External Control Research Articles

Phase 2 study of bizaxofusp, an IL-4R targeted toxin payload, in nonresectable recurrent GBM: Comparison of overall survival with contemporaneous eligibility-matched and propensity score balanced external control arm.

2079 Background: Bizaxofusp (MDNA55) is designed to selectively deliver a potent toxin payload to tumor cells by targeting the IL-4 receptor (IL-4R) overexpressed by GBM, but not normal brain. Localized delivery of bizaxofusp minimizes risk of off-target toxicities and systemic exposure while eliciting effective tumor cell killing. Bizaxofusp was evaluated using convection-enhanced delivery in MDNA55-05 (NCT02858895), a single-arm, open-label, multi-center Ph2 study in nonresectable recurrent GBM (rGBM). Methods: The study population comprised of de novo IDH wild-type GBM patients with 1st or 2nd relapse that were non-resectable. Forty-four patients were administered a single treatment of bizaxofusp (range: 18-240 μg). The primary endpoint was OS; secondary endpoints were safety and tumor response. IL-4R expression in tumor biopsies was determined using a validated assay. OS was compared to an eligibility matched external control arm (emECA) of 81 contemporaneous rGBM subjects receiving standard of care. The emECA was further refined by propensity-score balancing (pbECA) to the bizaxofusp arm based on known prognostic factors, resulting in a weighted sample size of 40.8. OS was defined as time from relapse (to unify index date in both arms) or treatment start (for analysis of tumor response) to death/censor. Tumor response was assessed following RANO and mRANO criteria. Results: Bizaxofusp showed an acceptable safety profile at doses up to 240 μg. TRAEs were primarily neurological or aggravation of pre-existing neurological deficits associated with GBM and were manageable with standard measures. Results showed that IL-4R expression did not impact mOS except in patients receiving low doses of bizaxofusp. The bizaxofusp arm had significantly longer median OS (mOS) than contemporaneous emECA (12.4 vs 7.7 months; HR: 0.64, 95% CI 0.46-0.93; p = 0.02). Survival benefit was also evident when compared to the pbECA: (12.4 vs 7.2 months; HR: 0.72, 95% CI 0.46-1.1; p = 0.27). Patients with tumor control (SD or PR/CR, n=21) had significantly longer mOS than patients with tumor progression (n=23) (16.7 vs 8.5 months; HR = 0.5, 95% CI 0.27-0.9; p = 0.01). Among patients with tumor control who had pseudoprogression (PsP) per mRANO, mOS (22.8 months) was significantly longer than patients with tumor progression (HR: 0.49, 95% CI 0.25-0.98; p = 0.049). Conclusions: Bizaxofusp achieved significant OS benefit in patients with nonresectable rGBM compared to contemporaneous emECA. Patients who experienced tumor control, including those with PsP, showed significantly longer survival than patients with tumor progression. Phase 3 ready registrational trial will comprise a high dose bizaxofusp arm and a hybrid control arm with 1/3 randomized subjects and 2/3 pmECA. Clinical trial information: NCT02858895 .

Historical change in trajectories of loneliness in old age: Older adults today are less lonely, but do not differ in their age trajectories.

To check claims of a "loneliness epidemic," we examined whether current cohorts of older adults report higher levels and/or steeper age-related increases in loneliness than earlier-born peers. Specifically, we used 1,068 age-matched longitudinal reports (Mage observations = 79 years, 49% women) of loneliness provided by independent samples recruited in the German city of Berlin in 1990 and 2010, n = 257 participants in the Berlin Aging Study (BASE) and n = 383 participants in Berlin Aging Study II (BASE-II). Using multilevel models that orthogonalize between-person and within-person age effects, we examined how responses to items from the UCLA Loneliness Scale provided by observation-matched cohorts differed with age and across cohorts, and if those differences might be explained by a variety of individual factors. Results revealed that at age 79, the later-born BASE-II cohort reported substantially lower levels of loneliness than the earlier-born BASE cohort (d = -0.84), with cohort differences accounting for more than 14% of the variance in loneliness. Age trajectories, however, were parallel without evidence of cohort differences in rates of within-person age-related changes in loneliness. Differences in gender, education, cognitive functioning, and external control beliefs accounted for the lion's share of cohort-related differences in levels of loneliness. Results show that loneliness among older adults has shifted to markedly lower levels today, but the rate at which loneliness increases with age proceeds similarly as 2 decades ago. Future studies should investigate how psychosocial functioning across the life course is progressing in different sociohistorical contexts and in other age groups, such as younger and middle-aged adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Bodily Autonomy and Trauma: Understanding the Nature of the Association Between Sexual Trauma, an External Locus of Control, and Depressive Symptoms.

