Unregulated Channels Research Articles

Materijalno krivično pravo Medicrime konvencije i krivično zakonodavstvo Bosne i Hercegovine - odnos sklada i nesklada

The trade in counterfeit medical products is a growing global crime industry (especially in the domain of organized crime), which represents a big threat to natural persons, i.e., patients, but also to healthcare systems. The circulation and sale of counterfeit medical products takes place through unregulated channels (on the side of the road, in a marketplace, online, or even in bars, nightclubs or bakeries). The Convention of the Council of Europe on counterfeit medical products and other illegal acts that include threats to public health represents the first international agreement of that kind, that is, an international instrument that establishes a legal framework for the fight against this criminal black market. It criminalizes certain actions, prescribes certain provisions related to the criminal justice procedure, protects the rights of victims and improves national and international cooperation in criminal justice matters.

Cyber Defense in the Age of Artificial Intelligence and Machine Learning for Financial Fraud Detection Application

Cyber security comes with a combination of various security policies, AI techniques, network technologies that work together to protect various computing resources like computing networks, intelligent programs, and sensitive data from attacks. Nowadays, the shift to digital freedom had led to opened many new challenges for financial services. Cybercriminals have found the ability to leverage e- currency exchanges and other financial transactions to perform their fraudulent activities. The unregulated channel makes it essential for banks and financial institutions to deploy advanced AI & ML (DL) techniques to fight cybercrime. This can be implemented by deploying AI & ML (DL) techniques. Customers are experiencing an increase in the fraud-hit rate in financial banking operations. It is difficult to defend against dynamic cyber-attacks using conventional non- dynamic algorithms. Therefore, AI with machine learning techniques has been set up with cyber security to build intelligent models for malware categorization & intelligently sensing the fraught with danger. This paper introduces the cyber security defense mechanism by using artificial intelligence (AI), machine learning (ML)) techniques with the current Feedzai security model to identifying fraudulent banking transaction. We have given a preface to the popular ML & AI model with random forest algorithm and Feedzai’s Open ML fraud detection software tool, which provides automatic fraud-recognition to the current intelligent framework for solving Financial Fraud Detection.

P-738 Impact of limited reproductive health awareness on PCOS diagnosis timelines and the need for improved patient education

Abstract Study question Does the lack of awareness of Polycystic ovary syndrome (PCOS) symptoms contribute to a delay in diagnosis? Summary answer Limited awareness regarding reproductive health symptoms can negatively impact help-seeking behaviour, delaying diagnostic timelines. What is known already PCOS is a common endocrine condition estimated to affect up to 20% of women worldwide. Frequently observed symptoms include oligomenorrhea or amenorrhea, clinical features of hyperandrogenism, metabolic dysfunction, infertility and poor mental health. Despite its prevalence and the debilitating impact of symptoms on quality of life, it takes an average of two years and over three clinical consultations to diagnose. Delayed diagnosis may be influenced by a lack of standardised screening guidelines, poor understanding of how PCOS manifests in ethnic minorities and hesitancy from the general public to seek help for their reproductive health symptoms. Study design, size, duration A cross-sectional study investigating the barriers to diagnosis of PCOS. Participants aged 18 or older with an existing or suspected diagnosis of PCOS were invited to complete an online survey across five days in January 2022. The survey assessed general demographic information, the influence of symptoms on their daily life and their experiences with receiving a diagnosis. Of the 200 responses, 143 responses were analysed and 99 were included in the results. Participants/materials, setting, methods Participants were aged between 18 - 45 and provided informed consent after reading a patient information leaflet detailing the background of the study. 75 (52.44%) participants were UK-based, while 68 (47.55%) were based abroad. Ethical approval of all study-related documents was given by the Hertility Health Research Ethics Committee. The online survey was presented on Typeform and disseminated via the social media platforms Instagram, Twitter and LinkedIn. Descriptive statistics are presented. Main results and the role of chance Of the 143 participants, 99 (69.2%) reported a PCOS diagnosis. Anxiety (71.4%), irregular menstrual cycles (69.4%) and weight-related concerns (64.3%) were the most commonly reported symptoms. Despite the majority reporting that their symptoms impacted daily life (80.8%), mental health (82.8%), and educational or work performance (70.7%), only 10.2% had sought medical help immediately while 75.5% waited for up to 2 years. Not realising their symptoms required medical help (73.2%), lack of information regarding routes to care (18.3%) and stigma from family members (18.3%) were the most common reasons why medical help was not sought immediately. Following clinical consultations, 54.7% of participants were not satisfied with the information provided to manage their diagnosis. Although mental health-related symptoms were most frequently reported (75.5%), only 4.8% reported that management strategies for mental health were referenced in their consultations. Of the 93.2% of those looking for extra information online, only 52.3% used official websites such as the National Health Service (NHS) website. Many participants also chose to use social media sources such as Instagram and Tik Tok for information (52.3%) and support (59.3%). Limitations, reasons for caution Although there was a global uptake, the study needs to be carried out on a larger scale with an emphasis on minority ethnicities. Recall bias could have also impacted findings as the participants were required to provide details on their entire diagnosis experience. Wider implications of the findings It is evident that limited awareness regarding reproductive health can delay the diagnosis of PCOS. Due to unsatisfactory management by healthcare providers, patients heavily rely on unregulated channels such as social media to obtain reproductive health information, highlighting the need for better Sex and Fertility Education programs and improved accessibility. Trial registration number NA

