Clearance Process Research Articles

The elephant in the room of EU copyright originality: Time to unpack and harmonize the essential requirement of copyright

AbstractThe dividing line between the artistic and literary heritage privatized by copyright and the public domain depends on just one word which is completely alien to the traditional legal jargon: originality. As if it were not enough the essential requirement of copyright is highly polysemic, being its meaning also sensitive to the specific temporal and geographical context. For instance, the same interior design for make‐up stores has been reputed original in Italy but not in France and Portugal. The European legislator has deeply regulated several aspects of copyright, but paradoxically it is laconic on the fundamental element triggering the exclusive right: a work is original if it reflects the author's own intellectual creation. Although the CJEU played a pivotal role in filling this gap through a string of decisions, national judges are still uncertain on the relevant factors for the originality assessment, as witnessed by three new references for preliminary rulings. The different approaches to the originality requirement could be problematic for the well‐functioning of the artistic and cultural markets considering the potential heterogeneous legal status of the same creation, which might be under copyright protection in one Member State while in the public domain in another one. This could prejudice rights clearance processes, including the latest one regarding text and data mining for machine learning purposes advocated by a line of scholars. By elaborating on settled European and national case‐law, this paper extracts some metrics for ensuring legal certainty on the interpretation of the originality requirement. These coordinates could be incorporated in a wider European intervention harmonizing copyright law, keen to the Wittem Group project. Finally, it argues that the idea of introducing copyright formalities would also ensure more legal certainty on the status of intellectual works since the computational analysis of voluntary registrations could become a useful tool for predicting the originality of future works.

Association Between Blood Pressure Variation During Dialysis and Cardio-Cerebrovascular Events.

In hemodialysis patients, blood pressure variability (BPV) is associated with cardiovascular events and all-cause mortality. However, previous research has predominantly concentrated on the predialysis BPV. In contrast, intradialytic BPV, reflecting the cardiovascular regulatory function during the process of rapid clearance of volume overload, holds greater relevance to the prognosis of patients. In this study, a latent category trajectory model was used to identify the patterns of intradialytic BPV and analyze the association between intradialytic BPV and the cardio-cerebrovascular events and other clinical outcomes. We found the variation of intradialytic systolic blood pressure (SBP) was associated with the risk of cardio-cerebrovascular events in hemodialysis patients. Patients in "SBP Class 4" and "SBP Class 3" subgroups were associated with the occurrence of cardio-cerebrovascular events and the number of cardio-cerebrovascular event hospitalizations during the follow-up period. This indicates that the variation pattern of intradialytic SBP results from the comprehensive action of various BP regulatory mechanisms in the body, which can reflect the level of cardiovascular regulatory function in hemodialysis patients and serve as a predictor of recent adverse cardio-cerebrovascular events.

The Determinants of Customs Duties Evasion in Egypt

Abstract Following the Arab Spring in 2011, Egypt implemented policies to restrict imports to control foreign currency spending, as foreign currency reserves dwindled. This decline was driven by reduced tourism revenues and remittances from Egyptians abroad. Among the measures Egypt adopted were floating the local currency, raising the customs exchange rate (used to calculate customs duties), and increasing tariff rates on numerous goods. These actions significantly raised the cost of imports, potentially incentivizing importers to evade customs duties. This study aims to explore the determinants of customs duties evasion in Egypt using a time series econometric model. Key variables analyzed include tariff rates, customs clearance efficiency, corruption, trade openness, and non-tariff barriers (NTBs). The analysis covers the period from 2001 to 2023. Regression analysis and econometric tests were conducted to validate the results. Findings suggest that customs clearance processes, tariff policies, corruption, trade openness, and NTBs significantly influence customs duties evasion in Egypt

The Impact of Free Trade Zones on the International Competitiveness of Cross-Border E-Commerce Companies

As international e-commerce expands so quickly, cross-border e-commerce (CBEC) is becoming more and more important to China's exports. This study attempts to investigate the effect of free trade zones (FTZs) on the global competitiveness based on the FTZ. A thorough analysis of the ideas surrounding FTZs and CBEC allows for the clarification of the fundamental research framework and the application of both qualitative and quantitative research methods. The development strategy of CBEC is finally presented. After a review of the advantages of FTZ policies (such as expediting the customs clearance process, lowering trade barriers, improving logistics efficiency, etc.) and the disadvantages of CBEC policies (such as increasing market competition, diversifying the international market), and unpredictable regulatory policies: formulate and improve the relevant policies, strengthen the construction of the CBEC service platform, expand the scope of the CBEC comprehensive pilot zone, improve the financial service system, and cultivate the interdisciplinary talents needed for CBEC.

