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While the effects of axial compression on beams have long been known, the effect of tensile axial loads on one-sided transversely cracked beams is less known. The crack namely shifts the position of the resultant of the axial normal stresses deeper into the uncracked part of the cross-section, and the crack tends to open, causing a transverse displacement. Therefore, this paper focuses on empirical modeling of the considered phenomenon for slender prismatic beams in order to establish a suitable 1D computational model based on detailed 3D FE mesh results. This goal can be achieved through the already established simplified model, where the crack is represented by an internal hinge endowed with a rotational spring. Several analyses of various beams differing in geometry, crack locations, and boundary conditions were executed by implementing 3D FE meshes to establish the appropriate model’s bending governing differential equation. After that, the corresponding parameter definitions were calibrated from the database of 3D FE models. By redefining the model’s input parameters, a suitable solution is achieved, offering a good balance between the results’ accuracy and the required computational effort. The functionality of the newly obtained solutions was verified through some comparative case studies that supplement the derivations.

Kako oziroma na kaksen nacin se kaže odlicnost organizacij pri dodajanju vrednosti za odjemalce? Namen je preveriti rezultate pri posameznih podgradnikih izbranega gradnika Dodajanje vrednosti za odjemalce v dveh razlicnih obdobjih in jih primerjati, kot tudi analizirati strokovno literaturo Uporabljeni in primerjani so bili rezultati izbranih obdobij FOS metra poslovne odlicnosti, kot tudi izvedena analiza strokovne literature Rezultati kažejo nihanja v podanih ocenah gradnika v izbranem obdobju, kar je lahko posledica razlicnih dejavnikov, hkrati pa strokovna literature potrjuje nase raziskovalno vprasanje, da odlicne organizacije upostevajo vsa nacela gradnika Dodajanje vrednosti za odjemalce S podanimi predlogi vplivamo na izboljsanje odlicnosti organizacij Z implementacijo predlogov lahko se izboljsamo vrednost za odjemalce ter s tem uspesnost organizacije na globalnem trgu Na dodano vrednost za odjemalce vplivajo vsi deležniki tako v kot zunaj organizacije Zavedati se je potrebno, da le preplet vseh in zasledovanje vseh nacel gradnika omogoca odlicnost organizacije Ker so rezultati tudi iz leta 2020, pomeni, da so to zadnji rezultati podgradnikov, zato lahko opazimo vpliv glavnega dejavnika (Covid-19) na rezultate Za dosego reprezentativnih rezultatov bi bilo potrebno primerjati se rezultate iz prejsnjih let in analizirati napredek/nazadovanje pri posameznih podgradnikih Alternate abstract:How or in what way is the excellence of companies in adding value for customers manifested? The purpose is to check the results of individual sub-subsets of the selected widget called Adding Value for Clients in two different periods and to compare them The results of selected periods have been used and compared, and we analyse them and, based on the analysis, propose measures for improvements The results show fluctuations in the given building block estimates over the selected period, which may be due to various factors With the given suggestions, we influence the improvement of the company's excellence By implementing the proposals, we can further improve the value for customers Value added for customers is influenced by all stakeholders in the company - management and employees It is necessary to be aware that they can only be more successful together and with consistent implementation of measures Since the results are also from 2020, it means that these are the latest results of the sub-builders, so we can see the influence of the main factor (Covid 19) on the results In order to achieve representative results, it would be necessary to compare the results from previous years and analyse the progress / decline in individual subcontractors

Context Younger age at treatment onset with conventional therapy (phosphate salts and active vitamin D; Pi/D) is associated with improved growth and skeletal outcomes in children with X-linked hypophosphatemia (XLH). The effect of age on burosumab efficacy and safety in XLH is unknown. Objective This work aimed to explore the efficacy and safety of burosumab vs Pi/D in younger ( Methods This post hoc analysis of a 64-week, open-label, randomized controlled study took place at 16 academic centers. Sixty-one children aged 1 to 12 years with XLH (younger, n = 26; older, n = 35) participated. Children received burosumab starting at 0.8 mg/kg every 2 weeks (younger, n = 14; older, n = 15) or continued Pi/D individually titrated per recommended guidelines (younger, n = 12; older, n = 20). The main outcome measure included the least squares means difference (LSMD) in Radiographic Global Impression of Change (RGI-C) rickets total score from baseline to week 64. Results The LSMD in outcomes through 64 weeks on burosumab vs conventional therapy by age group were as follows: RGI-C rickets total score (younger, +0.90; older, +1.07), total Rickets Severity Score (younger, −0.86; older, −1.44), RGI-C lower limb deformity score (younger, +1.02; older, +0.91), recumbent length or standing height Z-score (younger, +0.20; older, +0.09), and serum alkaline phosphatase (ALP) (younger, −31.15% of upper normal limit [ULN]; older, −52.11% of ULN). On burosumab, dental abscesses were not reported in younger children but were in 53% of older children. Conclusion Burosumab appears to improve outcomes both in younger and older children with XLH, including rickets, lower limb deformities, growth, and ALP, compared with Pi/D.

