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Sedimentary charcoal records are widely used to reconstruct regional changes in fire regimes through time in the geological past. Existing global compilations are not geographically comprehensive and do not provide consistent metadata for all sites. Furthermore, the age models provided for these records are not harmonised and many are based on older calibrations of the radiocarbon ages. These issues limit the use of existing compilations for research into past fire regimes. Here, we present an expanded database of charcoal records, accompanied by new age models based on recalibration of radiocarbon ages using IntCal20 and Bayesian age-modelling software. We document the structure and contents of the database, the construction of the age models, and the quality control measures applied. We also record the expansion of geographical coverage relative to previous charcoal compilations and the expansion of metadata that can be used to inform analyses. This first version of the Reading Palaeofire Database contains 1676 records (entities) from 1480 sites worldwide. The database (RPDv1b – Harrison et al., 2021) is available at https://doi.org/10.17864/1947.000345.

The cyber security education market has grownup exponentially, with a CAGR of 13.9 % as reported by Data Intelo. The report published by the World Economic Forum 2023 indicates a shortfall of 2.27 million cyber security experts in 2021 across different roles and hence manifest that Skill-based cyber security education is the need of the hour. Cybersecurity as a field has evolved as a multi-discipline, multi-stakeholder and multi-role discipline. Therefore, the need to address formal education with an outcome-based philosophy is imperative to address for a wider audience with varied past training in their formal education. With the Internet becoming an essential part of human life, providing security of data passed over the Internet is becoming increasingly crucial. Therefore, the role in the organization which is quite demanding is to have expertise in handling and configuring network security, a subdomain of cyber security as a priority area. The rapid increase in the network attack landscape is constantly demanding monitoring of network attacks as well as a need to promote collaborative R&D and education in the sphere of cyber security due to a shortage of skilled resources. Platform-based education is a potential direction to achieve the objective and address the skill gap required in cyber security. The present research proposes a comprehensive web-based platform that can be used to communicate, collaborate and practice various use cases in the domain of network intrusion detection tools using machine learning algorithms and to evaluate user experience. The proposed platform CySecLearn is a collection of various functionalities and features that ensure experiential learning, will help the learner to develop critical thinking and expertise in network security and promote digital literacy in the domain of cyber security.

Wildfire occurrence is influenced by climate, vegetation and human activities. A key challenge for understanding the risk of fires is quantifying the mediating effect of vegetation on fire regimes. Here, we explore the relative importance of Holocene land cover, land use, dominant functional forest type, and climate dynamics on biomass burning in temperate and boreo-nemoral regions of central and eastern Europe over the past 12 kyr. We used an extensive data set of Holocene pollen and sedimentary charcoal records, in combination with climate simulations and statistical modelling. Biomass burning was highest during the early Holocene and lowest during the mid-Holocene in all three ecoregions (Atlantic, continental and boreo-nemoral) but was more spatially variable over the past 3–4 kyr. Although climate explained a significant variance in biomass burning during the early Holocene, tree cover was consistently the highest predictor of past biomass burning over the past 8 kyr. In temperate forests, biomass burning was high at ∼45 % tree cover and decreased to a minimum at between 60 % and 70 % tree cover. In needleleaf-dominated forests, biomass burning was highest at ∼ 60 %–65 % tree cover and steeply declined at >65 % tree cover. Biomass burning also increased when arable lands and grasslands reached ∼ 15 %–20 %, although this relationship was variable depending on land use practice via ignition sources, fuel type and quantities. Higher tree cover reduced the amount of solar radiation reaching the forest floor and could provide moister, more wind-protected microclimates underneath canopies, thereby decreasing fuel flammability. Tree cover at which biomass burning increased appears to be driven by warmer and drier summer conditions during the early Holocene and by increasing human influence on land cover during the late Holocene. We suggest that long-term fire hazard may be effectively reduced through land cover management, given that land cover has controlled fire regimes under the dynamic climates of the Holocene.