Optimal Dosing Recommendations of Clonidine in Pediatrics Using Physiologically Based Pharmacokinetic Modeling.

Clonidine has been widely used in the pediatric population to treat neonatal abstinence syndrome (NAS), attention deficit hyperactivity disorder (ADHD), sedation, and Tourette's syndrome; however, there is no consensus on dosing. This research aims to recommend optimal dosing of clonidine in the pediatric population using physiologically based pharmacokinetic (PBPK) modeling. The pediatric PBPK model was developed from an adult model by scaling the clearance processes from adults to pediatrics using ontogeny equations. The adult and pediatric models were verified using clinical PK data, and the model performance was evaluated based on visual predictive checks and absolute fold error (AFE). The final pediatric PBPK model was used to simulate clonidine PK in the virtual pediatric population. The optimal dose was recommended based on a target concentration representing clonidine's α-2 central agonist activity (EC50 = 40.5 nM). The adult and pediatric models predicted well, with more than 90% of observed data captured within the 95% prediction interval of simulated data. The AFE values were within 2-fold for clonidine plasma concentrations from observed and predicted data. The pediatric simulations showed that 30 µg/kg dose orally for neonates and 0.9 mg/day orally for children (6-17 years) are optimal for achieving target concentrations for maximal α-2 adrenergic activity. The pediatric PBPK model of clonidine scaled from the adult PBPK model provided optimal dosing recommendations for clonidine in different pediatric age groups. The pediatric PBPK model described in this study can be extended to other pediatric age groups and routes of administration.

Breaking down barriers and building bridges: Social outreach and engagement in audio-visual heritage at the National Library of Scotland’s Moving Image Archive

Social outreach and engagement in UK-based audio-visual archives are under-researched areas worthy of further investigation, particularly considering the naturally immersive quality of audio-visual content and its potential to draw in, educate and engage audiences. This qualitative study explores three interconnected foci: challenges and opportunities currently faced by the National Library of Scotland’s Moving Image Archive with regards to preserving and making publicly accessible born-digital and analogue audio-visual materials; the impact of these challenges and opportunities upon the Moving Image Archive’s levels of social outreach and engagement; and ways to elevate the Moving Image Archive’s social outreach and engagement. Our findings indicate that, from a National Library of Scotland’s staff perspective, addressing issues related to copyright law and rights clearance processes, as well as supporting engagement in local areas and providing educational programmes on caring for materials, would be beneficial in increasing social outreach and engagement. The research findings informed recommendations, including increased staff resource and dedicated training in rights clearance processes, extending outreach and engagement beyond Scotland’s central belt, addressing the physical limitations of the archive’s public space and promoting the usability and creative re-use of archival material, as well as addressing gaps within the collection. Recommendations based on this study may contribute to further aligning the needs of the Moving Image Archive with the National Library of Scotland’s Reaching People: Library Strategy 2020–2025.

Integration of the bulk transcriptome and single-cell transcriptome reveals efferocytosis features in lung adenocarcinoma prognosis and immunotherapy by combining deep learning

