Detailed characterization of medullary and extramedullary reservoirs of osteoclast progenitors (OCPs) is required to understand the pathophysiology of increased periarticular and systemic bone resorption in arthritis. In this study, we focused on identifying the OCP population specifically induced by arthritis and the role of circulatory OCPs in inflammatory bone loss. In addition, we determined the relevant chemokine axis responsible for their migration, and targeted the attraction signal to reduce bone resorption in murine collagen-induced arthritis (CIA). OCPs were expanded in periarticular as well as circulatory compartment of arthritic mice, particularly the CCR2hi subset. This subset demonstrated enhanced osteoclastogenic activity in arthritis, whereas its migratory potential was susceptible to CCR2 blockade in vitro. Intravascular compartment of the periarticular area contained increased frequency of OCPs with the ability to home to the arthritic bone, as demonstrated in vivo by intravascular staining and adoptive transfer of splenic LysMcre/Ai9 tdTomato-expressing cells. Simultaneously, CCL2 levels were increased locally and systemically in arthritic mice. Mouse cohorts were treated with the small-molecule inhibitor (SMI) of CCR2 alone or in combination with methotrexate (MTX). Preventive CCR2/CCL2 axis blockade in vivo reduced bone resorption and OCP frequency, whereas combining with MTX treatment also decreased disease clinical score, number of active osteoclasts, and OCP differentiation potential. In conclusion, our study characterized the functional properties of two distinct OCP subsets in CIA, based on their CCR2 expression levels, implying that the CCR2hi circulatory-like subset is specifically induced by arthritis. Signaling through the CCL2/CCR2 axis contributes to OCP homing in the inflamed joints and to their increased osteoclastogenic potential. Therefore, addition of CCL2/CCR2 blockade early in the course of arthritis is a promising approach to reduce bone pathology.

The aim of this international multicentre study was to review potential drug–drug interactions (DDIs) for real‐life coadministration of combination antiretroviral therapy (cART) and coronavirus disease 2019 (COVID‐19)‐specific medications.

Sustainable technologies are being increasingly used in various areas of human life. While they have a multitude of benefits, they are especially useful in health monitoring, especially for certain groups of people, such as the elderly. However, there are still several issues that need to be addressed before its use becomes widespread. This work aims to clarify the aspects that are of great importance for increasing the acceptance of the use of this type of technology in the elderly. In addition, we aim to clarify whether the technologies that are already available are able to ensure acceptable accuracy and whether they could replace some of the manual approaches that are currently being used. A two-week study with people 65 years of age and over was conducted to address the questions posed here, and the results were evaluated. It was demonstrated that simplicity of use and automatic functioning play a crucial role. It was also concluded that technology cannot yet completely replace traditional methods such as questionnaires in some areas. Although the technologies that were tested were classified as being “easy to use”, the elderly population in the current study indicated that they were not sure that they would use these technologies regularly in the long term because the added value is not always clear, among other issues. Therefore, awareness-raising must take place in parallel with the development of technologies and services.

Regular curriculum modifications and the shift from a teacher-centered to a learner-centered paradigm in educational institutions are meant to enhance the teaching-learning process and fulfill learners' needs as successfully as possible. This study aimed to examine learners' attitudes towards learning English, their needs/wants, learning preferences, strategies, and lesson topics. Moreover, it also investigated the differences in learning preferences based on grade level.  The data were gathered from a survey administrated to 200 elementary school students in Central Bosnia and Herzegovina. The findings illustrated that the participants generally have a positive attitude towards learning English with more significant extrinsic reasons motivating them to learn it. Regarding students' needs, the analysis revealed that overall, students found writing the most challenging and speaking the most desirable language skill. Furthermore, the majority of the participants reported that they like to learn by reading texts or stories, finding the discussion in the classroom the most annoying classroom activity. While learning vocabulary by translating new words is regarded as the most beneficial method, doing written exercises at school presents the most significant way of acquiring grammar. Moreover, the study identified a significant influence of a grade level on the preferred ways of learning English.