As global business and education environments become increasingly cross-cultural, prolonged stress faced by individuals navigating unfamiliar territories can lead to symptoms of burnout. This study explores the relationship between expatriate stress and Cultural Intelligence, considering moderating factors such as age, motivation, length of experience, and age group.

Abstract Yield multi-location trials associated to geostatistical techniques with environmental covariables can provide a better understanding of G x E interactions and, consequently, adaptation limits of soybean cultivars. Thus, the main objective of this study is understanding the environmental covariables effects on soybean adaptation, as well as predicting the adaptation of soybean under environmental variations and then recommend each soybean cultivar to favorable environments aiming maximize the average yield. The trials were carried out in randomized block design (RBD) with three replicates over three years, in 28 locations. Thirty-two genotypes (commercial and pre-commercial) representing different maturity groups (7.5–8.5) were evaluated in each trial were covering the Edaphoclimatic Region (REC) 401, 402 and 403. The covariables adopted as environmental descriptors were accumulated rainfall, minimum temperature, mean temperature, maximum temperature, photoperiod, relative humidity, soil clay content, soil water avaibility and altitude. After fitting means through Mixed Linear Model, the Regression-Kriging procedure was applied to spacialize the grain yield using environmental covariables as predictors. The covariables explained 32.54% of the GxE interaction, being the soil water avaibility the most important to the adaptation of soybean cultivars, contributing with 7.80%. Yield maps of each cultivar were obtained and, hence, the yield maximization map based on cultivar recommendation was elaborated.

BackgroundInternalizing disorders (IDs), primarily depression and anxiety, are highly prevalent among adolescents receiving community-based treatment for substance use disorders (SUDs). For such clients, interventions that do not holistically address both SUDs and IDs are less effective. ObjectiveThis pilot treatment development study aims to develop and test a modular treatment protocol for addressing cooccurring IDs among adolescents (aged 13 to 18 years) enrolled in routine care for substance use problems: Family Support Protocol for Adolescent Internalizing Disorders (Fam-AID). As an adjunctive protocol, Fam-AID will not require clinicians to markedly alter existing base practices for SUD. It will be anchored by 3 evidence-based foundations for treating cooccurring adolescent IDs: family engagement techniques, transdiagnostic individual cognitive behavioral therapy techniques, and family psychoeducation and safety planning. MethodsThis quasi-experimental study will proceed in 2 stages. The pilot stage will use rapid-cycle prototyping methods in collaboration with end-user stakeholders to draft protocol delivery and fidelity guidelines adapted from existing resources, solicit provider and client input on protocol content and delivery via cognitive interviewing, and pilot prototype components on 4 to 6 cases. The second stage will be an interrupted time series study for 60 comorbid SUD+ID cases across 2 sites serving diverse adolescents: 30 will receive treatment as usual (TAU); following clinician training in the protocol, 30 new cases will receive TAU enhanced by Fam-AID. For aim 1, the focus is on evaluating the acceptability of the Fam-AID protocol through therapist and client interviews as well as assessing fidelity benchmarks using therapist- and observer-reported protocol fidelity data. For aim 2, the plan is to compare the effects of TAU only cases versus TAU+Fam-AID cases on family treatment attendance and on adolescent ID and substance use symptoms, with measurements taken at baseline and at 3-month and 6-month follow-ups. ResultsStudy recruitment will begin in April 2025. ConclusionsWe anticipate that Fam-AID will contain 5 treatment modules that can be delivered in any sequence to meet client needs: family engagement of primary supports in treatment planning and services; relational reframing of family constraints, resiliencies, and social capital connected to the adolescent’s ID symptoms; functional analysis of the adolescent’s ID symptoms and related behaviors; cognitive behavioral therapy to address the adolescent’s ID symptoms and functional needs, featuring 3 core techniques (emotion acceptance, emotional exposure, and behavioral activation) to address negative affect and emotional dysregulation; and family psychoeducation and safety planning focused on education about comorbid SUD+ID and prevention of adolescent self-harm. If the abovementioned modules are found to be feasible and effective, Fam-AID will offer a set of pragmatic interventions to SUD clinicians for treating cooccurring IDs in adolescent clients. Trial RegistrationClinicalTrials.gov NCT06413979; https://www.clinicaltrials.gov/study/NCT06413979 International Registered Report Identifier (IRRID)PRR1-10.2196/64332

