Importance The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood. Objective To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss. Design, Setting, and Participants In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021. Exposures According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only, (3) mixed activity, or (4) clinical stability. Main Outcomes and Measures Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models. Results Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-3.0]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, -0.36; 95% CI, -0.60 to -0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, -0.18; 95% CI, -0.34 to -0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity. Conclusions and Relevance Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.

Attention Deficit Hyperactivity Disorder (ADHD) is a frequent neurodevelopmental disorder characterized by hyperactivity, inattention, and impul- sivity. The issue of whether ADHD is a socially constructed disorder has received much attention. The goal of the present study was to examine the clinical prevalence of ADHD in Bosnia and Herzegovina (BIH). An additional goal was to investigate the prevalence of school-aged children who fulfill the criteria for the condition but do not have a clinical diagnosis. For the first research goal, the sample consisted of five University Clinical Centers in BIH that provided data on the prevalence. For the second goal, the sample consisted of 1935 parents of children aged 6 to 15 years. Parents of 1935 school-aged children from the Federation BIH completed the questionnaire regarding ADHD symptoms. Children ranged in age from 6 to 15 years. The mean age of children was 10.2 years (SD- 2.1 years). There were 1061 girls and 874 boys in the sample. Five hospitals in the Federation BIH (4 University Clinical Centers and 1 Cantonal Hos- pital) were sent a questionnaire to provide us with information on how many school-aged children were diagnosed with ADHD and their basic demographic data. In addition, the Clinical Centers were asked to provide information on what treatment they provide to children with ADHD. The results of this study indicated that clinical diagnosis of ADHD is infrequent. The number of clinically confirmed cases of ADHD in the Federation BIH was 138 or less than 0.001%. On the other hand, accord ing to survey data, there is a prevalence rate of ADHD indicated like that observed in western countries. According to the parents’ reports, there were 97 children or 5% who fulfilled the criteria for ADHD diagnosis. In relation to gender distribution of ADHD, there were more boys (88 boys) than girls (50 girls) with a clinically confirmed diagnosis of ADHD and boys were 1.76 times more likely to have a ADHD diagnosis than were girls. On the other hand there were more girls than boys who had ADHD according to parents’ reports, but this difference, according to the Chi square test, was not statistically significant (ꭓ 2 = 0.14; p = ,70). The results of this study have clearly shown that ADHD is underdiag- nozed in Bosnia and Herzegovina. There is a huge discrepancy between the clinically diagnosed children and the parent-reported symptoms of ADHD. Given the burden that ADHD has on children and their families it should be of the utmost importance to provide timely diagnosis and proper treatment. One way to improve the current situation is through a better cooperation between school staff (psychologists, teachers), parents, and medical professionals.

Abstract The rise of cyber-attacks coming up with the increased use of mobile devices and web services has initiated the growth of interest to understand the impact of Perception of Security (PoS) on Quality of Experience (QoE) in mobile web context and which factors impact PoS. This paper aims to investigate the relations among QoE, PoS, and multiple influence factors in different mobile web contexts. The obtained results have shown that PoS differently impacts QoE in considered mobile web contexts (banking, commerce, browsing, mail, and health). Also, the analyzed factors (risk, reliability and availability, 3rd party seals, privacy, security, grammar quality, aesthetics, reputation, brand name, and usability) have been assigned different weights of influence in terms of PoS in mobile web contexts. These findings open a wide range of potential research that could lead to the increase and improvement of users’ Quality of Life (QoL).

This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR002) of the Conference Proceedings. Citation Format: Alexander Coulton, Irene Lobon, Lavinia Spain, Andrew Rowan, Desiree Shnidrig, Scott Shepherd, Ben Shum, Fiona Byrne, Lewis Au, Kim Edmonds, Ellie Carlyle, Alexandra Renn, Christina Messiou, Charlotte Spencer, Andreas M. Schmidt, Zayd Tippu, Aljosja Rogiers, Max Emmerich, Camille Gerard, Husayn Pallikonda, Cristina Naceur-Lombardelli, Floris Foijer, Hilda van den Bos, René Wardenaar, Diana Spierings, Kate Young, Lisa Pickering, Andrew Furness, Elaine Borg, Miriam Mitchison, David Moore, Mary Falzon, Ian Proctor, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Charles Swanton, Mariam Jamal-Hanjani, Kevin Litchfield, Samra Turajlic. Advanced melanoma exhibits a diversity of evolutionary routes to lethality [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A012.

