Importance There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS). Objective To determine how serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression. Design, Setting, and Participants Data were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022. The SMSC is a prospective, multicenter study performed in 8 centers in Switzerland. For this nested study, participants had to meet the following inclusion criteria: cohort 1, patients with MS and either stable or worsening disability and similar baseline Expanded Disability Status Scale scores with no relapses during the entire follow-up; and cohort 2, all SMSC study patients who had initiated and continued B-cell-depleting treatment (ie, ocrelizumab or rituximab). Exposures Patients received standard immunotherapies or were untreated. Main Outcomes and Measures In cohort 1, sGFAP and sNfL levels were measured longitudinally using Simoa assays. Healthy control samples served as the reference. In cohort 2, sGFAP and sNfL levels were determined cross-sectionally. Results This study included a total of 355 patients (103 [29.0%] in cohort 1: median [IQR] age, 42.1 [33.2-47.6] years; 73 female patients [70.9%]; and 252 [71.0%] in cohort 2: median [IQR] age, 44.3 [33.3-54.7] years; 156 female patients [61.9%]) and 259 healthy controls with a median [IQR] age of 44.3 [36.3-52.3] years and 177 female individuals (68.3%). sGFAP levels in controls increased as a function of age (1.5% per year; P < .001), were inversely correlated with BMI (-1.1% per BMI unit; P = .01), and were 14.9% higher in women than in men (P = .004). In cohort 1, patients with worsening progressive MS showed 50.9% higher sGFAP levels compared with those with stable MS after additional sNfL adjustment, whereas the 25% increase of sNfL disappeared after additional sGFAP adjustment. Higher sGFAP at baseline was associated with accelerated gray matter brain volume loss (per doubling: 0.24% per year; P < .001) but not white matter loss. sGFAP levels remained unchanged during disease exacerbations vs remission phases. In cohort 2, median (IQR) sGFAP z scores were higher in patients developing future confirmed disability worsening compared with those with stable disability (1.94 [0.36-2.23] vs 0.71 [-0.13 to 1.73]; P = .002); this was not significant for sNfL. However, the combined elevation of z scores of both biomarkers resulted in a 4- to 5-fold increased risk of confirmed disability worsening (hazard ratio [HR], 4.09; 95% CI, 2.04-8.18; P < .001) and PIRA (HR, 4.71; 95% CI, 2.05-9.77; P < .001). Conclusions and Relevance Results of this cohort study suggest that sGFAP is a prognostic biomarker for future PIRA and revealed its complementary potential next to sNfL. sGFAP may serve as a useful biomarker for disease progression in MS in individual patient management and drug development.

Dynamic covalent chemistry (DCC) has proven to be a valuable tool in creating fascinating molecules, structures, and emergent properties in fully synthetic systems. Here we report a system that uses two dynamic covalent bonds in tandem, namely disulfides and hydrazones, for the formation of hydrogels containing biologically relevant ligands. The reversibility of disulfide bonds allows fiber formation upon oxidation of dithiol-peptide building block, while the reaction between NH-NH2 functionalized C-terminus and aldehyde cross-linkers results in a gel. The same bond-forming reaction was exploited for the "decoration" of the supramolecular assemblies by cell-adhesion-promoting sequences (RGD and LDV). Fast triggered gelation, cytocompatibility and ability to "on-demand" chemically customize fibrillar scaffold offer potential for applying these systems as a bioactive platform for cell culture and tissue engineering.

Portal vein aneurysm (PVA) is a rare vascular abnormality, representing 3% of all venous aneurysms in the human body, and is not well understood. It can be congenital or acquired, located mainly at the level of confluence, main trunk, branches and bifurcation. A PVA as an abnormality of the portal venous system was first reported in 1956 by Barzilai and Kleckner. A review from 2015 entitled “Portal vein aneurysm: What to know” considered fewer than 200 cases. In the last seven years, there has been an increase in the number of PVAs diagnosed thanks to routine abdominal imaging. The aim of this review is to provide a comprehensive update of PVA, including aetiology, epidemiology, and clinical assessment, along with an evaluation of advanced multimodal imaging features of aneurysm and management approaches.