Patients who are fully recovered from a concussion may still be more vulnerable in the face of subsequent concussions. This study examines symptoms associated with repeated concussions in young and otherwise healthy adults.Cross sectional.Institutional study at a university setting.University students with a history of concussion.Participants were grouped based on numbers of concussions.The impact of incremental concussion on symptom clusters in Sport Concussion Assessment Tools 5 and Spearman ranking correlation coefficients between symptom clusters.One hundred thirty-five participants reported having had 1 concussion, 63 reported 2 concussions, 50 reported 3 concussions, and 43 reported 4 to 6 concussions. Total severity scores over the range of concussion number (1, 2, 3, and greater than 3) did not show a clear incremental effect. However, average scores of cognitive symptoms rose with each subsequent concussion ( P ≤ 0.05). The largest incremental effect observed was that of second concussions on emotional symptom scores (t = 5.85, P0.01). Symptoms in the emotional and cognitive clusters were the most correlated regardless of the number of reported concussions; the correlations were lowest with symptoms associated with sensitivity to light or noise.The incremental rise of cognitive symptom scores with each concussion affirms the importance of cognitive impairment in concussion assessment and implies a cumulative brain vulnerability that persists even after symptom resolution. The cognitive-emotional symptom clusters may reflect underlying concussion-induced impairments in the corticostriatothalamocortical (CSTC) networks, although sensitivity symptoms are potentially attributable to different neural correlates.

This paper derives an original finite element for the static bending analysis of a transversely cracked uniform beam resting on a two-parametric elastic foundation. In the simplified computational model based on the Euler–Bernoulli theory of small displacements, the crack is represented by a linear rotational spring connecting two elastic members. The derivations of approximate transverse displacement functions, stiffness matrix coefficients, and the load vector for a linearly distributed load along the entire beam element are based on novel cubic polynomial interpolation functions, including the second soil parameter. Moreover, all derived expressions are obtained in closed forms, which allow easy implementation in existing finite element software. Two numerical examples are presented in order to substantiate the discussed approach. They cover both possible analytical solution forms that may occur (depending on the problem parameters) from the same governing differential equation of the considered problem. Therefore, several response parameters are studied for each example (with additional emphasis on their convergence) and compared with the corresponding analytical solution, thus proving the quality of the obtained finite element.

The burden of disease of X-linked hypophosphatemia (XLH) in East Asia is poorly understood. This was a cross-sectional study using an online questionnaire to evaluate health-related quality of life (HRQOL) and disease complications in Japanese and Korean patients with XLH. Adults with XLH and the caregivers of children

Context We characterized linear growth in infants and children with X-linked hypophosphatemia (XLH). Objective Provide linear growth curves for children with XLH from birth to early adolescence. Design Data from 4 prior studies of XLH were pooled to construct growth curves. UX023-CL002 was an observational, retrospective chart review. Pretreatment data were collected from 3 interventional trials: two phase 2 trials (UX023-CL201, UX023-CL205) and a phase 3 trial (UX023-CL301). Setting Medical centers with expertise in treating XLH. Patients Children with XLH, 1-14 years of age. Intervention None. Main Outcome Measure Height-for-age linear growth curves, including values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for children with XLH compared to population norms. Results A total of 228 patients (132 girls, 96 boys) with 2381 height measurements were included. Nearly all subjects (> 99%) reported prior management with supplementation therapy. Compared to the Center for Disease Control and Prevention growth curves, boys at age 3 months, 6 months, 9 months, 1 year, and 2 years had median height percentiles of 46%, 37%, 26%, 18%, and 5%, respectively; for girls the median height percentiles were 52%, 37%, 25%, 18%, and 7%, respectively. Annual growth in children with XLH fell below that of healthy children near 1 year of age and progressively declined during early childhood, with all median height percentiles < 8% between 2 and 12 years old. Conclusion Children with XLH show decreased height gain by 1 year of age and remain below population norms thereafter. These data will help evaluate therapeutic interventions on linear growth for pediatric XLH.