Despite recent advances in the treatment of advanced melanoma using immune checkpoint inhibitors (ICI), 5-year overall survival remains suboptimal. A clear understanding of the potential evolutionary trajectories of melanoma is needed in order to advance treatment and prognostic options. Here we present the Posthumous Evaluation of Advanced Cancer Environment (PEACE) study of advanced melanoma, revealing a diversity of evolutionary pathways to lethality. This interim analysis of our 50-patient cohort comprises 14 ICI-treated patients with a mixture of phenotypic subtypes, including cutaneous, acral, mucosal and melanoma of unknown primary. The sampling regime encompasses a broad range of visceral metastases from various organ sites, with a total of 573 tumor samples (an average of 40 samples per patient). Our data span a variety of modalities, including exomic, transcriptomic, panel sequencing, single cell sequencing, FISH, and radiological data. Clonal phylogenies of patients were diverse in structure: some followed a linear evolutionary trajectory with little to no branching, whereas others followed a branched evolutionary pattern. We also observed various patterns of metastatic seeding, with both monoclonal and polyclonal cases of seeding. In addition, patients treated with chemotherapy showed higher subclonal mutational burden than those without. As with previous literature, we found extensive copy number alterations in these advanced melanomas. In contrast, however, our data also reveal patients with no incidence of WGD, with previous work finding this to be a ubiquitous feature of advanced melanoma. In cases of WGD, the majority of copy number alterations were losses rather than gains. In terms of treatment resistance, we observed loss of heterozygosity in key genes of the antigen presentation pathway (most notably B2M), and little signal of neoantigen loss via immunoediting, indicating that these tumors develop resistance to ICI regardless of neoantigen burden. A further question of interest was the determination of lesion-level factors influencing response to ICI treatment using radiological data. MYC amplification was significantly associated with non-responding lesions, whilst PBX1, a promoter of natural killer cells, was shown to be significantly amplified in responding lesions. Our single-cell data reveal a case of polyclonal seeding at the level of whole-genome doubling. This has implications for sample-level phylogenies that are inferred from copy-number status, indicating that intra-tumor heterogeneity at the level of copy number could confound these trees. We also find a potentially novel driver of melanoma, PHF3. This gene has previously been associated with UV DNA-damage response, however here it was found in a non-sun damaged melanoma to have a clonal, focal 7n copy number gain in an otherwise diploid cancer, with corresponding upregulation of expression. In summary, our study comprises an extensive intra-patient, multi-lesion analysis of advanced melanoma, with important implications in both technical and clinical settings. Citation Format: Alexander Coulton, Irene Lobon, Lavinia Spain, Andrew Rowan, Desiree Shnidrig, Scott Shepherd, Ben Shum, Fiona Byrne, Lewis Au, Kim Edmonds, Ellie Carlyle, Alexandra Renn, Christina Messiou, Charlotte Spencer, Andreas M. Schmidt, Zayd Tippu, Aljosja Rogiers, Max Emmerich, Camille Gerard, Husayn Pallikonda, Cristina Naceur-Lombardelli, Floris Foijer, Hilda van den Bos, René Wardenaar, Diana Spierings, Kate Young, Lisa Pickering, Andrew Furness, Elaine Borg, Miriam Mitchison, David Moore, Mary Falzon, Ian Proctor, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Charles Swanton, Mariam Jamal-Hanjani, Kevin Litchfield, Samra Turajlic. Advanced melanoma exhibits a diversity of evolutionary routes to lethality [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr PR002.

In the paper, the possibility of combining deep neural network (DNN) model compression methods to achieve better compression results was considered. To compare the advantages and disadvantages of each method, all methods were applied to the ResNet18 model for pretraining to the NCT-CRC-HE-100K dataset while using CRC-VAL-HE-7K as the validation dataset. In the proposed method, quantization, pruning, weight clustering, QAT (quantization-aware training), preserve cluster QAT (hereinafter PCQAT), and distillation were performed for the compression of ResNet18. The final evaluation of the obtained models was carried out on a Raspberry Pi 4 device using the validation dataset. The greatest model compression result on the disk was achieved by applying the PCQAT method, whose application led to a reduction in size of the initial model by as much as 45 times, whereas the greatest model acceleration result was achieved via distillation on the MobileNetV2 model. All methods led to the compression of the initial size of the model, with a slight loss in the model accuracy or an increase in the model accuracy in the case of QAT and weight clustering. INT8 quantization and knowledge distillation also led to a significant decrease in the model execution time.

Mucosa-associated invariant T (MAIT) cells are unconventional T cells with innate-like capacity to rapidly respond to microbial infection via MR1-restricted antigen recognition. Emerging evidence indicate that they can also act as rapid sensors of viral infection via innate cytokine activation. However, their possible role in the immune response to mRNA vaccination is unknown. Here, we evaluated the involvement of MAIT cells in individuals vaccinated with the BNT162b2 mRNA SARS-CoV-2 vaccine. MAIT cell levels, phenotype and function in circulation were preserved and unperturbed through day 35 post-vaccination in healthy donor (HD) vaccinees, as well as people living with HIV (PLWH) or with primary immunodeficiency (PID). Unexpectedly, pre-vaccination and post-vaccination levels of MAIT cells correlated positively with the magnitude of the SARS-CoV-2 spike protein-specific CD4 T cell and antibody responses in the HD vaccinees. This pattern was largely preserved in the PID group, but less so in the PLWH group. Furthermore, in the HD vaccinees levels of MAIT cell activation and cytolytic potential correlated negatively to the adaptive antigen-specific immune responses. These findings indicate an unexpected association between MAIT cell compartment characteristics and the immune response magnitude to the BNT162b2 mRNA vaccine.