There is growing evidence suggesting an increased perception of control is associated with reduced psychological distress among survivors of sexual trauma. The current study advances the extant literature by investigating the association between depressive symptoms, sexual trauma, and an external locus of control or the perception life events are outside one's own control. To do so, we analyze data from the New Family Structures Study, a nationally representative survey of U.S. adults ages 18-39. Results from ordinary least square regression analyses suggest sexual trauma and an external locus of control are associated with significantly greater depressive symptoms and that external control exacerbates the association between sexual trauma and depression. Such findings suggest future research should investigate environmental control for sexual trauma survivors in areas such as prenatal care and the justice system.

Evaluation of Automated Disk Diffusion Antimicrobial Susceptibility Testing Using Radian® In-Line Carousel

Antimicrobial susceptibility testing (AST) by disk diffusion provides an accurate image of bacterial growth, enabling the detection of culture purity, heterogeneous growth, and antibiotic interactions. However, this manual method is time-consuming and visual interpretation is prone to errors. To overcome these disadvantages, the Radian® In-Line Carousel (Copan, Brescia, Italy) was launched, which is a WASPLab® module dedicated to full automation of (pre)-analytical steps as well as interpretation of disk diffusion AST. However, until now, no evaluation of Radian® against manual disk diffusion has been performed. We assessed the categorical agreement (CA) between standardized disk diffusion (reference method) and Radian® using EUCAST 2021 breakpoints. We tested 135 non-duplicate strains, selected from the National EUCAST challenge panel, clinical strains, and external quality controls. The strains included Enterobacterales (n = 63), Enterococcus faecalis (n = 3), Enterococcus faecium (n = 10), Pseudomonas aeruginosa (n = 16), Staphylococcus aureus (n = 19), coagulase-negative staphylococci (n = 4), and Streptococcus spp. (n = 20). Furthermore, we explored antibiotic disk thermolability in the WASP Radian® carousel by testing 10 ATCC® strains up to 7 days. The observed CA was 95.3%, 96.3%, 93.8%, 97.3% and 98.0% for Enterobacterales, Enterococcus spp., P. aeruginosa, Staphylococcus spp. and Streptococcus spp., respectively, resulting in an acceptable overall CA for all groups. (Very) major error rates were ≤ 5% for all antibiotics. Antibiotic disk thermostability was confirmed up to 4 days in the WASP Radian® In-Line Carousel. The Radian® In-Line Carousel provides a fully automated solution for accurate disk diffusion AST, reducing workload and improving standardization and traceability. In addition, our study demonstrated the thermostability of antibiotic disks up to 4 days in the WASP Radian® In-Line Carousel.

Beyond the Classical Type I Error: Bayesian Metrics for Bayesian Designs Using Informative Priors

There is growing interest in Bayesian clinical trial designs with informative prior distributions, for example for extrapolation of adult data to pediatrics, or use of external controls. While the classical Type I error is commonly used to evaluate such designs, it cannot be strictly controlled and it is acknowledged that other metrics may be more appropriate. We focus on two common situations—borrowing control data or information on the treatment contrast—and discuss several fully probabilistic metrics to evaluate the risk of false positive conclusions. Each metric requires specification of a design prior, which can differ from the analysis prior and permits understanding of the behavior of a Bayesian design under scenarios where the analysis prior differs from the true data generation process. The metrics include the average Type I error and the pre-posterior probability of a false positive result. When borrowing control data, our empirical cases demonstrate that the average Type I error is asymptotically controlled (in certain cases strictly) when the analysis and design prior coincide. We illustrate use of these Bayesian metrics with real applications, and discuss how they could facilitate discussions between sponsors, regulators and other stakeholders about the appropriateness of Bayesian borrowing designs for pivotal studies.

