Analysis of mechanical properties of external unilateral fixation device „ Ultra X “, in the case of torque load, is presented in this paper. Fixation device is applied on lower leg in the case of unstable fracture. Computer aided design (CAD) model and finite element model (FEM) are developed according to the dimensions and material properties of real fixation device. In the next step principal stress and deformation analysis is performed in CATIA V5 software. During numerical analysis values of stresses at critical places are monitored and analyzed. In addi - tion, values of displacements are measured on important places on fixation device and bone fracture. Using values of displacements at the place of bone fracture, stiffness of the fracture is calculated. The same methodology is used to calculate stiffness of the fixation device. Using obtained results, several conclusions about the mechanical properties of the fixation device “Ultra X” are formulated at the end of the paper.

Introduction: Heart failure (HF) still remains as one of the most common causes of hospital admission with a high mortality rate. Aim: To investigate the possible prognostic role of brain natriuretic peptide (BNP), high-sensitivity (hs) cardiac troponin (cTn) I, cystatin C, and cancer antigen 125 (CA125) in the prediction of decompensation after an index hospitalization and to investigate their possible additive prognostic value. Patients and Methods: Two hundred twenty-two patients hospitalized with acute HF were monitored and followed for 18 months. Results: BNP at discharge has the highest sensitivity and specificity in the prediction of decompensation. For a cutoff value of 423.3 pg/ml, sensitivity was 64.3% and specificity was 64.5%, with a positive predictive value of 71.6% and an area under the curve (AUC) of 0.69 (P < 0.001). The hazard risk (HR) for decompensation when the discharge BNP was above the cutoff value was 2.18. Cystatin C, at a cutoff value of 1.46 mg/L, had a sensitivity of 57% and specificity of 57.8%, with a positive predictive value of 65.8% and an AUC of 0.59 (P = 0.028). CA125, in the prediction of decompensation in patients with acute heart failure (AHF) and at a cutoff value of 80.5 IU/L, had a sensitivity of 60.5% and specificity of 53.3%, with a positive predictive value of 64.5% and an AUC of 0.59 (P = 0.022). The time till onset of decompensation was significantly shorter in patients with four versus three elevated biomarkers (P = 0.047), with five versus three elevated biomarkers (P = 0.026), and in patients with four versus two elevated biomarkers (P = 0.026). The HR for decompensation in patients with five positive biomarkers was 3.7 (P = 0.001) and in patients with four positive biomarkers was 2.5 (P = 0.014), compared to patients who had fewer positive biomarkers. Conclusion: BNP, cystatin C, and CA125 are predictors of decompensation, and their combined usage leads to better prediction of new decompensation.

3115 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with BRCA1/2 mut treated with Tala are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 1 mg of Tala orally daily until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test (alpha 0.10; 82% power). Secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR) and SD, and safety. DOR is defined as time from pt’s first documented objective response (OR) to progressive disease (PD). Duration of SD is defined as time from tx start to PD. Results: 28 pts with 16 solid tumors (6/28 pts had lung cancer) with BRCA1 (n=9) , BRCA2 (n=16) , or BRCA1/2 (n=3) mut were enrolled from Dec 2019 to Sept 2021. All pts were included in efficacy analyses. Demographics and outcomes are shown. 1 CR, 9 PR and 6 SD16+ were observed for a DC rate of 57% (1-sided 90% CI: 43% to 100%) and an OR rate of 36% (95% CI: 19% to 56%); the null hypothesis of a 15% DC rate was rejected (p<0.001). 11/16 pts with OR or SD16+ had a BRCA2 mut, 4 had BRCA1 mut, and 1 had both. The pt with a CR (duration of 93 wks) had non-melanoma skin cancer, with BRCA2 and ATM muts, and was microsatellite instability high with 41 muts per megabase. Pts with PR had various solid tumors; 6/9 pts had BRCA2 mut, 2 had BRCA1 mut , 1 had both. Of pts with DC, 11 had tumor types for which PARP inhibitors are not yet FDA approved. Median duration of PR was 20 wks (range, 11-80). 10/16 pts with DC had a co-alteration in the 24 homologous recombination-related genes examined, mainly ATM (3) or ARID1A (2). 13 pts had ≥1 grade 3 tx-related adverse or serious adverse events including: anemia, AST or bilirubin increase, hyponatremia, nausea, vomiting, neutrophil, platelet, or white blood cell decrease. Conclusions: Tala demonstrated antitumor activity in heavily pretreated pts with advanced solid tumors with BRCA1/2 mut. Additional study is warranted to confirm the efficacy of Tala in non-breast, non-ovarian cancer pts with BRCA1/2 mut. Clinical trial information: NCT02693535 . [Table: see text]