IntroductionRecent findings demonstrate that high density lipoprotein (HDL) function rather than HDL-cholesterol levels themselves may be a better indicator of cardiovascular disease risk. One mechanism by which HDL can become dysfunctional is through oxidative modification by reactive aldehydes. Previous studies from our group demonstrated that HDL modified by reactive aldehydes alters select cardioprotective functions of HDL in macrophages. To identify mechanisms by which dysfunctional HDL contributes to atherosclerosis progression, we designed experiments to test the hypothesis that HDL modified by reactive aldehydes triggers endoplasmic reticulum (ER) stress in primary murine macrophages.Methods and resultsPeritoneal macrophages were harvested from wild-type C57BL/6J mice and treated with thapsigargin, oxLDL, and/or HDL for up to 48 hours. Immunoblot analysis and semi-quantitative PCR were used to measure expression of BiP, p-eIF2α, ATF6, and XBP1 to assess activation of the unfolded protein response (UPR). Through an extensive set of comprehensive experiments, and contrary to some published studies, our findings led us to three novel discoveries in primary murine macrophages: (i) oxLDL alone was unable to induce ER stress; (ii) co-incubation with oxLDL or HDL in the presence of thapsigargin had an additive effect in which expression of ER stress markers were significantly increased and prolonged as compared to cells treated with thapsigargin alone; and (iii) HDL, in the presence or absence of reactive aldehydes, was unable blunt the ER stress induced by thapsigargin in the presence or absence of oxLDL.ConclusionsOur systematic approach to assess the role of native and modified HDL in mediating primary macrophage ER stress led to the discovery that lipoproteins on their own require the presence of thapsigargin to synergistically increase expression of ER stress markers. We further demonstrated that HDL, in the presence or absence of reactive aldehydes, was unable to blunt the ER stress induced by thapsigargin in the presence or absence of oxLDL. Together, our findings suggest the need for more detailed investigations to better understand the role of native and modified lipoproteins in mediating ER stress pathways.

The accurate diagnosis of brain tumour is very important in modern neuro-oncology medicine. Magnetic resonance spectroscopy (MRS) is supposed to be a promising tool for detecting cancerous lesions. However, the interpretation of MRS data is complicated by the fact that not all cancerous lesions exhibit elevated choline (Cho) levels. The main goal of our study was to investigate the lack of Cho lesion /Cho ref elevation in the population of grade II-III gliomas. 89 cases of gliomas grade II and III were used for the retrospective analysis – glioma (astrocytoma or oligodendroglioma) grade II (74 out of 89 cases [83%]) and III (15 out of 89 cases [17%]) underwent conventional MRI extended by MRS before treatment. Histopathological diagnosis was obtained either by biopsy or surgical resection. Gliomas were classified to the group of no-choline elevation when the ratio of choline measured within the tumour (Cho lesion ) to choline from NABT (Cho ref ) were equal to or lower than 1. Significant differences were observed between ratios of Cho lesion /Cr lesion calculated for no-choline elevation and glial tumour groups as well as in the NAA lesion /Cr lesion ratio between the no-choline elevation group and glial tumour group. With consistent data concerning choline level elevation and slightly lower NAA value, the Cho lesion /NAA lesion ratio is significantly higher in the WHO II glial tumour group compared to the no-choline elevation cases ( p < 0.000). In the current study the results demonstrated possibility of lack of choline elevation in patients with grade II-III gliomas, so it is important to remember that the lack of elevated choline levels does not exclude neoplastic lesion.

BackgroundCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression.MethodsWe retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone.ResultsFive hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1–76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6–26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3–94.8%] compared to 21.1% [95% CI 12.2–31.7%] for patients with non-tailored treatment.ConclusionsTailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.