Challenges in maintaining medicine quality while aiming for universal health coverage: a qualitative analysis from Indonesia

IntroductionIndonesia, the world’s fourth most populous nation, is close to achieving universal health coverage (UHC). A widely-publicised falsified vaccine case in 2016, coupled with a significant financial deficit in the...

Weedy activism: women, plants, and the genetic pollution of urban Japan

Along the ports of Japan, civilians have made a peculiar discovery: in a country where genetically modified (GM) crop cultivation is prohibited, wild canola weeds flourishing in the cracks of sidewalks are exhibiting the GM trait of herbicide resistance to Monsanto's infamous glyphosate. Able to enter the archipelagic country via unregulated channels and to cross-pollinate with locally grown crops, the weeds threaten to make inroads into the food system in ways unbeknownst to human actors. Among the most vocal of groups responding to this urban ecological threat are Japanese women and mothers involved in consumer co-operative systems. This article documents the emergence of their activism to demonstrate how situated and transformative political action is key to the political ecological study of human-plant encounters. It does so by interrogating the notion of weedyactivism as a way to see plants not only as the object of political action, but also as a conceptual heuristic for understanding the kinds of political subjects that emerge in interaction with local environments.

Wetland birds of middle Vistula River during breeding season: the impact of human activities on the distribution, abundance and richness of species

Wetland birds of middle Vistula River during breeding season: the impact of human activities on the distribution, abundance and richness of species

Policing the Organizational Threat in Morocco: Protest and Public Violence in Liberal Autocracies

AbstractAs a prominent form of state violence against civilians, protest policing represents the type of coercion that “liberal” autocrats seek to minimize. Departing from aggregate notions of “mass threat” that dominate studies of authoritarian response to contention, this article develops an event‐level model of protest policing centering the role of social movement organizations in shaping elite threat perceptions and, hence, the likelihood that protests will face state violence. More than public protest per se, I argue that liberal autocrats fear the rise of autonomous, national‐level organizations capable of providing unregulated channels for citizen claim‐making. Having forsworn the ability to control which networks become active as social movement organizations, liberal autocrats use protest policing to dissuade citizens from mobilizing with autonomous organizations and to protect the near‐monopoly of embedded organizations over contention. I illustrate these arguments with unique protest event data from Morocco. I draw implications for the durability of liberalized regimes.

Impact of the Tobacco Products Directive on self-reported exposure to e-cigarette advertising, promotion and sponsorship in smokers-findings from the EUREST-PLUS ITC Europe Surveys.

