As different scientific disciplines begin to converge on machine learning for causal inference, we demonstrate the application of machine learning algorithms in the context of longitudinal causal estimation using electronic health records. Our aim is to formulate a marginal structural model for estimating diabetes care provisions in which we envisioned hypothetical (i.e. counterfactual) dynamic treatment regimes using a combination of drug therapies to manage diabetes: metformin, sulfonylurea and SGLT-2i. The binary outcome of diabetes care provisions was defined using a composite measure of chronic disease prevention and screening elements [27] including (i) primary care visit, (ii) blood pressure, (iii) weight, (iv) hemoglobin A1c, (v) lipid, (vi) ACR, (vii) eGFR and (viii) statin medication. We used several statistical learning algorithms to describe causal relationships between the prescription of three common classes of diabetes medications and quality of diabetes care using the electronic health records contained in National Diabetes Repository. In particular, we generated an ensemble of statistical learning algorithms using the SuperLearner framework based on the following base learners: (i) least absolute shrinkage and selection operator, (ii) ridge regression, (iii) elastic net, (iv) random forest, (v) gradient boosting machines, and (vi) neural network. Each statistical learning algorithm was fitted using the pseudo-population generated from the marginalization of the time-dependent confounding process. Covariate balance was assessed using the longitudinal (i.e. cumulative-time product) stabilized weights with calibrated restrictions. Our results indicated that the treatment drop-in cohorts (with respect to metformin, sulfonylurea and SGLT-2i) may have improved diabetes care provisions in relation to treatment naïve (i.e. no treatment) cohort. As a clinical utility, we hope that this article will facilitate discussions around the prevention of adverse chronic outcomes associated with type II diabetes through the improvement of diabetes care provisions in primary care.

The aim of this research was to determine the influence of the SiO2/Al2O3 molar ratio on the specific commercial properties of NaA zeolite subtypes as final market products (4A,4A-AG and 4A-MS) under the real production and process conditions. The value of the SiO2/Al2O3 molar ratio, so-called silicate module, was set as independently variable and the effect on the physical and chemical properties of each of the subtypes of NaA zeolites was examined. The paper investigates how the SiO2/Al2O3 molar ratio affects specific properties of NaA powders, namely the ion exchange capacity, oil adsorption capacity and water adsorption capacity. Some previous theoretical and experimental studies have shown that the molar ratio plays a crucial role in the formation of these very similar but for final application different subtypes of NaA zeolite. The experimental part of this work was performed and tested in real production conditions, which can be considered as an advantage in relevance to the obtained results. Various analytical and instrumental testing methods were used for the analysis of the obtained powders, including SEM, XRD and PSD analyses.

This study analyzes how service-learning contributes to the level of commitment to environmental sustainability in higher education institutions (HEIs), as perceived by their students. The empirical analysis has been conducted by using the PLS-SEM modelling, on a sample of 366 undergraduate students of business from Croatia and Bosnia & Herzegovina. The obtained results support the hypothesized influence of the service-learning development level on the sustainability commitment in higher education. We also consider the indirect effects within the model. They show that service-learning mediates the relationships between students’ idealism and sustainability commitment, as well as between students’ social trust and sustainability commitment. Implications of obtained empirical results for theory and higher education practice are discussed. The potential for generalizing results for other sustainability interventions is assessed.

Abstract Background CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. Aim The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. Subjects and methods Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. Results In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. Conclusion In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.

A range of the distinctive physical properties, comprising high surface-to-volume ratio, possibility to achieve mechanical and chemical stability after a tailored treatment, controlled quantum confinement and the room-temperature photoluminescence, combined with mass production capabilities offer porous silicon unmatched capabilities required for the development of electro-optical devices. Yet, the mechanism of the charge carrier dynamics remains poorly controlled and understood. In particular, non-radiative recombination, often the main process of the excited carrier's decay, has not been adequately comprehended to this day. Here we show, that the recombination mechanism critically depends on the composition of surface passivation. That is, hydrogen passivated material exhibits Shockley-Read-Hall type of decay, while for oxidised surfaces, it proceeds by two orders of magnitude faster and exclusively through the Auger process. Moreover, it is possible to control the source of recombination in the same sample by applying a cyclic sequence of hydrogenation-oxidation-hydrogenation processes, and, consequently switching on-demand between Shockley-Read-Hall and Auger recombinations. Remarkably, irregardless of the recombination mechanism, the rate constant scales inversely with the average volume of individual silicon nanocrystals contained in the material. Thus, the type of the non-radiative recombination is established by the composition of the passivation, while its rate depends on the degree of the charge carriers' quantum confinement.

The purpose of this study was to assess the antioxidant activity of the fresh extracts of Croatian and Greek watermelon seeds. Samples were prepared using two extraction methods: Soxhlet and maceration. Ethanol was used as a solvent in the Soxhlet, and methanol in the maceration method. The mass fractions of the extracts obtained by maceration were lower compared to those obtained by the Soxhlet method. The antioxidant capacity of fresh watermelon-seed extracts was determined by DPPH (2,2-diphenyl-1-picrylhydrazyl radical) method. The antioxidant capacity of the extracts was also expressed via IC 50 (half maximal inhibitory concentration). Based on the obtained IC 50 values (1.41 to 2.60 mg ml −1 ), all tested extracts showed antiradical activity but antioxidant capacity was better in extracts obtained by the maceration method. The reason for this may be the use of methanol as a solvent, which was to be expected, since methanol is a more polar solvent than ethanol. The neutralisation capacity of DPPH radicals of analysed extracts was compared to the neutralisation capacity of ascorbic acid as standard. The concentrations of tested extracts required to neutralize 50 % of DPPH radicals were significantly higher than the required concentration of ascorbic acid (0.25 mg ml −1 ).