Objectives: Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug. Methods: We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients’ characteristics, rituximab levels and anti-rituximab antibodies. Results: The analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria. Conclusion: In order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.

Abstract Circulating tumor HPV DNA (ctHPV16) assessed in liquid biopsy may be used as a marker of cancer in patients with HPV-associated oropharyngeal cancer (HPV + OPC). Factors influencing the initial ctHPV16 quantity are not well recognized. In this study we aimed to establish what factors are related to the level of ctHPV16 at the time of diagnosis. 51 patients (37 men and 14 women, median age of 57 years old) with HPV + OPC prior to definitive treatment were included. ctHPV16 was measured by qPCR. Tumor and nodal staging were assessed according to AJCC8. Blood derived factors included squamous cell carcinoma antigen (SCC-Ag), serum soluble fragment of cytokeratin 19 (CYFRA 21-1), C-reactive protein (CRP), albumin level (Alb), neutrophils (Neut), thrombocytes (Plt) and lymphocyte (Lym) count, Neut/Lym ratio were assessed. The volumes of the primary tumor (TV) and involved lymph nodes (NV) were calculated using MRI, CT or PET-CT scans. Data were analysed using parametric and nonparametric methods. Variables for multivariable linear regression analysis were chosen based on the results from univariable analysis (correlation, univariable regression and difference). There were 9 (18%), 10 (19%) and 32 (63%) patients who had TV and NV assessed in MRI, CT or PET respectively. Primary tumor neither as T-stage nor TV was related to ctHPV16 level. Significant differences in the ctHPV16 between patients with high vs low pain (P = 0.038), NV (P = 0.023), TV + NV (P = 0.018), CYFRA 21-1 (P = 0.002), CRP (P = 0.019), and N1 vs N3 (P = 0.044) were observed. ctHPV16 was significantly associated with CYFRA 21-1 (P = 0.017), N stage (P = 0.005), NV (P = 0.009), TV + NV (P = 0.002), CRP (P = 0.019), and pain (P = 0.038). In univariable linear regression analysis the same variables predicted ctHPV16 level. In multivariable analyses, CYFRA 21-1 and CRP (both as categorical variables) were predictors of ctHPV16 level even above NV. ctHPV16 at presentation is driven by tumor volume measured mostly by N. CYFRA 21-1 and CRP are additional factors related to ctHPV16 prior to the treatment.

Thromboinflammation/immunothrombosis plays a role in several diseases including thrombotic thrombocytopenic purpura (TTP) and COVID-19. Unlike the extensive research that has been conducted on COVID-19 cytokine storms, the baseline and acute phase cytokine profiles of TTP are poorly characterized. Moreover, we compared the cytokine profiles of TTP and COVID-19 to identify the disease-specific/general characteristics of thromboinflammation/immunothrombosis. Plasma concentrations of 33 soluble mediators (SMs: cytokines, chemokines, soluble receptors, and growth factors) were measured by multiplex bead-based LEGENDplex™ immunoassay from 32 COVID-19 patients (32 non-vaccinated patients in three severity groups), 32 TTP patients (remission/acute phase pairs of 16 patients), and 15 control samples. Mainly, the levels of innate immunity-related SMs changed in both diseases. In TTP, ten SMs decreased in both remission and acute phases compared to the control, one decreased, and two increased only in the acute phase compared to remission, indicating mostly anti-inflammatory changes. In COVID-19, ten pro-inflammatory SMs increased, whereas one decreased with increasing severity compared to the control. In severe COVID-19, sixteen SMs exceeded acute TTP levels, with only one higher in TTP. PCA identified CXCL10, IL-1RA, and VEGF as the main discriminators among their cytokine profiles. The innate immune response is altered in both diseases. The cytokine profile of TTP suggests a distinct pathomechanism from COVID-19 and supports referring to TTP as thromboinflammatory rather than immunothrombotic, emphasizing thrombosis over inflammation as the driving force of the acute phase.