Analytical performance evaluation of the Mindray enzymatic assay for hemoglobin A1c measurement

Hemoglobin A1c (HbA1c) plays a crucial role in diabetes management. We aimed to evaluate the analytical performance of a new enzymatic method kit for HbA1c measurement. The performance of the enzymatic method, including precision, accuracy, and linearity, was evaluated. Moreover, the interference effect from conventional interferents, Hb derivatives, Hb variants, and common drugs were assessed. In addition, the agreement of HbA1c results was compared between enzymatic methods, cation-exchange high-performance liquid chromatography (HPLC), and immunoassays. The intra-assay, between-assay, and total precision of HbA1c were all lower than 2%. HbA1c showed good linearity within the range of 3.96–20.23%. The enzymatic assay yielded results consistent with the external quality control samples, with a bias of less than ± 6% from the target values. The enzymatic method showed no interference from bilirubin, intralipid, vitamin C, Hb derivatives, common Hb variants, as well as antipyretic analgesics and hypoglycemic drugs. The HbA1c results of the enzymatic assay showed good agreement and accuracy compared to those obtained from the HPLC method and the immunoassay. The enzymatic method kit performed on the BS-600M chemistry analyzer is a reliable and robust method for measuring HbA1c. It is suitable for routine practice in clinical chemistry laboratories.

The ethical student scale: development of a new measure

Purpose The purpose of this study is to develop the “ethical student scale” to understand the underlying factors that lead to the decisions of cheating and plagiarism and where business students are developmentally from a moral perspective and to help academic institutions assess how best to develop ethical education throughout the curriculum. This three-dimensional nine-item scale based on Kohlberg’s moral development model is proposed to serve as a valuable tool for educators who are struggling with identifying the best approach to help their students make ethical choices both within and outside of the walls of their educational institutions and once they join the workforce. Design/methodology/approach Four survey design studies were conducted to determine what factors had previously been identified to both negatively and positively impact the propensity of a university student to engage in cheating and/or plagiarizing (Study 1, N = 179), to preliminarily validate the three dimension nine item scale that emerged from Study 1 (Study 2, N = 87); to test the construct validity of the three-dimensional nine-item scale (Study 3, N = 235); and to test the nine-item scale for convergent, divergent and predictive validity (Study 4, N = 201). The four surveys were administered to undergraduate students at two universities in the Northeast in the USA. Findings To shed light on the underlying factors that lead to the decisions of cheating and plagiarism, the authors propose three factors that are engaged when students make these types of ethical decisions: rules and enforcement as an external control, personal morality as an internal control and social influences as a social control (Kohlberg, 1976). Through four studies, this paper presents a three-dimensional nine-item scale based on Kohlberg’s moral development model to determine the factors that influence the propensity of a university student to engage in cheating and/or plagiarizing. The proposed scale showed strong reliability across the three dimensions. Research limitations/implications The limitations of the scale are that this research was restricted to an academic setting. The relationship between the academic environment, the resulting behaviors of students and the subsequent behavior of these students as managers also needs investigation to determine if business ethics education does have an impact on increasing ethical decision-making. Practical implications The ethical student scale attempts to measure the development stage of students in a university setting and has the potential utility to help higher education institutions better understand the moral development of their students and what drives their decisions to engage in an ethical manner. Being a short yet reliable tool, ethical student scale may help business schools develop programs beyond a single business ethics course to instill ethical decision-making in students. Social implications One of the goals as business educators is to produce ethical managers. The ethical student scale can help us develop a more integrated approach to business ethics education. As the students become managers and leaders in organizations, the social implications for more ethical decision-makers and organizations are widespread and vital to the community and the economy. Originality/value Ethical student scale is an attempt to quantify what types of controls (external, social, or personal) help develop ethical students and ethical managers. Based on Kohlberg’s moral development model, this three-dimensional nine-item scale which shows strong reliability will serve as a valuable tool for educators who are struggling with identifying the best approach to the issue of unethical decisions and behaviors as they try to create strategies to help their students make ethical choices both within and outside of the walls of their educational institutions and once they join the workforce.

Interference of Particles with Fermionic Internal Degrees of Freedom.

The interference of fermionic particles, specifically molecules comprising a small number of fermions, in a Mach-Zehnder interferometer is being investigated under the influence of both classical and non-classical external controls. The aim is to identify control strategies that can elucidate the relationship between the interference pattern and the characteristics of internal fermion-fermion interactions.

Comparing prospectively assigned trial and real-world lung cancer patients.