Feminist care ethics has become a prominent ethical theory that influenced theoretical and practical discussions in a variety of disciplines and institutions on a global scale. However, it has been criticized by transnational feminist scholars for operating with Western-centric assumptions and registers, especially by universalizing care as it is practiced in the Global North. It has also been criticized for prioritizing gender over other categories of intersectionality and hence for not being truly intersectional. Given the imperialist and colonial legacies embedded into the unequal distribution of care work across the globe, a Western-centric approach may also carry the danger of paternalism. Hence, a critical approach to care ethics would require reckoning with these challenges. The aim of this article is first to unfold these discussions and the responses to them from care ethics scholars and then to present resources in Beauvoir’s existentialist ethics, specifically the tenet of treating the other as freedom, as productive tools for countering the Western-centric and paternalistic aspects of care practices.

In modern systems that rely on the use of battery management systems (BMS), longevity and the re-use of battery packs have always been important topics of discussion. These battery packs would require warehouse storage together with adequate monitoring and configuration prior to their reintegration into new systems. Traditional use of wired connections can be very cumbersome, and sometimes even impossible, due to the outer layers and packaging. To circumvent these issues, we propose an extension to the conventional BMS design that incorporates the use of near field communication (NFC) for the purpose of wireless battery pack status readout. Additionally, to ensure that these packs are only managed by authenticated devices and that the data communicated with is protected against outside eavesdropping and tampering, we present a solution in the form of a lightweight security layer on top of the NFC protocol. To show the feasibility of our design, an accompanying prototype has been implemented and evaluated.

The paper deals with the mathematical modeling and control of an unmanned aerial vehicle (UAV), called octocopter, based on a linear quadratic regulator (LQR). The complex multivariable and nonlinear UAV model is linearized and represented in the state space form. Optimal LQR control system, which is composed of combination the altitude (UAV height - ${z}$ position) and attitude (orientation) controllers, was first designed. Then, this system is extended to provide an additional control of the translation movement in ${x}$ and ${y}$ directions. The proposed LQR control structure is capable of controlling the UAV for all position and orientation coordinates while tracking desired 3D trajectory. Simulation studies are performed on the UAV model where the designed LQR controller has been compared with previously developed PD controller.

The paper addresses the problem of detecting pedestrians using three dimensional data acquired by an autonomous mobile robot equipped with an on-board 3D laser scanner. Previous works in this field have dealt with various approaches for combining 2D and 3D range data features for the use in pedestrian classification. In this paper we propose an image processing pipeline for generating a depth image from point clouds data and then localizing object candidates from the depth image. It involves the image segmentation, feature extraction and human classification processes within unstructured dynamic environments. Three different approaches for the detection of pedestrians, vehicles and cyclists using only 3D range data were employed as a part of this system. We train and test the classifiers in an open environment, with presence of multiple pedestrians, cyclists and vehicles, using only point cloud data. The effectiveness and robustness of the proposed system are verified through experiments with real data. This system is also capable to deal with a real-time framerate (10Hz) with high accuracy.

BACKGROUND The exposed pulp has been the topic of numerous studies, but well-designed and well-executed comparative trials on the outcome and treatment of these teeth have been limited. OBJECTIVES This study was conducted to answer the following questions: in patients with non-traumatic pulpitis associated with no or non-spontaneous pain in permanent teeth, (i) is direct pulp capping or pulpotomy (partial/full) as effective as selective or stepwise caries removal [Population/participants, Intervention(s), Comparator(s)/control, Outcome(s) (PICO) 1], (ii) is pulpotomy (partial/full) as effective as direct pulp capping (PICO 2), and (iii) is pulpotomy (partial/full) as effective as a pulpectomy (PICO 3), in terms of a combination of patient and clinical reported outcomes, with "tooth survival" as the most critical outcome? METHODS A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception to November 3rd 2021. Grey literature and contents of the major subject journals were examined. Eligibility criteria followed the PICO questions. Two independent reviewers performed study selection, data extraction, and appraisal; disagreements were resolved by a third reviewer. The risk of bias was assessed by the revised Cochrane risk-of-bias tool for randomized trials. RESULTS Three randomized clinical trials (RCTs) were included in the review. No study fulfilled the criteria to answer PICO 1. There were no significant differences in the reported outcomes between investigated treatments in all included RCTs. None of the included studies reported the most critical outcome "tooth survival". A high loss of patients during the follow-up period was observed. DISCUSSION Although a few studies fulfilled strict eligible criteria, the results of this systematic review clearly highlight a paucity of available evidence. At the present time, clinical decisions cannot be substantiated by direct comparative trials. CONCLUSIONS Based on limited evidence, this systematic review discovered no significant differences in effectiveness between compared vital pulp treatments in managing non-traumatic pulpitis associated with no or nonspontaneous pain. Further high-quality RCTs are necessary to investigate the effectiveness of direct pulp capping or pulpotomy (partial/full) compared to selective or stepwise caries removal.

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.

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).

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.

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.