data or model parameters. Conclusion: The presented methodology is able to predict with accuracy and efficiency the connectivity structure of a chemical reaction network with mass action kinetics and of a gene regulatory network from simulation data even if the dynamics of these systems are non-polynomial (rational) and uncertainties in the data are taken into account. It also produces a network structure that can explain the real experimental data of L. lactis and is similar to the one found in the literature. Numerical methods based on Linear Programming can therefore help determine efficiently the network structure of biological systems from large data sets. The overall objective of this work is to provide methods to increase our understanding of complex biochemical systems, particularly through their interconnection and their non-equilibrium behavior. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of this study was to determinate the accuracy of multidetector computed tomography (MDCT) angiography for imaging evaluation of renal anatomic variants among potential living renal donors for surgical planning. Materials and Methods: Two hundred twenty-three living kidney donors underwent MDCT angiography (MDCTA) in our institution over the last 2 years. The examination was performed with a 4-detector scanner, including scanning before and after power injection of nonionic contrast material during the arterial, nephrographic, and excretory phases. Scans were reconstructed for three-dimensional (3D) images using MIP, MPR, VRT, and CPR techniques. Results: Arterial variants, including supernumerary renal arteries, were present in 140 subjects: 11 presented luminal stenosis; 10 had calcifications within the vessel wall; 3 had renal artery aneurysms; 2 had obstructions; and 1 had angulation of the renal artery. Calcifications were associated with luminal stenosis (4 subjects) or no pathology (6 subjects). Venous variants were present in 4 subjects, including 3 retroaortic renal veins and 1 left renal vein draining into the retrohepatic portion of the IVC. Incidental findings were 3 renal infarcts. Conclusion: MDCTA and urography are a minimally invasive, fast method to detect and classify a variety of anatomic anomalies among potential living renal donors relevant to surgical planning. [Copyright &y& Elsevier]

Abstract: The thickness of a CR-39 detector is determined using an energy dispersive X-ray fluorescence (EDXRF) method of analysis. The method is based on exciting a suitable target and measuring the intensity of its fluorescence X-ray lines passing through the CR-39 sample in a fixed geometry. By properly selecting the target material, the method succeeds in assessing the thickness change of CR-39 detectors etched for different time intervals. The bulk etch rate (V b) may thus be obtained, which is an important parameter for any solid state nuclear track detector. Application of the EDXRF method yielded a value of V b =(2.01±0.04) μmh−1 for etching in a 6N NaOH solution at 75°C. This value agrees with the bulk etch rate of (1.90±0.03) μmh−1, obtained by the conventional mass-change method. [Copyright &y& Elsevier]

Abstract: Energy-dispersive X-ray fluorescence spectroscopy was used to determine the composition of 64 potsherds from the Hellenistic settlement of Orraon, in northwestern Greece. Data classification by principal components analysis revealed four distinct groups of pottery, pointing to different local production practices rather than different provenance. The interpretation of statistical grouping was corroborated by a complementary X-ray diffraction analysis. Compositional and mineralogical data, combined with archaeological and materials’ science criteria, allowed addressing various aspects of pottery making, such as selection of raw clays, tempers and firing conditions. [Copyright &y& Elsevier]

The profile of soil gas radon was monitored in five active fault sites in northern and northwestern Greece. Measurements were carried out during summer months, using CR-39 solid state nuclear track detectors (SSNTDs). The spatial distribution of radon along lines traversing the fault zones revealed anomalies, clearly connected to the local tectonic structure. Specifically, increased radon signals evolved on the radon background level, in the vicinity of the faults’ axes and the signal-to-background ratio ranged from 2 to 13. The consistency of this pattern confirms that the radon technique is powerful in the detection and mapping of active fault zones. [Copyright &y& Elsevier]

Gamma-ray spectrometry was used to determine uranium activity and investigate the presence of depleted uranium in soil samples collected from camping sites of the Greek expeditionary force in Kosovo. Assessment of 238U concentrations was based on measurements of the 63.3 keV and 92.38 keV emissions of its first daughter nuclide, 234Th. To determine the isotopic ratio of 238U/235U, secular equilibrium along the two radioactive series was first ensured and thereby the contribution of 235U under the 186 keV peak was deduced. The uranium activity in the samples varied from 48 to 112 Bq kg−1, whereas the activity ratio of 238U/235U averaged 23.1±4.3. [Copyright &y& Elsevier]

Strontium adsorption was studied in an aluminum-pillared montmorillonite (PILC) carrying organic acid groups. The in situ dissociation of these groups increases the number of negative sites in the modified PILC, promoting thus the uptake of cations from an exchange solution. To investigate the role of solution pH and acid strength in cation uptake phenomena, base titrations were performed for PILCs carrying either oxalate or acetate groups. Comparison with the pristine PILC showed that extra Sr2+ uptake initiated at pH 6 and 8 in the presence of oxalate and acetate, respectively. The overall increase in Sr2+ uptake was higher in the presence of oxalate and amounted to about 136% as compared with the pristine PILC, at pH slightly above 8. The effect of the acid''s strength was further probed through strontium adsorption isotherms, taken at a constant pH for PILC samples carrying acetate, oxalate, malonate, or citrate groups. The results demonstrate that cation uptake can be optimized by tuning the pH conditions to the acid''s strength or vice versa. [Copyright &y& Elsevier]

ABO3 perovskites offer versatile photoactive nano-templates that can be optimized towards specific technologies, either by means of doping or via heterojunction engineering. SrTiO3 is a well-studied perovskite photocatalyst, with a highly reducing conduction-band edge. Herein we present a Double-Nozzle Flame Spray Pyrolysis (DN-FSP) technology for the synthesis of high crystallinity SrTiO3 nanoparticles with controlled La-doping in tandem with SrTiO3/CuO-heterojunction formation. So-produced La:SrTiO3/CuO nanocatalysts were optimized for photocatalysis of H2O/CH3OH mixtures by varying the La-doping level in the range from 0.25 to 0.9%. We find that, in absence of CuO, the 0.9La:SrTiO3 material achieved maximal efficient photocatalytic H2 production, i.e., 12 mmol g−1 h−1. Introduction of CuO on La:SrTiO3 enhanced selective production of methane CH4. The optimized 0.25La:SrTiO3/0.5%CuO catalyst achieved photocatalytic CH4 production of 1.5 mmol g−1 h−1. Based on XRD, XRF, XPS, BET, and UV-Vis/DRS data, we discuss the photophysical basis of these trends and attribute them to the effect of La atoms in the SrTiO3 lattice regarding the H2-production, plus the effect of interfacial CuO on the promotion of CH4 production. Technology-wise this work is among the first to exemplify the potential of DN-FSP for scalable production of complex nanomaterials such as La:SrTiO3/CuO with a diligent control of doping and heterojunction in a single-step synthesis. [ABSTRACT FROM AUTHOR]