Background: Possible solutions to overcome the many challenges of home delivery are collection and delivery points (CDPs). In addition to commercial facilities, the role of CDPs can also be played by users’ households, providing a crowd storage service. Key decisions regarding CDPs relate to their location, as well as the allocation of users to selected locations, so that the distance of users from CDPs is minimal. Methods: In this paper, the described problem is defined as a p-median problem and solved for the area of the city of Belgrade, using the heuristic “greedy” and the simulated annealing algorithm. Results: Fifty locations of CDPs were selected and the users allocated to them were distributed in over 950 zones. The individual distances between users and the nearest CDPs and the sum of these distances, multiplied by the number of requests, were obtained. An example of modification of the number of CDPs is presented as a way of obtaining solutions that correspond to different preferences of operators and/or users in terms of their distances from the CDPs. Conclusions: User households can be used as CDPs to achieve various benefits. Locating CDPs, i.e., selecting households, can be solved as a p-median problem, using a combination of heuristic and metaheuristic algorithms. In addition, by modifying the number of medians, the total and average distances between users and CDPs can be better managed. The main contributions of the paper are the establishment of users’ households as potential locations of CDPs, the establishment of a framework for analysis of impact of the number of CDPs on the sum and average distances from the customers, as well as the creation of a basis for upgrading and modifying the model for implementation in the business practice.

Abstract Excavations of the Kopilo cemetery in central Bosnia in 2021 and 2022 have provided the first insights into Bronze and Iron Age burial practices in this part of Europe. We documented a total of 46 inhumation graves, with the variety of finds indicating supra-regional contacts of this population.

It is a continuous imperative to establish the most efficient process of conversion of primary energy from fuel through combustion, which also has the least possible harmful effect on the environment. In this time of expressed demands for decarbonisation, it also means the affirmation of the use of renewable fuels and the indispensable application of appropriate primary measures in the combustion furnace. At the same time, the efficiency of the combustion process depends on several factors, from the type and properties of the fuel to the ambient and technological settings for the process. In this regard, with the aim of determining the static characteristics of combustion, experimental laboratory research was carried out on the combustion of mixtures of brown coal with low heating value and a high ash content with waste woody biomass and different process conditions: temperature, staged combustion air supply (air staging) and in conditions of application of a third or additional fuel (natural gas, reburning technology). Applied experimental methods included the analysis of the combustion process on the basis of input (reactants) - output (products), including the analysis of the composition of flue gases, i.e. the determination of the emission of the key components of flue gases CO2, CO, NOx and SO2, as well as the analysis of the composition of slag, ash and deposits ash, i.e. assessment and evaluation of the behaviour of ash from fuel in that process. Based on the obtained research results, this paper shows the significant positive effects of the application of primary measures in the furnace - compared to conventional combustion: air staging - reduction of net CO2 emissions during co-firing with biomass and reduction of NOx emissions by up to 30%; reburning technology - additional reduction of CO2 and NOx emissions in proportion to the share of natural gas, e.g. at a combustion process temperature of 1350 °C and at a 10% energy share of natural gas during the co-firing of a mixture of brown coal and waste woody biomass, compared to the emission without the use of natural gas, a reduction of NOx emissions by 185 mg/mn3 or by almost 30% was recorded. It was concluded, at the same time, the application of these primary measures in the furnace does not negatively affect the behaviour of ash from the fuel in the given settings of the combustion process.

The floor and ceiling functions appear often in mathematics and manipulating sums involving floors and ceilings is a subtle game. Fortunately, the well-known textbook Concrete Mathematics provides a nice introduction with a number of techniques explained and a number of single or double sums treated as exercises. For two such double sums we provide their single-sum analogues. These closed-form identities are given in terms of a dual partition of the multiset (regarded as a partition) of all b-ary digits of a nonnegative integer. We also present the double- and single-sum analogues involving the fractional part function and the shifted fractional part function.