Aim: To evaluate the comparability of a probable clinical trial (CT) cohort derived from electronic medical records (EMR) data with a real-world cohort treated with the same therapy and identified using the same inclusion and exclusion criteria to emulate an external control. Methods: We utilized de-identified patient-level structured data sourced from EMRs. We then compared patterns of overall survival (OS) between probable CT patients with those drawn from non-contemporaneous real-world data (RWD) using a two-sided log-rank test, hazard ratios (HRs) using a Cox proportional-hazards model and Kaplan-Meier (KM) survival curves. Each regression estimate was calculated with a corresponding 95% confidence interval. We additionally conducted multiple matching methods to assess their relative performance. Results: Median (standard deviation) OS was 10.2 (0.7) months for the RWD arm and 11.3 (1.3) for the probable CT arm with a Log rank p-value equal to 0.4771. OS in both cohorts is longer than the reported CT median OS of 9.2 (0.6). The HRs generated under all five assessed matching methods (including without adjustment) were not statistically significant at the 95% confidence level. Conclusion: Our results suggest, with caveats noted, that survival patterns between real-world and CT cohorts in this NSCLC setting are not statistically significantly different.

Evaluation of Algal Control Measures in Eutrophic Reservoirs Based on Aquatic Ecosystem Models

The frequency of freshwater cyanobacterial blooms is increasing globally due to climate change and eutrophication, particularly in reservoirs. Reservoir ecosystems exhibit unique characteristics, and there is a complex relationship between factors such as light, temperature, nutrient salts, hydrology, and algal growth. The impact of the other factors on algal growth varies significantly among different reservoirs. Thus, it is crucial to assess the effectiveness of various algal control measures implemented in different reservoirs. This study conducted a comprehensive assessment by establishing a eutrophication model for the Shanzi Reservoir in Fuzhou City. The model incorporated meteorology, hydrology, carbon dynamics, nutrient cycling, and biological communities. The effectiveness of diverse management measures was systematically evaluated. The findings demonstrate that increasing the water level, reducing nutrient salts in sediments, and implementing ecological fish stocking effectively suppressed algal growth to varying degrees and improved nitrogen and phosphorus levels. Lower water levels and ecological fish stocking had a significant impact on algal reproduction, while sediment reduction had a minimal effect. Conversely, lower water levels and ecological fish stocking did not significantly improve nitrogen and phosphorus concentrations in the reservoir, whereas sediment reduction had a noticeable effect. Consequently, the management strategies for the Shanzi Reservoir should prioritize external control measures and the implementation of ecological fish stocking.

Advancing interactive systems with liquid crystal network-based adaptive electronics.

Achieving adaptive behavior in artificial systems, analogous to living organisms, has been a long-standing goal in electronics and materials science. Efforts to integrate adaptive capabilities into synthetic electronics traditionally involved a typical architecture comprising of sensors, an external controller, and actuators constructed from multiple materials. However, challenges arise when attempting to unite these three components into a single entity capable of independently coping with dynamic environments. Here, we unveil an adaptive electronic unit based on a liquid crystal polymer that seamlessly incorporates sensing, signal processing, and actuating functionalities. The polymer forms a film that undergoes anisotropic deformations when exposed to a minor heat pulse generated by human touch. We integrate this property into an electric circuit to facilitate switching. We showcase the concept by creating an interactive system that features distributed information processing including feedback loops and enabling cascading signal transmission across multiple adaptive units. This system responds progressively, in a multi-layered cascade to a dynamic change in its environment. The incorporation of adaptive capabilities into a single piece of responsive material holds immense potential for expediting progress in next-generation flexible electronics, soft robotics, and swarm intelligence.

Photon-Dipole-Spin Interactions in M(TCNE)x/P(VDF-TrFE) Multiferroic Heterostructure Available for Bimodal Control of Multistate Data-Storage.

Organic multiferroic heterostructure is one of the most promising structures for the future design of high-density flexible energy-efficient data storage. Here, organic ferromagnetic metal(tetracyanoethylene) (M(TCNE))x/ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) multiferroic heterostructures are fabricated, where the excited state in M(TCNE)x interacted with localized dipole in P(VDF-TrFE) provides a key link for the interfacial coupling. Thus, aligned dipoles in P(VDF-TrFE) by external electric field can affect the magnetization of Fe(TCNE)x effectively to result in a pronounced magnetization-voltage (M-V) hysteresis loop. Moreover, light-induced electron-hole pairs in Fe(TCNE)x with long lifetime effectively interact with the dipoles in P(VDF-TrFE) to lead to an effect in external light control of electric polarization of P(VDF-TrFE). Overall, the organic multiferroic heterostructure provides the possibility of realizing two storage modes, light control of dipole as well as electric field control of spin, which can broaden multifunctional applications of organic multiferroic materials in the area of multistate storage.