BackgroundEfferocytosis (ER) refers to the process of phagocytic clearance of programmed dead cells, and studies have shown that it is closely related to tumor immune escape.MethodsThis study was based on a comprehensive analysis of TCGA, GEO and CTRP databases. ER-related genes were collected from previous literature, univariate Cox regression was performed and consistent clustering was performed to categorize lung adenocarcinoma (LUAD) patients into two subgroups. Lasso regression and multivariate Cox regression analyses were used to construct ER-related prognostic features, and multiple immune infiltration algorithms were used to assess the correlation between the extracellular burial-related risk score (ERGRS) and tumor microenvironment (TME). And the key gene HAVCR1 was identified by deep learning, etc. Finally, pan-cancer analysis of the key genes was performed and in vitro experiments were conducted to verify the promotional effect of HAVCR1 on LUAD progression.ResultsA total of 33 ER-related genes associated with the prognosis of LUAD were identified, and the prognostic signature of ERGRS was successfully constructed to predict the overall survival (OS) and treatment response of LUAD patients. The high-risk group was highly enriched in some oncogenic pathways, while the low-ERGRS group was highly enriched in some immune-related pathways. In addition, the high ERGRS group had higher TMB, TNB and TIDE scores and lower immune scores. The low-risk group had better immunotherapeutic response and less likelihood of immune escape. Drug sensitivity analysis revealed that BRD-K92856060, monensin and hexaminolevulinate may be potential therapeutic agents for the high-risk group. And ERGRS was validated in several cohorts. In addition, HAVCR1 is one of the key genes, and knockdown of HAVCR1 in vitro significantly reduced the proliferation, migration and invasion ability of lung adenocarcinoma cells.ConclusionOur study developed a novel prognostic signature of efferocytosis-related genes. This prognostic signature accurately predicted survival prognosis as well as treatment outcome in LUAD patients and explored the role of HAVCR1 in lung adenocarcinoma progression.

Drug-induced cholestasis (DIC) predictions based on in vitro inhibition of major bile acid clearance mechanisms.

Drug-induced cholestasis (DIC) is recognized as a major safety concern in drug development, as it represents one of the three types of drug-induced liver injury (DILI). Cholestasis is characterized by the disruption of bile flow, leading to intrahepatic accumulation of toxic bile acids. Bile acid regulation is a multifarious process, orchestrated by several hepatic mechanisms, namely sinusoidal uptake and efflux, canalicular secretion and intracellular metabolism. In the present study, we developed a prediction model of DIC using in vitro inhibition data for 47 marketed drugs on nine transporters and five enzymes known to regulate bile acid homeostasis. The resulting model was able to distinguish between drugs with or without DILI concern (p-value = 0.039) and demonstrated a satisfactory predictive performance, with the area under the precision-recall curve (PR AUC) measured at 0.91. Furthermore, we simplified the model considering only two processes, namely reversible inhibition of OATP1B1 and time-dependent inhibition of CYP3A4, which provided an enhanced performance (PR AUC = 0.95). Our study supports literature findings suggesting a contribution not only from a single process inhibition, but a rather synergistic effect of the key bile acid clearance processes in the development of cholestasis. The use of a quantitative model in the preclinical investigations of DIC is expected to reduce attrition rate in advanced development programs and guide the discovery and development of safe medicines.

Lower DTI-ALPS index in patients with major depressive disorder: Correlation with fatigue

Background and purposeDiffusion tensor imaging along perivascular spaces (DTI-ALPS) is an index that may provide insights into intracranial waste clearance processes. Glymphatic system dysfunction has been suggested to play a role in the development of major depressive disorder (MDD). Additionally, fatigue—a common precursor of MDD—is also closely connected to the waste clearance function of the central nervous system (CNS), further underscoring the significance of efficient waste removal in MDD. However, evidence linking altered DTI-ALPS index to MDD remains limited. This study aims to investigate the changes in the DTI-ALPS index in patients with MDD and explore the potential interplay between DTI-ALPS index alterations, fatigue, and the presence of MDD. Material and methodsA total of 46 patients with MDD and 55 healthy controls (HC) were included in the study. All participants underwent diffusion tensor imaging using the same 3-T MRI (3-Tesla Magnetic Resonance Imaging) scanner. The DTI-ALPS index was assessed, and the Chalder Fatigue Scale (CFS) was used to evaluate fatigue levels in both groups, and the 17-item Hamilton Depression Rating Scale (HAMD-17) was used to evaluate the severity of depression in the patients. We compared the DTI-ALPS index and clinical characteristics between the MDD and HC group, and explored the relationship among the DTI-ALPS index, CFS scores, and the presence of MDD through mediation analysis. ResultsThe DTI-ALPS index in the right hemisphere (DTI-ALPS-R) is significantly lower in patients with MDD (t = 2.41, P = 0.02). The MDD patients exhibited significantly higher scores on the CFS scales compared with HCs (t = 13.12, P <.001). Mediation analysis showed that the CFS score plays a significant mediating role between DTI-ALPS-R and the presence of MDD, acting as a full mediator (indirect effect β = −0.230, 95 % CI: [-0.388, −0.059]). ConclusionOur study found that patients with MDD have a reduced DTI-ALPS index. This reduction appears to contribute to the development of MDD by facilitating the accumulation of fatigue symptoms. These findings may provide a new perspective on the pathogenesis of MDD, suggest a potential new biomarker for MDD, and offer new insights for its treatment.