The objective of this study was to determine and compare the antimicrobial resistance profiles of clinical Staphylococcus pseudintermedius (n = 90) and Staphylococcus aureus (n = 61) isolates from different animal species in Bosnia and Herzegovina. Among S. pseudintermedius isolates from dogs (n = 86), resistance to penicillin (87.2%) was most common followed by amoxicillin (76.7%) and amoxicillin/clavulanic acid (67.4%). A total of 25 isolates were found to be resistant to oxacillin of which 21 were mecA-positive and multidrug resistant (MDR). The most frequent MDR pattern was penicillins-lincosamides-cephalosporins-macrolides-fluoroquinolones. Among the 61 methicillin-susceptible S. pseudintermedius isolates, 18 were MDR (penicillins-lincosamides-macrolides). Most of S. aureus isolates were resistant to penicillin (50.8%), followed by amoxicillin (41%) and amoxicillin/clavulanic acid (31%). Resistance to cefoxitin was detected in only two isolates. All S. aureus isolates were mecA and mecC-negative. MDR was observed in six S. aureus isolates of which five were from cattle (penicillins-lincosamides-fluoroquinolones). Isolates from red foxes (Vulpes vulpes) were sensitive to most of the antimicrobials tested. The high number of methicillin-resistant S. pseudintermedius and MDR isolates in dogs exposed in this study underlines the urgent need for establishment of national antimicrobial resistance surveillance program in animals in the country, as well as for the surveillance of veterinary antimicrobial consumption.

Recent years have seen a surge in popularity of concession projects, particularly in certain sectors such as energy, mining, and geological explorations. These projects are not only significant and beneficial for the investors, but they are also boosting local economies. The very foundation of such projects is the concession contract (CC)—contract with both public and private law elements determining the relations between the state organ issuing the concession and the private entity. This paper will focus on the case of Bosnia and Herzegovina (B&H) where CCs are often unbalanced and commonly unilaterally designed by the state party that dictates all of its provisions. Consequently, the private party is placed in a difficult, take-it-or-leave-it situation if it does not want to accept the CC as drafted by the state party. Potential steps toward the implementation of World Commerce & Contracting Principles (WCC Principles) in the CCs in B&H shall be presented, along with their predictable benefits and likely impact on the shortening and balancing the process of negotiating the CC in B&H.

Abstract The Balkan Peninsula and the Dinaric Mountains possess extraordinary biodiversity and support one of the largest and most diverse wolf (Canis lupus) populations in Europe. Results obtained with diverse genetic markers show west‐east substructure, also seen in various other species, despite the absence of obvious barriers to movement. However, the spatial extent of the genetic clusters remains unresolved, and our aim was to combine fine‐scale sampling with population and spatial genetic analyses to improve resolution of wolf genetic clusters. We analyzed 16 autosomal microsatellites from 255 wolves sampled in Slovenia, Croatia, Bosnia and Herzegovina (BIH), and Serbia and documented three genetic clusters. These comprised (1) Slovenia and the regions of Gorski kotar and Lika in Croatia, (2) the region of Dalmatia in southern Croatia and BIH, and (3) Serbia. When we mapped the clusters geographically, we observed west‐east genetic structure across the study area, together with some specific structure in BIH–Dalmatia. We observed that cluster 1 had a smaller effective population size, consistent with earlier reports of population recovery since the 1980s. Our results provide foundation for future genomic studies that would further resolve the observed west‐east population structure and its evolutionary history in wolves and other taxa in the region and identify focal areas for habitat conservation. They also have immediate importance for conservation planning for the wolves in one of the most important parts of the species’ European range.