Introduction: Physical activity has a positive effect on the regulation of diabetes mellitus and has been shown to have benefits in improving health. Aim: Examine the effects of physical activity on changes in glycemic parameters (glucose, HbA1C) and inflammatory parameters (leukocyte count (WBC), CRP) before and one month after the exercise program. Material and Methods: The study was designed as a prospective, analytical, and observational study. Results: T-test of paired samples assessed the impact of physical activity on glycemic and inflammatory parameters in subjects with confirmed Diabetes mellitus type 2 and in subjects without confirmed diabetes mellitus type 2. In subjects with confirmed diabetes the value of eta squared (ɳ2 - eta sqared) is 95%, which indicates a significant impact of physical activity on the change in glucose values and on the change of HbA1C value was indicated by the value of eta square of 93%. When it comes to inflammatory parameters, the impact of physical activity was found in the reduced number of WBC (ɳ2 = 88%), and in CRP (ɳ2 = 90%). In subjects without confirmed diabetes mellitus, a significant effect of physical activity on the change in glucose (ɳ2 = 94%) and HbA1C (ɳ2 = 77%). The influence of physical activity on the reduction of leukocyte count was proven by ɳ2 - eta sqared test (ɳ2 = 66%), as well as a decrease in CRP (ɳ2 = 30%). Conclusion: This study showed a significant impact of physical activity on the reduction of elevated glycemic and inflammatory parameters.

Since August 2022 customers have to be asked if they are interested in sustainable investment when entering a pension contract. Hence, the provider has to be prepared to offer suitable investment opportunities. Further, the provider has to manage the new risks and chances of those assets in the whole portfolio. We therefore especially look at possible consequences for optimal portfolio decisions of a life insurer and suggest modeling approaches for the evolution of the demand and the sustainability ratings for sustainable assets. We will solve various portfolio problems under sustainability constraints explicitly and suggest further research topics. As a special feature for a life insurer, we particularly look at the role of the actuarial reserve fund and the annual declaration of its return.

Waste disposal is just one of the segments in solid municipal waste management system. During the entire life cycle of waste, starting from waste generation, through storage, collection, transport, recycling, treatment and disposal, several different pollutants are emitted. By disposing solid waste, non-road mobile machinery (NRMM) emits various pollutants into the air such as CO2, CO, NMVOC, PM, PAHs, heavy metals, etc. These substances can pose certain problems for human health and the environment. The subject of this study is the calculation of air emissions of CO2, CH4, N2O, NMVOC, PM10, CO, Cd, Cr and PAHs (chrysene and benz[a]anthracene) from NRMM which are included in the activities of receiving and disposing of waste at the Banja Luka landfill. The study evaluates the emission of pollutants using the EEA guidelines for the assessment of the emission of pollutants into the air, based on the consumption of diesel fuel during the year. This study, which is based on the calculation of NRMM emissions at the Banja Luka landfill, should serve as an example not only to other landfills but also to sectors that use NRMM on the importance of keeping track of pollutant emissions. The goal is to look at these emissions and introduce changes and improvements in this sector by replacing old NRMMs with new ones, optimizing operation, using diesel of satisfactory quality, etc.

The municipal solid waste (MSW) landfill is recognized as an anthropogenic source of air pollutants that can have a negative impact on human health and the environment. Workers who work at the MSW landfill may be exposed to risk due to the inhalation of substances such as volatile organic compounds (VOCs). Although VOCs account for 1% in landfill gas, they are important because of the high level of toxicity associated with them. Regular monitoring of air quality and risk assessment provides important information in protecting the health of workers at the landfill. This study focuses on a health risk assessment related to VOCs (benzene, toluene and xylene) exposure via inhalation for workers at a landfill Banja Luka, Republic of Srpska, Bosnia and Herzegovina. Additionally, cancer risk and non-cancer risk of benzene, toluene and xylene of workers indicated that occupational exposures were above recommended standard. This implies that landfill workers are exposed to a significant health risk associated with inhalation exposure to VOCs

We design and demonstrate a method for early detection of Denial-of-Service attacks. The proposed approach takes advantage of the OpenRAN framework to collect measurements from the air interface (for attack detection) and to dynamically control the operation of the Radio Access Network (RAN). For that purpose, we developed our near-Real Time (RT) RAN Intelligent Controller (RIC) interface. We apply and analyze a wide range of Machine Learning algorithms to data traffic analysis that satisfy the accuracy and latency requirements set by the near-RT RIC. Our results show that the proposed framework is able to correctly classify genuine vs. malicious traffic with high accuracy (i.e., 95%) in a realistic testbed environment, allowing us to detect attacks already at the Distributed Unit (DU), before malicious traffic even enters the Centralized Unit (CU).