Patient visit behaviour shapes the virus infection dynamics in hosts

Chronic HBV infection is a dynamic process of rapid viral replication and clearance, with large amounts of virus being produced and lost in the body daily. The patient's visit behaviour is closely related to viral load in the body, while the data-driven mathematical model still lacking. Therefore, we first include 28,912 patients to investigate the relationships between the visit behaviour and the HBV-DNA virus load. Then, we propose an HBV virus infection dynamics model that considers the patient's visit behaviour. The system is chaotic once the behaviour of patients during visits depends on the virus load. Our results may help us understand the process of viral transmission, and increasing the visit probability to the clinic can lead to stabilising HBV-DNA viral loads and further help healthcare professionals develop targeted clinical intervention strategies.

The Effect of Service Quality And Agency Skills on The Effectiveness of Sailing Time at Bulk Cargo Carrier

The length of the ship clearance process at an agency company makes a reference for each company in improving the quality of services provided and the skills of its employees. This study aims to determine the effect of service quality and skills on the effectiveness of sailing time for bulk cargo ships loaded with coal at three different agency companies on the island of Kalimantan. The method used is a quantitative approach through primary data processing on IBM SPSS (Statistical Package for the Social Science) 25 which comes from 30 respondents. The results of the research proven through the t test show that service quality and skills partially have a positive and significant influence on effectiveness. Simultaneous testing with an Fcount value of 33.755&gt; 4.20 and a sig value of 0.000 &lt;0.05 proves that service quality and skills together have a significant influence on effectiveness. This is supported by the coefficient of determination test which states that the service quality and skills variables have an influence of 71.4%, on the effectiveness variable, while 28.6% of effectiveness is influenced by variables outside of service quality and skills not examined by the author. The conclusion in this study is that the service quality and skills variables have a positive influence on the effectiveness variable partially and simultaneously.

Modernizing Medical Device Regulation: Challenges and Opportunities for the 510(k) Clearance Process.

Nearly all medical devices reviewed by the U.S. Food and Drug Administration (FDA) are authorized via the 510(k) clearance process. Established in 1976, this review pathway bases authorizations on the comparability of new devices to previously authorized devices ("predicates"). This evaluation usually does not require clinical evidence of safety and effectiveness. Advocates of the 510(k) clearance process tout its support for device innovation and rapid market access, and critics of the 510(k) clearance process express that it may inadequately protect patient safety. In September 2023, the FDA issued 3 guidance documents that, if finalized, would significantly change medical device regulation. This article provides clinical and regulatory context for the proposed guidance documents, which focus on predicate selection, clinical testing requirements, and implantable devices, and identifies opportunities for further reforms that promote transparency and patient safety.

The Role Of Agency Services In Serving Clearance In And Out Of Ship With Manual System at PT. Bama Putra Sukses Bogor

Shipping companies have an important role in providing services to ships visiting a port. Shipping companies appointed as agents are the parties that will be responsible for taking care of everything so that the ships they represent can dock properly, on time, and smoothly in carrying out their activities at the port. Ship agency services are needed to assist the process of clearance in and out of ships at a port in order to create conducive ship activities. This study was conducted to determine the role of agencies in serving the clearance in and out process and the factors that hinder the ship clearance process using a manual system at PT. Bama Putra Sukses Bogor. This study uses a qualitative approach with a descriptive type. Data collection for this study was carried out using observation, interview, and documentation techniques. The results of this study showed that the role of agencies in serving ship clearance in and out with a manual system at PT. Bama Putra Sukses Bogor is a series of ship clearance processes from ship entry to ship exit. Agents play a role in providing their services to ship owners in ship clearance services that are oriented towards managing ship documents in order to facilitate the loading and unloading process. Factors that hinder the clearance in and out process at PT. Bama Putra Sukses consist of expired documents and problems waiting for the destination port or called waiting next port.