Brain parenchyma infiltration with glioblastoma (GB) cannot be entirely visualized by conventional magnetic resonance imaging (MRI). The aim of this study was to investigate changes in the energy and membrane metabolism measured with phosphorous MR spectroscopy (31P-MRS) in the presumably “normal-appearing” brain following chemoradiation therapy (CRT) in GB patients in comparison to healthy controls. Twenty (seven female, thirteen male) GB patients underwent a 31P-MRS scan prior to surgery (baseline) and after three months of standard CRT (follow-up examination. The regions of interest “contrast-enhancing (CE) tumor” (if present), “adjacent to the (former) tumor”, “ipsilateral distant” hemisphere, and “contralateral” hemisphere were compared, differentiating between patients with stable (SD) and progressive disease (PD). Metabolite ratios PCr/ATP, Pi/ATP, PCr/Pi, PME/PDE, PME/PCr, and PDE/ATP were investigated. In PD, energy and membrane metabolism in CE tumor areas have a tendency to “normalize” under therapy. In different “normal-appearing” brain areas of GB patients, the energy and membrane metabolism either “normalized” or were “disturbed”, in comparison to baseline or controls. Differences were also detected between patients with SD and PD. 31P-MRS might contribute as an additional imaging biomarker for outcome measurement, which remains to be investigated in a larger cohort.

Dual-task balance studies explore interference between balance and cognitive tasks. This study is a descriptive analysis of accelerometry balance metrics to determine if a verbal cognitive task influences postural control after the task ends. Fifty-two healthy older adults (75 ± 6 years old, 30 female) performed standing balance and cognitive dual-tasks. An accelerometer recorded movement from before, during, and after the task (reciting every other letter of the alphabet). Thirty-six balance metrics were calculated for each task condition. The effect of the cognitive task on postural control was determined by a generalized linear model. Twelve variables, including anterior–posterior centroid frequency, peak frequency and entropy rate, medial-later entropy rate and wavelet entropy, and bandwidth in all directions, exhibited significant differences between baseline and cognitive task periods, but not between baseline and post-task periods. These results indicate that the verbal cognitive task did alter balance, but did not bring about persistent effects after the task had ended. Traditional balance measurements, i.e., root mean square and normalized path length, notably lacked significance, highlighting the potential to use other accelerometer metrics for the early detection of balance problems. These novel insights into the temporal dynamics of dual-task balance support current dual-task paradigms to reduce fall risk in older adults.

Abstract Community mobility involves walking with physical and cognitive challenges. In older adults (N=116; results here from initial analyses: N=29, Age=75±5 years, 51% females), we assessed gait speed and smoothness (harmonic-ratio) while walking on even and uneven surfaces, with or without an alternate alphabeting dual-task (ABC). ANOVA assessed surface and dual-task effects; Pearson correlations compared gait with global cognition and executive function composite z-scores. The four conditions (even, uneven, even-ABC and uneven-ABC) affected speed(m/s) (0.97±0.14 vs 0.90±0.15 vs 0.83±0.17 vs 0.79±0.16). Smoothness (2.19±0.48 vs 1.89±0.38 vs 1.92±0.53 vs 1.7±0.43) was affected by only surface (controlled for speed). Greater speed was associated with better global cognition(ρ=0.47 to 0.49, p<0.05) for all conditions and with better executive function for even-ABC(ρ=0.39, p=0.04) and uneven-ABC(ρ=0.40, p=0.03). Executive function was associated with smoothness during even(ρp=-0.42, p=0.03) and uneven(ρp=-0.39, p=0.04) walking. Type of walking challenge differentially affects gait quality and associations with cognitive function.

Institute for Mathematics and Democracy The Institute for Mathematics and Democracy (IMD)1 was created to help cast light on the important role that mathematics plays in our political systems. Founded in 2019, it is housed at Wellesley College, a liberal arts institution with a strong interest in interdisciplinary work. The mission of IMD is to promote a deeper understanding of the mathematics that underlies many socioeconomic forces and political processes so that citizens can make informed political decisions and effect meaningful change. It supports research, teaching, and outreach in mathematics and democracy, and brings together educators and activists who recognize the importance of political quantitative literacy. It acts as a facilitator, a repository, and nexus to bring research and pedagogy of disparate individuals who synthesize mathematics and democracy in their research and teaching. The timeliness of these efforts is apparent as IMD is finding a wide and growing audience among students, researchers, educators, activists, and the public at large. Over thirty mathematicians now serve as scholars and affiliates for IMD, many of whom have pursued or supervised research, run summer programs, or created curricula at the intersection of politics and mathematics. The institute has also supported over twenty student researchers, almost half of them from underrepresented groups. The activities of IMD are rooted and motivated by mathematics, but they lie at the unique interdisciplinary interface of mathematics, statistics, political science, economics, and history. Not only do they fill an evident educational and research gap, but they serve a social purpose: political