Mucosa-associated invariant T (MAIT) cells are unconventional T cells with innate-like capacity to rapidly respond to microbial infection via MR1-restricted antigen recognition. Emerging evidence indicate that they can also act as rapid sensors of viral infection via innate cytokine activation. However, their possible role in the immune response to mRNA vaccination is unknown. Here, we evaluated the involvement of MAIT cells in individuals vaccinated with the BNT162b2 mRNA SARS-CoV-2 vaccine. MAIT cell levels, phenotype and function in circulation were preserved and unperturbed through day 35 post-vaccination in healthy donor (HD) vaccinees, as well as people living with HIV (PLWH) or with primary immunodeficiency (PID). Unexpectedly, pre-vaccination and post-vaccination levels of MAIT cells correlated positively with the magnitude of the SARS-CoV-2 spike protein-specific CD4 T cell and antibody responses in the HD vaccinees. This pattern was largely preserved in the PID group, but less so in the PLWH group. Furthermore, in the HD vaccinees levels of MAIT cell activation and cytolytic potential correlated negatively to the adaptive antigen-specific immune responses. These findings indicate an unexpected association between MAIT cell compartment characteristics and the immune response magnitude to the BNT162b2 mRNA vaccine.

PurposeThis study investigates the relationships between the four dimensions of organizational justice (OJ) (distributive, procedural, interpersonal, and informational) and employees' intention to stay (ITS) in organizations in Bosnia and Herzegovina while considering the mediating role of job satisfaction (JS).Design/methodology/approachThrough a cross-sectional questionnaire-based survey, 336 responses were collected from employees in private companies and non-governmental organizations. Structural equation modeling was performed to test the hypotheses.FindingsResults indicate support for the relationships between dimensions of OJ and ITS, except in the case of procedural justice (PJ). Similarly, JS is a full mediator in all relationships, except for PJ.Originality/valueThe study extends the literature by incorporating all four dimensions of OJ and testing them individually in relation to the ITS. Furthermore, the study deviates from a traditional approach of simple relationships by introducing the mediating role of JS. Finally, it contributes to the scarce literature in developing countries.

Abstract Background Parental education is one of the best predictors of child school achievement. Higher parental education is not only associated with higher child intelligence, but children from highly educated parents also perform better in school due to other family related factors. This study evaluates the relation between parental education, child non-verbal intelligence and parenting practices with child school achievement. Methods Longitudinal data from a large population-based, multi-ethnic cohort of children in the Netherlands (63% Dutch origin) followed from birth to age 13 years (3547 children; 52.3% girls) were analyzed. School achievement was measured at the end of primary school (12 years of age) with a national Dutch academic test score. Parental education was assessed at age 3 years. The non-verbal intelligence of the child was measured at age 6 years and a full intelligence was measured at age 13 years. Maternal and paternal family routines, harsh parenting and corporal punishment were assessed in early and mid-childhood. Mediation analysis was performed with the G-formula and Structural Equation Models. Results Child intelligence partially mediated [B indirect effect =0.54 95% CI (0.46, 0.62) P < 0.001] the association between parental education and child school achievement. Independent of intelligence, family routines [B indirect effect =0.04 95% CI (0.01, 0.07) P < 0.01], but not harsh parenting mediated this association. Conclusions Higher parental education was associated with better school achievement through two independent mechanisms, through higher intelligence of the child and parenting practices.

increasingly common occurrence of rain with a significant amount of precipitation in one hour, which causes floods. Floods cause great material and intangible damage per population and often endanger human lives. The road network in such situations has crucial importance to take urgent intervention measures and rescue people, animals and material goods. This paper is focused on the natural flood disaster and its influence on road infrastructure and presents the risk assessment methodology and determines critical road sections of main roads in the Federation of Bosnia and Herzegovina, analyzing data on 100-year floods.

Flooding is a significant threat to human-life, ecosystems, cultural heritage and society in general. A risk-based safety approach is necessary to support decision making and prioritize intervention measures, either during the response or during the prevention stage. As a consequence of flooding, transport infrastructure and flood protection system can be significantly damaged and cause cascading effects on other infrastructure. In this paper a risk assessment model will be presented for determining the direct and indirect impacts of flooding hazards in the case study area of city of Karlovac. The model is using the novel vulnerability assessment methods for embankments and bridges exposed to different flood hazard scenarios. The consequence analysis is using an improved quantification model for direct and indirect impacts of different flood hazard scenarios. These scenarios are then used for flood risk mapping, applied on the case study area.