BackgroundScreening, brief intervention, and referral to treatment for adolescents (SBIRT-A) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care. Existing SBIRT-A procedures rely almost exclusively on adolescents alone, despite the recognition of caregivers as critical protective factors in adolescent development and AOD use. Moreover, controlled SBIRT-A studies conducted in primary care have yielded inconsistent findings about implementation feasibility and effects on AOD outcomes and overall developmental functioning. There is urgent need to investigate the value of systematically incorporating caregivers in SBIRT-A procedures. ObjectiveThis randomized effectiveness trial will advance research and scope on SBIRT-A in primary care by conducting a head-to-head test of 2 conceptually grounded, evidence-informed approaches: a standard adolescent-only approach (SBIRT-A-Standard) versus a more expansive family-based approach (SBIRT-A-Family). The SBIRT-A-Family approach enhances the procedures of the SBIRT-A-Standard approach by screening for AOD risk with both adolescents and caregivers; leveraging multidomain, multireporter AOD risk and protection data to inform case identification and risk categorization; and directly involving caregivers in brief intervention and referral to treatment activities. MethodsThe study will include 2300 adolescents (aged 12-17 y) and their caregivers attending 1 of 3 hospital-affiliated pediatric settings serving diverse patient populations in major urban areas. Study recruitment, screening, randomization, and all SBIRT-A activities will occur during a single pediatric visit. SBIRT-A procedures will be delivered digitally on handheld tablets using patient-facing and provider-facing programming. Primary outcomes (AOD use, co-occurring behavior problems, and parent-adolescent communication about AOD use) and secondary outcomes (adolescent quality of life, adolescent risk factors, and therapy attendance) will be assessed at screening and initial assessment and 3-, 6-, 9-, and 12-month follow-ups. The study is well powered to conduct all planned main and moderator (age, sex, race, ethnicity, and youth AOD risk status) analyses. ResultsThis study will be conducted over a 5-year period. Provider training was initiated in year 1 (December 2023). Participant recruitment and follow-up data collection began in year 2 (March 2024). We expect the results from this study to be published in early 2027. ConclusionsSBIRT-A is widely endorsed but currently underused in pediatric primary care settings, and questions remain about optimal approaches and overall effectiveness. In particular, referral to treatment procedures in primary care remains virtually untested among youth. In addition, whereas research strongly supports involving families in interventions for adolescent AOD, SBIRT-A effectiveness trial testing approaches that actively engage family members in primary care are absent. This trial is designed to help fill these research gaps to inform the critical health decision of whether and how to include caregivers in SBIRT-A activities conducted in pediatric primary care. Trial RegistrationClinicalTrials.gov NCT05964010; https://www.clinicaltrials.gov/study/NCT05964010 International Registered Report Identifier (IRRID)PRR1-10.2196/54486

Under the era of circular economy, the deposit-refund system (DRS) for e.g. polyethylene terephthalate (PET) is thought to be a good choice to achieve a more structured plastic recycling. The present research has the aim to make a comprehensive description and a practical guideline in order to evaluate how collection and separation system influence the quality and efficiency of mechanical recycling of PET. The DRS has been symbolized by manually collected bottles with (BCL) and without (B) caps and labels. Samples have been given from the selective income (SI) and the sorting residue (SR) of a manual selective waste sorting plant and PET fraction of refuse derived fuel (RDF). Based on preliminary qualification results such as melt flow indices (MFI), PET bottles are worth selecting into the main colours like water clear, blue, and all the others together, referred to as PET-A, PET-B, and PET-D fractions of the sorting plant. The SR seemed to be a beneficial raw material for PET recycling as both mechanical and rheological properties were proper enough. PET separated from the Mechanical Biological Treatment (MBT) plant as RDF showed the worst processing and mechanical properties, but both can be improved with deeper precleaning. X-ray tomography (CT) scans have shown a correlation between the source of waste and the gas void structure which influence the macroscopic mechanical properties.