Issues Relating to the Identification and Customs Examination of Internationally Traded Goods in Uzbekistan

The process of organising customs control of foreign trade operations in the context of an ongoing global pandemic and the urgent need to provide food is an important one. Here, we analyse the methodology of non-tariff regulation of foreign economic activity and the interaction between the authorised bodies of Uzbekistan state administrations in this process. The role and place of customs examination in the process of certification of foreign trade goods is explored, including the participation of customs experts from the Central Customs Laboratory. This paper outlines the issues involved in the overall customs clearance process as it relates to the identification of controlled goods, and identifies areas for improvement.

Regulatory requirements for the approval of anti-cancer drugs as per CDSCO in India comparison with Singapore

This study examines the regulatory requirements for anticancer medications in Singapore and India are compared in this abstract. It draws attention to the frameworks set up by Singapore's Health Sciences Authority (HSA) and India's Central Drugs Standard Control Organization (CDSCO). The procedures for clinical studies, approval schedules, and post-marketing surveillance are among the main distinctions. Singapore places a strong emphasis on strict safety and efficacy criteria, whereas India stresses a quicker clearance process to address pressing healthcare needs. The investigation highlights how various regulatory methods affect patient access, innovation, and medicine supply in both nations. Recent decades have seen extraordinary improvements in the discovery of anticancer medications, transforming both cancer treatment and patient outcomes. With an emphasis on the main areas of anticancer therapeutics—chemotherapy, targeted therapy, immunotherapy, and hormone therapy—this study offers a thorough summary of the state of the field. We examine each drug class's methods of action, effectiveness, and difficulties while showcasing more recent developments like immune checkpoint inhibitors and CAR-T cell therapy. We also go over side effects, drug resistance, and how tailored medicine might improve the effectiveness of treatment. A look is also given to new developments in drug research, such as the application of nanotechnology and AI-driven drug discovery. The review attempts to shed light on the changing tactics used to fight cancer and the potential paths for anticancer medication development.

Assessing Autophagy Flux in Glioblastoma Temozolomide Resistant Cells.

Autophagy is a critical cellular process involved in the degradation and recycling of cytoplasmic components, playing a dual role in cancer by either promoting cell survival or facilitating cell death. In glioblastoma (GB), autophagy has been implicated in resistance to the chemotherapeutic agent temozolomide (TMZ). This study presents a novel method to accurately measure autophagy flux in TMZ-resistant glioblastoma cells, combining advanced imaging techniques with biochemical assays. By quantifying key autophagy markers such as LC3-II and SQSTM1, our approach provides detailed insights into the dynamic processes of autophagosome formation and clearance under therapeutic stress. This method advances our understanding of autophagy in GB chemoresistance and has significant implications for the development of autophagy-targeted therapies. The ability to monitor and manipulate autophagy flux in real time offers a promising avenue for monitoring and understanding TMZ resistance and improving patient outcomes in glioblastoma treatment.

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

The spleen constantly clears altered red blood cells (RBCs) from the circulation, tuning the balance between RBC formation (erythropoiesis) and removal. The retention and elimination of RBCs occur predominantly in the open circulation of the spleen, where RBCs must cross submicron-wide inter-endothelial slits (IES). Several experimental and computational studies have illustrated the role of IES in filtrating the biomechanically and morphologically altered RBCs based on a rigid wall assumption. However, these studies also reported that when the size of IES is close to the lower end of clinically observed sizes (less than 0.5 μm), an unphysiologically large pressure difference across the IES is required to drive the passage of normal RBCs, sparking debates on the feasibility of the rigid wall assumption. In this work, We propose two deformable IES models, namely the passive model and the active model, aiming to explore the impact of the deformability of IES on the filtration function of the spleen. In the passive model, we implement the worm-like string model to depict the IES’s deformation as it interacts with blood plasma and allows RBC to traverse. In contrast, the active model involved regulating the IES deformation based on the local pressure surrounding the slit. To demonstrate the validity of the deformable model, we simulate the filtration of RBCs with varied size and stiffness by IES under three scenarios: (1) a single RBC traversing a single slit; (2) a suspension of RBCs traversing an array of slits, mimicking in vitro spleen-on-a-chip experiments; (3) RBC suspension passing through the 3D spleen filtration unit known as’the splenon’. Our simulation results of RBC passing through a single slit show that the deformable IES model offers more accurate predictions of the critical cell surface area to volume ratio that dictate the removal of aged RBCs from circulation compared to prior rigid-wall models. Our biophysical models of the spleen-on-a-chip indicate a hierarchy of filtration function stringency: rigid model > passive model > active model, providing a possible explanation of the filtration function of IES. We also illustrate that the biophysical model of ‘the splenon’ enables us to replicate the ex vivo experiments involving spleen filtration of malaria-infected RBCs. Taken together, our simulation findings indicate that the deformable IES model could serve as a mesoscopic representation of spleen filtration function closer to physiological reality, addressing questions beyond the scope of current experimental and computational models and enhancing our understanding of the fundamental flow dynamics and mechanical clearance processes within in the human spleen.