Sensitivity Assessment of a Multiplex and Real-Time PCR Protocols for the Detection of Malaria in External Quality Control Samples in the Malaria Reference Center in Greece

Background: Accurate malaria diagnosis constitutes a challenging task, necessitating the need for the implementation of targeted and effective diagnostic tools. The purpose of the current study was to evaluate the effectiveness of two different molecular methodologies in terms of sensitivity for the detection of External Quality Assessment (EQA) Plasmodium samples. Methods: A total of 104 lyophilized blood samples from 14 different UK-NEQAS (National External Quality Assessment Site) (2016–2021) and eight WHO-NEQAS distributions (2017–2020) were analyzed. An in-house multiplex PCR protocol, followed by single target real-time PCR protocols for all five Plasmodium species, was implemented. Results: The multiplex PCR had a success rate of 10/16 and 20/28 for P. vivax and P. falciparum species, respectively. On the other hand, the respective results for real-time PCR had a success rate of 13/16 (P. vivax), 28/28 (P. falciparum), 5/8 (P. malariae), 8/10 (P. ovale), and 10/14 (P. knowlesi). Plasmodium falciparum samples displayed the highest sensitivity of detection, 0.02 parasites/μL. Plasmodium vivax samples displayed a 0.1 parasites/μL cutoff value, greater than the respective value for whole blood samples, while P. ovale species displayed a respective cutoff value of 0.05 parasites/μL. Due to the limited number of tested samples, data obtained for P. malariae and P. knowlesi species samples were inconclusive. Conclusions: Real-time PCR comprises a credible molecular methodology in terms of sensitivity assessment and detection of low parasitemia levels of Plasmodium sp. in EQA lyophilized blood samples.

Effectiveness of simulation-based clinical research curriculum for undergraduate medical students - a pre-post intervention study with external control

BackgroundSimulation is widely utilized in medical education. Exploring the effectiveness of high-fidelity simulation of clinical research within medical education may inform its integration into clinical research training curricula, finally cultivating physician-scientist development.MethodsStandard teaching scripts for both clinical trial and cross-sectional study simulation were designed. We recruited undergraduates majoring in clinical medicine at 3th grade into a pre-post intervention study. Additionally, a cross-sectional survey randomly selected medical undergraduates at 4th or 5th grade, medical students in master and doctor degree as external controls. Self-assessment scores of knowledge and practice were collected using a 5-point Likert scale. Changes in scores were tested by Wilcoxon signed-rank test and group comparisons were conducted by Dunn’s tests with multiple corrections. Multivariable quantile regressions were used to explore factors influencing the changes from baseline.ResultsSeventy-eight undergraduates involved the clinical trial simulation and reported improvement of 1.60 (95% CI, 1.48, 1.80, P < 0.001) in knowledge and 1.82 (95% CI, 1.64, 2.00, P < 0.001) in practice score. 83 undergraduates involved in the observational study simulation and reported improvement of 0.96 (95% CI, 0.79, 1.18, P < 0.001) in knowledge and 1.00 (95% CI, 0.79, 1.21, P < 0.001) in practice. All post-intervention scores were significantly higher than those of the three external control groups, P < 0.001. Higher agreement on the importance of clinical research were correlated with greater improvements in scores. Undergraduates in pre-post study showed high confidence in doing a future clinical research.ConclusionOur study provides evidence supporting the integration of simulation into clinical research curriculum for medical students. The importance of clinical research can be emphasized during training to enhance learning effect.