Artykuł obejmuje teoretyczne i empiryczne opracowanie problematyki przestępcy gospodarczego. Na początku artykuł zawiera teoretyczne omówienie najważniejszych kwestii dotyczących przestępczości gospodarczej, a kolejno zagadnienia związane z działaniami resocjalizacyjnymi ukierunkowanymi na usprawnienie decyzji prospołecznych. Artykuł prezentuje również wyniki jakościowej analizy decydenta – przestępcy gospodarczego, który w wywiadzie pogłębionym prezentuje narracyjną perspektywę dotyczącą motywów działania, emocji, oceny własnej osoby, a także planów na swoją przyszłość. Zakończenie to wnioski z badań i wskazówki dla praktyki ujęte w kontekście edukacji ustawicznej.

The purpose of this paper is to explore how the travel habits of Ukrainian tourists changed after the beginning of the 2022 war in Ukraine in comparison to the year 2021. The theoretical part of the paper discusses the impacts of war on tourism; in the empirical part, the secondary and the primary research on the Ukrainians’ travel habits before and during the war is performed. The research gives an insight into the frequency of travelling, planned spending on travel, ethnic dilemmas on travelling, and travel destinations. The research is essential in the context of war and post-war periods for understanding the psychological and behavioral effects, assessing economic consequences, addressing destination marketing and recovery efforts, and facilitating reconciliation and social integration. Research limitations include the scope and generalizability of the findings, self-reporting biases, causality and temporal issues, and limited timeframe and context.

Background and Objectives: Rheumatoid arthritis (RA) patients experience sarcopenia and decreased muscle mass and handgrip strength, leading to decreased quality of life and disability. The prevalence of RA varies across regions. This study aimed to evaluate the factors associated with RA in Croatian regional centres and explore correlations between clinical parameters and muscle strength. Materials and Methods: Included in this study were 267 stable RA patients from four Croatian clinical centres. The patients’ mean age was 60.4 ± 12.0 years, with 12.7% of them being male. For each study participant, information was gathered on their anthropometric characteristics, clinical and laboratory indicators, quality of life, disease activity, and sociodemographics. Results: The main results showed that in the female RA participants, the significant positive predictors are weight, height, exercise, VAS, and haemoglobin level. The negative predictors are the use of conventional synthetic disease-modifying anti-rheumatic drugs, the use of biological disease-modifying anti-rheumatic drugs, the number of tender joints, the number of swollen joints, the estimated sedimentation rate, the C-reactive protein, the disease activity score, the parameters of the EQ5D, and being prescribed with three or more medications. In the male RA participants, significant predictors of muscle strength are only weight, height, and anxiety/depression difficulties, according to the EQ5D. Conclusions: This study showed correlations between muscle strength and the parameters of disease activity, inflammation parameters, health-related quality of life, therapy, and exercise in the female RA participants in Croatia.

Background. The use of locoregional radiotherapy (RT) in patients with advanced ER-positive, HER2-negative breast cancer remains a topic of ongoing debate. In this study, we aimed to evaluate the efficacy of locoregional RT in advanced breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in a first-line setting. Methods. We conducted a retrospective analysis of patients diagnosed with advanced breast cancer between 2018 and 2023 who received treatment with CDK4/6i and underwent locoregional radiotherapy. Results. Among the 371 patients treated with CDK4/6i as part of their first-line therapy, 23 received locoregional RT either concurrently or sequentially with CDK4/6 inhibitors. Disease progression within the breast occurred in 19 patients (5.1%). Among these cases, five patients had previously undergone breast RT (5/23, 21.7%), while 14 did not (14/348, 4.0%, p = 0.004). All cases of local progression after RT followed palliative doses and were accompanied by early systemic progression. The 2-year PFS in the entire cohort of patients treated with locoregional RT was 65.7% (95% CI: 40.5–82.3%). Notably, patients who received higher RT doses had longer 2-year PFS (83.3%, 95% CI: 27.3–97.5%) than those with palliative RT doses (59.3%, 95% CI: 30.7–79.3%); however, the results were not statistically significant (p = 0.58). Furthermore, the 2-year local control in the entire cohort with locoregional RT was 73.0% (95% CI: 46.5–87.9%). Importantly, no local progression was observed after RT when using high doses. Conclusions. The addition of locoregional radiotherapy to first-line CDK4/6 inhibitors warrants further investigation across various clinical scenarios in advanced breast cancer. Palliative radiation regimens delivered early in breast oligoprogression may not always suffice, emphasizing the need for comprehensive studies in this context.