X-linked hypophosphataemia in children is characterised by elevated serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphataemia, rickets, lower extremity bowing, and growth impairment. We compared the efficacy and safety of continuing conventional therapy, consisting of oral phosphate and active vitamin D, versus switching to burosumab, a fully human monoclonal antibody against FGF23, in paediatric X-linked hypophosphataemia.In this randomised, active-controlled, open-label, phase 3 trial at 16 clinical sites, we enrolled children with X-linked hypophosphataemia aged 1-12 years. Key eligibility criteria were a total Thacher rickets severity score of at least 2·0, fasting serum phosphorus lower than 0·97 mmol/L (3·0 mg/dL), confirmed PHEX (phosphate-regulating endopeptidase homolog, X-linked) mutation or variant of unknown significance in the patient or a family member with appropriate X-linked dominant inheritance, and receipt of conventional therapy for at least 6 consecutive months for children younger than 3 years or at least 12 consecutive months for children older than 3 years. Eligible patients were randomly assigned (1:1) to receive either subcutaneous burosumab starting at 0·8 mg/kg every 2 weeks (burosumab group) or conventional therapy prescribed by investigators (conventional therapy group). Both interventions lasted 64 weeks. The primary endpoint was change in rickets severity at week 40, assessed by the Radiographic Global Impression of Change global score. All patients who received at least one dose of treatment were included in the primary and safety analyses. The trial is registered with ClinicalTrials.gov, number NCT02915705.Recruitment took place between Aug 3, 2016, and May 8, 2017. Of 122 patients assessed, 61 were enrolled. Of these, 32 (18 girls, 14 boys) were randomly assigned to continue receiving conventional therapy and 29 (16 girls, 13 boys) to receive burosumab. For the primary endpoint at week 40, patients in the burosumab group had significantly greater improvement in Radiographic Global Impression of Change global score than did patients in the conventional therapy group (least squares mean +1·9 [SE 0·1] with burosumab vs +0·8 [0·1] with conventional therapy; difference 1·1, 95% CI 0·8-1·5; p0·0001). Treatment-emergent adverse events considered possibly, probably, or definitely related to treatment by the investigator occurred more frequently with burosumab (17 [59%] of 29 patients in the burosumab group vs seven [22%] of 32 patients in the conventional therapy group). Three serious adverse events occurred in each group, all considered unrelated to treatment and resolved.Significantly greater clinical improvements were shown in rickets severity, growth, and biochemistries among children with X-linked hypophosphataemia treated with burosumab compared with those continuing conventional therapy.Ultragenyx Pharmaceutical and Kyowa Kirin International.

Context X-linked hypophosphatemia (XLH) is characterized by excess fibroblast growth factor 23 (FGF23), hypophosphatemia, skeletal abnormalities, and growth impairment. We aimed to understand the burden of disease of XLH across the lifespan. Methods Responses were collected from adults with XLH and parents/caregivers of a child with XLH in an online survey, including multiple-choice and open-ended questions on demographics, disease manifestations, treatment history, assistive device use, and age-specific patient-reported outcomes (PROs). Results Data were collected from 232 adults with XLH (mean age, 45.6 years; 76% female) and 90 parents/caregivers of a child with XLH (mean age, 9.1 years; 56% female). Mean age recalled for symptom onset was 3.2 years for adults and 1.3 years for children. When surveyed, nearly all children (99%) and 64% of adults were receiving oral phosphate, active vitamin D, or both. Prior participation in a trial investigating burosumab, a fully human monoclonal antibody against FGF23, was reported in 3% of children and 10% of adults; of these respondents, only one child reported current treatment with burosumab at the time of the survey. Both children and adults reported typical features of XLH, including abnormal gait (84% and 86%, respectively), bowing of the tibia/fibula (72% and 77%), and short stature (80% and 86%). Nearly all adults (97%) and children (80%) reported bone or joint pain/stiffness. Adults reported a history of fractures (n/N = 102/232; 44%), with a mean (SD) age at first fracture of 26 (16) years. Adults reported osteophytes (46%), enthesopathy (27%), and spinal stenosis (19%). Mean scores for PROs evaluating pain, stiffness, and physical function were worse than population norms. Analgesics were taken at least once a week by 67% of adults. Conclusions Despite the common use of oral phosphate and active vitamin D established in the 1980s, children with XLH demonstrate a substantial disease burden, including pain and impaired physical functioning that persists, as demonstrated by similar responses reported in adults with XLH.