3117 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in cohorts of pts with breast cancer (BC) and other solid tumors with PIK3CA mut treated with T are reported. Methods: Eligible pts had BC or other solid tumors, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. After antihistamine pre-tx, 25 mg of T was infused over 30-60 minutes once weekly until disease progression. Primary endpoint was disease control (DC), defined as complete or partial (PR) response, or stable disease of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. For the BC cohort, Simon’s optimal 2-stage design with null DC rate of 15% vs. 35% (power=0.85, α=0.10) was used with stage 1 (n=10) stopping for futility if < 2/10 pts had DC. Low accruing histology-specific cohorts with PIK3CA and T tx were collapsed into 1 histology-pooled (HP) cohort. For the HP cohort, the hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test with α=0.10. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: 12 pts with PIK3CA mut with BC and 29 pts with PIK3CA mut in other solid tumors (across 9 tumor types) were enrolled. 2 pts (1 in each cohort) were found to be ineligible after enrolling and were not included in efficacy analyses. Demographics and outcomes for each cohort are shown. At the end of stage 1 in the BC cohort, 1 PR was observed for DC and OR rates of 9%; the cohort was closed for futility (p=0.83). For the HP cohort, 3 PR and 5 SD16+ were observed for DC rate of 29% (p=0.049) and OR rate of 11%; the null hypothesis was rejected. Cancer types in pts with OR or SD16+ included cervical, ovarian and head/neck; most common muts were H1047R/L (3), E545K (2) and E542K (2). 1 pt with ovarian and H1047R has ongoing PR at 86 wks. 11/41 pts had ≥1 tx-related grade 3-4 adverse or serious adverse event, including anemia, headache, hyperglycemia, hypertension, hypertriglyceridemia, mucositis oral, lymphocyte, neutrophil or platelet count decrease, pneumonitis, and sepsis. Conclusions: Although T does not appear to have antitumor activity in pts with BC with PIK3CA mut, it does show antitumor activity in pts with other solid tumors with PIK3CA mut and warrants further study. Clinical trial information: NCT02693535 . [Table: see text]

Alcohol drinking is an important health-related problem and one of the major risk factors for a wide array of non-communicable diseases, while there is a lack of studies investigating environment-specific associations between sports participation and alcohol drinking in adolescence. This study prospectively investigated the relationship between sports factors (i.e., participation in sports and competitive achievement), with the prevalence of harmful alcohol drinking (HD), and HD initiation in 14-to-16 years old adolescents from Bosnia and Herzegovina (n = 641, 337 females, 43% living in rural community). Participants were tested over 4-time points divided by approximately 6 months, from the beginning of high school to the end of the second grade. Variables included gender, factors related to sport participation, a community of residence (urban or rural), and outcome: alcohol consumption was assessed by the AUDIT questionnaire. Results evidenced that the prevalence of HD increased over the study period from 6 to 19%, with no significant differences between urban and rural youth. Logistic regression for HD as criterion evidenced adolescents who participated in sports and then quit as being at particular risk for drinking alcohol at the study baseline. Sports factors were not correlated with HD initiation in the period between 14 and 16 years of age. It seems that the problem of alcohol drinking should be preventively targeted in all youth, irrespective of living environment. Although sports participation was not evidenced as being a factor of influence on HD initiation, results highlight the necessity of developing targeted preventive campaigns against alcohol drinking for adolescents who quit sports.

Objective: To investigate the arterial stiffness and risk factors in adolescence. Arterial stiffness often (AS) results from the degenerative process of the media layer of elastic arteries causing rigidity of the arteries. Arterial stiffness increases with age and it is associated with several risk factors as a disease predictor. But, arterial stiffness can be also increased in a healthy arteries as well. The increased sympathetic activity promotes vasoconstriction of resistant blood vessels i.e. arteries and arterioles that result in peripheral vasoconstriction. Adolescence age is the most important period of life for promoting future health. The certain dynamic risk factors in adolescence like, emotional dysregulation, psychological family stress, education pressure, lack of sleep, gambling, substance abuse, smartphone overuse and obesity can cause arterial stiffness. Design and method: The prospective open randomized study was designed. Adolescence age between 10 and 19 years have been investigated for increased arterial stiffness and risk factors. The inclusion criteria was healthy adolescence, while exclusion criteria was any disorder present. Arterial stiffness, non-invasive blood pressure and pulse wave datas have been measured using Agedio device. The risk factors were evaluated in every subject. The vascular age have been outlined as the final measure. Results: The preliminary results indicate the increase of Augmentation Index and Coefficient of Reflection. The average percentage of Augmentation Index was 40% and Coefficient of Reflection 65% (normal value 28% and 60% respectively). The main risk factors were educational pressure, lack of sleep and smartphone influence. The vascular age was on average, 3 years higher than biological age. Conclusions: Arterial stiffness in adolescence is increased mainly by peripheral vasoconstriction, manifested with Augmentation index and Coefficient of wave Reflection.