Background: Outcomes after acute rheumatic fever (ARF) diagnosis are variable, ranging from recovery to development of severe rheumatic heart disease (RHD). There is no diagnostic test. Evaluation using the Australian clinical diagnostic criteria can result in a diagnosis of definite, probable or possible ARF. The possible category was introduced in 2013 in Australias Northern Territory (NT). Our aim was to compare longitudinal outcomes after a diagnosis of definite, probable or possible ARF. Methods: We extracted data from the NT RHD register for Indigenous Australians with an initial diagnosis of ARF during the 5.5-year study period (01/01/2013 - 30/06/2019). Descriptive statistics were used to describe the demographic and clinical characteristics at initial ARF diagnosis. Kaplan-Meier curves were used to assess the probability of survival free of disease progression and the cumulative incidence risk at each year since initial diagnosis was calculated. Cox proportional hazards regression was used to determine whether time to disease progression differed according to ARF diagnosis and whether progression was associated with specific predictors at diagnosis. A multinomial logistic regression model was performed to assess whether ARF diagnosis was associated with RHD outcome and to assess associations between ARF diagnosis and clinical manifestations. A generalised linear mixed model (GLMM) was developed to assess any differences in the long-term antibiotic adherence between ARF diagnosis categories and to examine longitudinal trends in adherence. Results: There were 913 initial ARF cases, 732 with normal baseline echocardiography. Of these, 92 (13%) experienced disease progression: definite ARF 61/348 (18%); probable ARF 20/181 (11%); possible ARF 11/203 (5%). The proportion of ARF diagnoses that were uncertain (i.e. possible or probable) increased over time, from 22/78 (28%) in 2013 to 98/193 (51%) in 2018. Cumulative incidence risk of any disease progression at 5.5 years was 33.6 (23.6-46.2) for definite ARF, 13.5 (8.8-20.6) for probable and 11.4% (95% CI 6.0-21.3) for possible ARF. The probability of disease-free survival was lowest for definite ARF and highest for possible ARF (p=0.004). Cox proportional hazards regression indicated that disease progression was 2.19 times more likely in those with definite ARF than those with possible ARF (p=0.026). Progression to RHD was reported in 37/348 (11%) definite ARF, 10/181 (6%) probable ARF, and 5/203 (2%) possible ARF. The multinomial logistic regression model demonstrated a significantly higher risk of progression from no RHD to RHD if the initial diagnosis was definite compared to possible ARF (p<0.001 for both mild and moderate-severe RHD outcomes). The GLMM estimated that patients with definite ARF had a significantly higher adherence to antibiotic prophylaxis compared with probable ARF (p=0.024). Conclusion: These data indicate that the ARF diagnostic categories are being applied appropriately, are capturing more uncertain cases over time, provide a useful way to stratify risk and guide prognosis, and can help inform practice. Possible ARF is not entirely benign; some cases progress to RHD.

2D materials have attracted broad attention from researchers for their unique electronic properties, which may be been further enhanced by combining 2D layers into vertically stacked van der Waals heterostructures (vdWHs). Among the superlative properties of 2D systems, thermoelectric (TE) energy conversion promises to enable targeted energy conversion, localized thermal management, and thermal sensing. However, TE conversion efficiency remains limited by the inherent tradeoff between conductivity and thermopower. In this paper, we use first-principles calculation to study graphene-based vdWHs composed of graphene layers and hexagonal boron nitride (h-BN). We compute the electronic band structures of heterostructured systems using Quantum Espresso and their TE properties using BoltzTrap2. Our results have shown that stacking layers of these 2D materials opens a bandgap, increasing it with the number of h-BN interlayers, which significantly improves the power factor (PF). We predict a PF of ∼1.0 × 1011 W K−2 m s for the vdWHs, nearly double compared to 5 × 1010 W K−2 m s that we obtained for single-layer graphene. This study gives important information on the effect of stacking layers of 2D materials and points toward new avenues to optimize the TE properties of vdWHs.