Sustainable Development of the China Railway Express under the Belt and Road Initiative: Focusing on Infrastructure Reliability and Trade Facilitation

The China Railway Express (CR Express) is an important component of the Belt and Road Initiative (BRI). The sustainable development of CR Express provides critical support for regional economic integration and promotes a balanced development of the supply chain. Infrastructure reliability and trade facilitation greatly impact the operation of CR Express and are crucial for improving the competitiveness of transnational trade and cross-border efficiency. Inconsistent transportation infrastructure standards and low-efficient transportation service procedures affect the cross-border movement of cargo among countries. This paper integrates quantified metrics of infrastructure reliability and trade facilitation into a spatial friction model based on the electrical resistance theory, estimating the impact of these factors on the transportation flow of CR Express. Additionally, three scenarios of infrastructure reliability and trade facilitation are established for the four trade routes from Zhengzhou to Hamburg. Numerical experiments show that compared with inland river routes and traditional ocean routes, infrastructure reliability and trade facilitation significantly influence the transport flow of CR Express. These research results can provide a reference for the improvements of CR Express transportation efficiency and the simplification of customs clearance processes, potentially promoting the sustainable development of the CR Express supply chain to some extent.

Respond to Public Health Emergencies and The Law Preparedness Challenges and Solutions

Laws are a very powerful tool for defending human rights. These could be parliamentary enactments, local panchayat regulations, international conventions, or constitutions. Every facet of the emergency and public health response is based on law and policy. Laws made it possible to establish lockdowns, declare states of emergency, and, more recently, speed the clearance process for vaccines. The removal of antiquated laws, regulations, and backup plans frequently revealed them to be insufficient or out-of-date, necessitating the quick creation of new legislation. Never before have so many laws concerning one incident been passed in so many nations in such a short period of time. Communities are kept safe and lives are saved by domestic legal preparedness for catastrophes, which includes public health emergencies. The cornerstones of disaster risk management are law and policy, which establish guidelines for the who, what, and when of emergency response operations. When preparedness and response efforts lack a solid legal foundation, they may be disorganised and ineffectual, which frequently causes the most vulnerable individuals to wait longer for critical assistance. This essay suggests that there is a general deficiency of robust public health emergency legislation as well as a lack of legal readiness for such situations.

The Rate of Corruption in Local Municipalities Harshly Offsets Revenue Enhancement Strategies on Property Clearances and Transfers of Properties: A Case of Ba-Phalaborwa Local Municipality

Corruption within local municipalities remains a significant obstacle to economic development and public trust, particularly in the context of property clearances and transfers. This study examines the extent to which corruption within the Ba-Phalaborwa Local Municipality undermines revenue enhancement strategies designed to streamline property clearances and transfers. By employing a mixed-methods approach, this research highlights the discrepancies between policy intentions and actual practices. The findings suggest that corruption significantly hampers the effectiveness of these revenue enhancement strategies, leading to inefficiencies and public dissatisfaction. The study draws on primary data collected from municipal employees, property owners, and real estate professionals. Interviews and surveys reveal a pervasive culture of bribery and nepotism that undermines formal procedures. Additionally, an analysis of municipal records uncovers irregularities in property clearance and transfer processes, suggesting systemic issues that require urgent attention. Addressing corruption in the Ba-Phalaborwa Local Municipality is crucial for restoring public trust and enhancing revenue from property transactions. The study proposes several policy recommendations, including stricter enforcement of anti-corruption measures, enhanced transparency, and improved accountability mechanisms. These strategies are essential for ensuring that property clearances and transfers are conducted fairly and efficiently, ultimately benefiting the local economy and community.