For any three circles in the plane where each circle is tangent to the other two, the Descartes’ theorem yields the existence of a fourth circle tangent to the starting three. Continuing this process by adding a new circle between any three tangent circles leads to Apollonian packings. The fractal structures resulting from infinite continuation of such processes are known as Apollonian gaskets. Close-packed dimer configurations on such structures are well modeled by perfect matchings in the corresponding graphs. We consider Apollonian gaskets for several types of initial configurations and present explicit expressions for the number of perfect matchings in such graphs

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Introduction Medical adhesives are adhesives used in medical devices to establish and maintain contact with the body over a period of time (usually by application to the skin) and are widely used in most care settings. Application of medical adhesives to the skin can lead to skin stripping, mild or severe allergic reactions and skin irritation that may manifest as redness, itching or rash. Adhesive-related skin injury can lead to infection, delayed wound healing and an increased risk of scarring. These injuries can cause severe discomfort and pain, and can affect the patient’s quality of life. A systematic review summarising patient’s experiences on this topic will contribute to informing adhesive producers and policy makers, and guiding further development and improvement of available technologies. Methods and analysis This systematic review protocol is based on the principles of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline. A systematic search will be conducted in CINAHL, EMBASE, MEDLINE and PsycINFO. In addition, manual searches will be performed, reviewing the reference lists of relevant reviews and articles included for quality assessment. Qualitative studies using various methods will be considered for inclusion. Screening of title, abstract and full text will be done by two reviewers. The methodological quality of studies under consideration will be critically assessed by two reviewers using the Joanna Briggs Institute Critical Appraisal Tool for Qualitative Research. Data extraction will be performed independently by two reviewers using a predefined data extraction form. Meta-aggregation will be used to summarise the evidence. Ethics and dissemination No ethical approval or consent is required because no participants will be recruited. This systematic review protocol is published in an open access journal to increase transparency of the research methods used. Results will be disseminated at national and international conferences.

Abstract In today’s increasingly connected and digitized business environment, brands face numerous challenges that can significantly affect their reputation and value, and one of the key challenges that many organizations across the world face is brand risk. Due to its role in many aspects of business, the main purpose of this paper is to revitalize this phenomenon by exploring it through bibliometric indicators, publishing trends and analyzing it through the current literature. In this sense, the paper adresses two research questions, both related to revealing the scope and nature of brand risk as the construct of a great relevance in many scientific fields, whereas a special attention has been given to the analysis of the most cited papers on this matter. The findings show that the construct although presented two decades ago is still in infancy phase, and quite neglected in the current body of knowledge.

Sleep is extremely important for physical and mental health. Although polysomnography is an established approach in sleep analysis, it is quite intrusive and expensive. Consequently, developing a non-invasive and non-intrusive home sleep monitoring system with minimal influence on patients, that can reliably and accurately measure cardiorespiratory parameters, is of great interest. The aim of this study is to validate a non-invasive and unobtrusive cardiorespiratory parameter monitoring system based on an accelerometer sensor. This system includes a special holder to install the system under the bed mattress. The additional aim is to determine the optimum relative system position (in relation to the subject) at which the most accurate and precise values of measured parameters could be achieved. The data were collected from 23 subjects (13 males and 10 females). The obtained ballistocardiogram signal was sequentially processed using a sixth-order Butterworth bandpass filter and a moving average filter. As a result, an average error (compared to reference values) of 2.24 beats per minute for heart rate and 1.52 breaths per minute for respiratory rate was achieved, regardless of the subject’s sleep position. For males and females, the errors were 2.28 bpm and 2.19 bpm for heart rate and 1.41 rpm and 1.30 rpm for respiratory rate. We determined that placing the sensor and system at chest level is the preferred configuration for cardiorespiratory measurement. Further studies of the system’s performance in larger groups of subjects are required, despite the promising results of the current tests in healthy subjects.

Blue Biotechnology is developing rapidly worldwide. However, the Nagoya Protocol (NP), Responsible Research and Innovation (RRI) and other regulatory requirements in this field are falling behind. This article identifies the main RRI, NP, and regulatory gaps and provides key recommendations to mitigate these challenges.

Takotsubo syndrome (TTS) is an acute heart failure syndrome characterised by catecholamine-induced oxidative tissue damage. Punica granatum, a fruit-bearing tree, is known to have high polyphenolic content and has been proven to be a potent antioxidant. This study aimed to investigate the effects of pomegranate peel extract (PoPEx) pre-treatment on isoprenaline-induced takotsubo-like myocardial injury in rats. Male Wistar rats were randomised into four groups. Animals in the PoPEx(P) and PoPEx + isoprenaline group (P + I) were pre-treated for 7 days with 100 mg/kg/day of PoPEx. On the sixth and the seventh day, TTS-like syndrome was induced in rats from the isoprenaline(I) and P + I groups by administering 85 mg/kg/day of isoprenaline. PoPEx pre-treatment led to the elevation of superoxide dismutase and catalase (p < 0.05), reduced glutathione (p < 0.001) levels, decreased the thiobarbituric acid reactive substances (p < 0.001), H2O2, O2− (p < 0.05), and NO2− (p < 0.001), in the P + I group, when compared to the I group. In addition, a significant reduction in the levels of cardiac damage markers, as well as a reduction in the extent of cardiac damage, was found. In conclusion, PoPEx pre-treatment significantly attenuated the isoprenaline-induced myocardial damage, primarily via the preservation of endogenous antioxidant capacity in the rat model of takotsubo-like cardiomyopathy.