In the Roman legal tradition, but also in modern civil law systems, the term commorientes (lat. commorientes) refers to persons who died in the same accident or other danger, standing in a legal position relevant to inheritance law. In connection with the resolution of such situations in the theory of private law, various legal presumptions have been developed since the period of classical Roman law. All these presumptions can be systematized within two basic concepts - the first based on the presumption of survival of subjects and the second based on the presumption of the simultaneous death of subjects. Comparatively, in the development of European private law, there has been a reception of both concepts, with the proviso that over time the concept of simultaneity will almost completely suppress the concept of survival. The paper analyzes the reasons for this. In establishing a link between Roman roots and European private law, special attention is given to the possibility of applying presumptions in cases where there is a certain spatial or temporal distance between the deaths of persons or if a different cause has led to fatal consequences. Ultimately, the paper clearly points to the importance of Roman rules, which can sometimes be fundamental in understanding the institutes of contemporary private law.

Abstract Background: Due to strong empirical evidence from different markets, existence of value premium became a financial theory standpoint. Although previous studies found that value stocks beat growth stocks in bearish and bullish markets, during the GFC, value stocks underperformed growth stocks. Objectives: This paper aims to examine the performance of value and growth stock portfolios after the GFC. Subjects of our analysis are constituent companies of the DJIA index, out of which portfolios of large-cap value and growth stocks have been constructed and evaluated. Methods/Approach: We measure the performance of stock portfolios, which are created based on the naïve diversification rule and random weighting approach. Statistical testing includes Levene’s homogeneity test, the Mann-Whitney U test, T-test, and the One-Sample T-test. Results: Growth stock portfolios outperform value stock portfolios after the GFC. The dominance of growth stock portfolios compared to value stock portfolios is significant, and the value premium disappears. Conclusions: Financial theory and investment management implications show that growth stocks have overtaken the dominance over value stocks since 2009. Causes might be in (1) expansionary monetary policy characterized by very low long-term interest rates and (2) high performance of the tech industry to which most growth stocks belong.

Background: Invasive ductal cancer (IDC) represents about 75% of all breast malignancies. There are many breast cancer prognostic factors, but the ones that have the most impact on the survival rates in advanced breast cancer are tumor size and regional lymph node involvement. Axillary lymph node dissection (ALND) has particularly important and undoubtful role in current surgical options for breast cancer treatment. With the introduction of sentinel lymph node biopsy (SLNB) for breast cancer patients it was possible to identify those to whom regional spread of the disease did not occur at the time of surgery, and thus spare them an unnecessary ALND procedure. Objective: To determine the rate of sentinel lymph node (SLN) detection using only methylene blue dye as a mapping agent, as well as to correlate the number of positive SLNs with the number of positive non-sentinel lymph nodes (non-SLNs). Methods: The study represents a prospective study that included 50 female patients with histologically confirmed invasive ductal carcinoma (IDC) who underwent SLNB using only methylene blue dye as the mapping agent, while the detection and harvest of SNL was done by visual control only. All patients also underwent an obligatory complete ALND, which was as that time the institutional oncological protocol for surgical treatment of histologically confirmed IDC. The final data such as tumor size, SLN and non-SLN status were obtained by further analysis of pathohistological reports from tumor biopsy and other surgical specimens. Results: The accuracy rate of SLN detection was 98%. The number of detected SLN was in the range of 1 to 6, with an average of 2 for each patient. The number of positive SLN was in significant correlation with the number of tumor-affected non-SNL (p<0,001). Further analysis showed that for each increase in the number of positive SLN by 1, the risk of positive non-SLN increased 6-fold, OR=6,22 (p<0,001). Conclusion: Use of methylene blue dye as a sole mapping agent when performing SLNB in patients with IDC is a reliable and effective method that can be safely implemented in medical institutions that lack availability of nuclear medicine services or significant monetary funds.