Perceptions of Chinese University English Majors on the Use of WeChat as a Platform for Peer Feedback in English Writing

Peer feedback is widely acknowledged as a valuable addition to English language learning, with several research confirming its various benefits in improving English writing skills (Liu &amp; Edwards, 2018). WeChat is the main communication tool in China, especially among young people. However, its potential for peer evaluation in English writing has not been thoroughly explored especially for English language learning, and more specifically for giving and receiving peer feedback for English writing. Current research mostly centers on Chinese college students, neglecting English majors who have comparable difficulties in mastering English writing abilities (Gan et al., 2004). Therefore, this study aims to investigate the perceptions of Chinese English majors on using WeChat for peer feedback. Data was gathered using a structured questionnaire that was designed based on the Technology Acceptance Model (TAM). The results show that most respondents have a good attitude towards using WeChat for peer feedback. Respondents have positive views on the platform's effectiveness in enabling peer feedback, along with factors like output quality, results demonstrability, and perceived ease of use. Participants also positively view aspects, such as external control, behavioral intention, voluntariness, and perceived enjoyment in using WeChat for peer feedback in English writing. Integrating WeChat as a peer feedback platform is considered beneficial for enhancing the teachinglearning process, which is important for educators and curriculum designers. The researchers posit that the use of WeChat as a platform can facilitate peer feedback for students’ English writing learning as a second language teaching tool as it shows the potential to improve the effectiveness of English education whilst also promoting the use of technology outside the classroom for peer feedback and interactive English language learning.

Case study in machine learning for predicting moderate pressure plasma behavior

Modeling and forecasting the dynamics of complex systems, such as moderate pressure capacitively coupled plasma (CCP) systems, remains a challenge due to the interactions of physical and chemical processes across multiple scales. Historically, optimization for a given application would be accomplished via a design of experiment (DOE) study across the various external control parameters. Machine learning (ML) techniques show the potential to “forecast” process conditions not tested in a traditional DOE study and thereby allow better optimization and control of a plasma tool. In this article, we have used standard DOE as well as ML predictions to analyze I-V data in a moderate-pressure CCP system. We have demonstrated that supervised regression ML techniques can be a useful tool for extrapolating data even when a plasma system is undergoing a transition in the heating mode, in this case from the alpha to gamma mode. Classification analysis of control parameters is another possible application of ML techniques that can be deployed for system control. Here, we show that given a large set of measured data, the models can identify the gas ratio in the feed gas as well as correctly identify the operating pressure and electrode gap in almost all the cases.

OILVEQ: an Italian external quality control scheme for cannabinoids analysis in galenic preparations of cannabis oil.

Italy legalized cannabis oil for specific medical conditions (neuropathic pain, refractory epilepsy and other established pathologies) in 2015, but mandates titration of principal cannabinoids before marketing each batch using iphenated techniques coupled with mass spectrometry. To assess reliability of laboratories from the Italian National Health Service in charge of titrating the batches, the Italian National Institute of Health set up an quality control program on determination of Δ9-tetrahydrocannabinol l (THC), cannabidiol (CBD), Δ9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA) in cannabis oil preparations. Two rounds of exercises have been carried out since 2019, involving sixteen Italian laboratories. Five different cannabis oil samples (19-1A and 19-1B for the first round and 22-1A, 22-1B and 22-1C for the second one were prepared and 1 mL amount of each sample was sent to the laboratories. The quantitative performance of each laboratory was assessed calculating the Z-score value, a statistical measurement for value's relationship to the mean of a group of values. In the first round, eight out of fourteen laboratories employed an LC-MS while the remaining six used GC-MS. Differently, in the second round, six out of eleven laboratories employed a GC-MS while the remaining five used LC-MS. In the first round, only 28.6 % laboratories achieved an acceptable performance (Z-score±2), and all of them used LC-MS as analytical method. In the second round, none of the laboratories achieved an acceptable performance. Satisfactory results, based on Z-scores, were generally low (0.0-75.0 %), with only one exception of 100 % for THCA-A determination in sample 22-1B. In the second round, three false negatives (two THC and one CBD by GC-MS determination) were reported while no false positives were described in the blank sample. The two rounds yielded a mean ERR% of 42 % approximately and a mean CV% around 70 % in GC-MS determination. When applying LC-MS determination, the two rounds yielded a mean ERR% of 36 % approximately and a mean CV% around 33 %. The obtained results underline the need for a clear and consistent protocol to be adopted by all laboratories intending to include the titration of oily cannabis-based products into their routinely analytical techniques. This emphasis on methodology standardization and participation to quality control schemes is essential for ensuring reliable and accurate measurements, ultimately enhancing the overall effectiveness and reliability of medical cannabis treatments.