Many governments worldwide are increasingly using developments in information and communication technologies (ICT) to provide online services to their citizens. This process is commonly referred to as e-government. South Africa is one of the leading nations in technology and overall development in the Sub-Saharan-African region. Nevertheless, South Africa has failed to successfully implement a wide range of e-Government services for its population over the past years. This paper focuses on analyzing the success factors for a seamless implementation of eGovernment systems and how countries such as Kenya, which are not a developed as South Africa, were able to adapt and successfully implement functioning systems for their citizens. The theoretical research results have indicated what the main success factors are in e-government implementation. Further analysis has been conducted to find out what the reasons are that South Africa has a non-functioning e-government system. An embedded case study approach has been selected to focus on selected aspects of the case study. The paper provides a comprehensive overview of the current state of e-government services in South Africa and compares it with other Sub-Saharan countries with similar economic conditions. This comparison allows for a better understanding of the challenges and opportunities faced by South Africa in improving its e-government services.

Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration.Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport.Results: Mean ± SD ivacaftor oral bioavailability was 18.4 ± 3.2% and 16.2 ± 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 ± 1.61% and 4.35 ± 1.84%, respectively.Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.

The Nurse Professional Development Model (NPD) has been utilized to improve quality of care for several conditions. Patients with Parkinson’s Disease (PD) are susceptible to higher risks while in the hospital. Educational efforts for this patient population are challenged by the small, disbursed number of patients as well as increased turn-over and reliance on temporary nursing staff. To properly care for this patient group, any education has to be hospital wide and ongoing for maintenance of competency. We have used the NPD Model to initiate education for new incoming nurses as well as for continued education for a program that requires hospital-wide reach. Our utilization of the NPD Model for this high risk, low volume patient population has helped us improve the safety of this patient population in the hospital. With this manuscript we detail the need and the educational platform with the hope of it serving as a reference for other institutions facing similar challenges.

BackgroundPatients with Parkinson’s disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using “custom” ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital.Material and methodsWe reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed.Results14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group (p

Therapist-report measures of evidence-based interventions have enormous potential utility as quality indicators in routine care; yet, few such tools have shown strong psychometric properties. This study describes reliability and validity characteristics of a therapist-report measure of family therapy techniques for treating adolescent conduct and substance use problems: Inventory of Therapy Techniques for Core Elements of Family Therapy (ITT-CEFT). Study participants included 31 staff therapists treating 68 adolescent clients in eight community-based mental health and substance use clinics. Therapists submitted ITT-CEFT checklists and companion audio recordings for 189 sessions. The ITT-CEFT contains 13 techniques identified as core elements of three manualized family therapy models that are empirically supported for the target group. Therapists also reported on their use of three motivational interventions, and independent observers coded the submitted recordings. ITT-CEFT factor validity was shown via confirmatory factor analyses of the tool's theoretical structure. Derived modules were: Family Engagement (four items; Cronbach's [alpha] = 0.72); Relational Orientation (five items; [alpha] = 0.74); and Interactional Change (four items; [alpha] = 0.66). Concurrent validity analyses showed fair-to-excellent therapist reliability compared to observer ratings (ICCs range 0.64--0.75); they showed moderate therapist accuracy compared to observer mean scores, reflecting a tendency to overestimate delivery of the techniques. Discriminant validity analyses showed tool differentiation from motivational interventions. Results offer provisional evidence for the feasibility of using the therapist-report ITT-CEFT to anchor quality procedures for family therapy interventions in real-world settings.