Foreign experience of implementing ethical values in the anti-corruption policy of private and public sector organizations

The author analyzed and systematized the experience of foreign countries regarding the peculiarities of the implementation of ethical values in the anti-corruption policy of private and public sector organizations. Senior management when implementing anti­corruption standards, regardless of the form of ownership of the organization, when making management decisions, should be guided by their own ethical beliefs regarding their actions, display of integrity, ethics, influence on employees of lower management levels regarding the example of the prevalence of anti-corruption standards when making management decisions. The importance of the Codes of Ethics in encouraging the top management of the USA, EU, and Great Britain in the formation of organizational ethics and the reputation of international companies was established, and the strategic importance of leadership in the prevention of corruption in the formation of anti-corruption programs and the fight against corruption risks was determined in his work on leadership in the prevention of corruption. The experience of the USA, the EU, and Great Britain has shown that compliance with ethical behavior by the middle and lower ranks and, accordingly, the reduction of corruption risks, is mainly implemented taking into account the example set by the management in conducting the company's business. It has been found that the main ways of creating an ethical atmosphere are: establishment of values and principles of the organization, approval of Codes of Ethics, internal control, accountability, regular informing and holding of training events by the management with its mandatory participation regarding ethical values, trust in the management and its personal compliance on issues of corporate ethics in the absence of an ethics officer position. The practice of management implementation of ethical values in the anti-corruption policy of public authorities in Australia has shown that the ways of such implementation can be: the introduction of external control procedures open to the public, as well as confidential reporting procedures for senior management. The experience of Liberia, Kenya, and Georgia regarding leadership and corruption in the management of companies and in the public service as one of the main causes of civil wars is analyzed. Positive practices regarding the use of anti-corruption policy and the establishment of the role of leaders in the management of African countries have become the implementation of anti-corruption policy and strategy in the top management of countries, decentralization of power and the practice of identifying and returning illegally obtained funds of government officials to state accounts. The author summarizes effective ways of implementing ethical values in public sector organizations, using the example of Georgia, namely: political loyalty of management in the field of management in the fight against corruption; implementation of e-governance and e-services, long-term investments in building a corporate ethical culture, implementation of a mechanism for direct access to information on combating bribery to the company's top management, and encouraging employees to report suspicious activity related to corruption. Using the example of Estonia, the peculiarities of the role of management in overcoming corruption, the implementation of anti-corruption initiatives, certain trends regarding the role of the leadership of the law enforcement sphere in anti-corruption policy have been established. Estonian legislation has formed trends regarding the identification of the role of management in the formation of anti­corruption culture in law enforcement agencies through organizational views on corruption and the views of managers on overcoming corruption, in particular: the openness of top management to discussing anti-corruption issues in relation to their own organizations; focus on the organizational culture of non-perception of corruption starting from the top management level; integration into everyday practice of existing ethical standards; prevention of corruption risks associated with senior officials of organizations.

A Review on Design and Fabrication of Mechanically Operated Gate System

Entryways have become increasingly common in private settings, serving as entrances to enclosed spaces or gaps in fences to regulate passage. Nowadays, many entry gates are operated by automated systems, boasting various advanced features. The demand for automated or mechanically operated doors has been steadily rising. The described automatic gate system is designed to automate entrances to parking lots of residential properties, businesses, and public car parks. It utilizes a mechanically controlled mechanism comprising a base plate connected to an L-shaped rod, which is in turn attached to a pulley fixed on the gate's main body. This setup enables the gate to be raised by spinning the pulley, and it gradually descends with the assistance of a car boot shock absorber when the vehicle's load is removed. This system ensures continuous gate opening and closing without the need for an external power source. While operating the gate manually reduces the burden on individuals, it is designed to function automatically through mechanical movements without requiring external control. Keywords: Mechanical Operated Gate, Pulley, Base plate, Boot shock

Statistical methods to control for confounders in rare disease settings that use external control

ABSTRACT In the drug development for rare disease, the number of treated subjects in the clinical trial is often very small, whereas the number of external controls can be relatively large. There is no clear guidance on choosing an appropriate statistical method to control baseline confounding in this situation. To fill this gap, we conduct extensive simulations to evaluate the performance of commonly used matching and weighting methods as well as the more recently developed targeted maximum likelihood estimation (TMLE) and cardinality matching in small sample settings, mimicking the motivating data from a pediatric rare disease. Among the methods examined, the performance of coarsened exact matching (CEM) and TMLE are relatively robust under various model specifications. CEM is only feasible when the number of controls far exceeds the number of treated, whereas TMLE has better performance with less extreme treatment allocation ratios. Our simulations suggest bootstrap is useful for variance estimation in small samples after matching.