Advertising, promotion and sponsorship of electronic cigarettes (ECAPS) have increased in recent years. Since May 2016, the Tobacco Products Directive 2014/40/EU (TPD2) prohibits ECAPS in various advertising channels, including media that have cross-border effects. The objective of this study was to investigate changes in exposure to ECAPS in a cohort of smokers from six European Union member states after implementation of TPD2. Self-reported exposure to ECAPS overall and in various media and localities was examined over two International Tobacco Control Policy Evaluation survey waves (2016 and 2018) in a cohort of 6011 adult smokers from Germany, Greece, Hungary, Poland, Romania and Spain (EUREST-PLUS Project) using longitudinal generalized estimating equations models. Self-reported ECAPS exposure at both timepoints varied between countries and across examined advertising channels. Overall, there was a significant increase in ECAPS exposure [adjusted odds ratio (aOR): 1.25, 95% CI: 1.09-1.44]. Between waves, no consistent patterns of change in ECAPS exposure across countries and different media were observed. Generally, ECAPS exposure tended to decline in some channels regulated by TPD2, particularly on television and radio, while exposure tended to increase in some unregulated channels, such as at points of sale. The findings suggest that the TPD2 was generally effective in reducing ECAPS in regulated channels. Nonetheless, further research is warranted to evaluate its role in reducing ECAPS exposure, possibly by triangulation with additional sources of data.

Probing ion channel activity of human islet amyloid polypeptide (amylin)

Interactions of human islet amyloid polypeptide (hIAPP or amylin) with the cell membrane are correlated with the dysfunction and death of pancreatic islet β-cells in type II diabetes. Formation of receptor-independent channels by hIAPP in the membrane is regarded as one of the membrane-damaging mechanisms that induce ion homeostasis and toxicity in islet β-cells. Here, we investigate the dynamic structure, ion conductivity, and membrane interactions of hIAPP channels in the DOPC bilayer using molecular modeling and molecular dynamics simulations. We use the NMR-derived β-strand-turn-β-strand motif as a building block to computationally construct a series of annular-like hIAPP structures with different sizes and topologies. In the simulated lipid environments, the channels lose their initial continuous β-sheet network and break into oligomeric subunits, which are still loosely associated to form heterogeneous channel conformations. The channels' shapes, morphologies and dimensions are compatible with the doughnut-like images obtained by atomic force microscopy, and with those of modeled channels for Aβ, the β2-microglobulin-derived K3 peptides, and the β-hairpin-based channels of antimicrobial peptide PG-1. Further, all channels induce directional permeability of multiple ions across the bilayers from the lower to the upper leaflet. This similarity suggests that loosely-associated β-structure motifs can be a general feature of toxic, unregulated channels. In the absence of experimental high-resolution atomic structures of hIAPP channels in the membrane, this study represents a first attempt to delineate some of the main structural features of the hIAPP channels, for a better understanding of the origin of amyloid toxicity and the development of pharmaceutical agents.

All-d-Enantiomer of β-Amyloid Peptide Forms Ion Channels in Lipid Bilayers.

Alzheimer’s disease (AD) is the most common type of senile dementia in aging populations. Amyloid β (Aβ)-mediated dysregulation of ionic homeostasis is the prevailing underlying mechanism leading to synaptic degeneration and neuronal death. Aβ-dependent ionic dysregulation most likely occurs either directly via unregulated ionic transport through the membrane or indirectly via Aβ binding to cell membrane receptors and subsequent opening of existing ion channels or transporters. Receptor binding is expected to involve a high degree of stereospecificity. Here, we investigated whether an Aβ peptide enantiomer, whose entire sequence consists of d-amino acids, can form ion-conducting channels; these channels can directly mediate Aβ effects even in the absence of receptor–peptide interactions. Using complementary approaches of planar lipid bilayer (PLB) electrophysiological recordings and molecular dynamics (MD) simulations, we show that the d-Aβ isomer exhibits ion conductance behavior in the bilayer indistinguishable from that described earlier for the l-Aβ isomer. The d isomer forms channel-like pores with heterogeneous ionic conductance similar to the l-Aβ isomer channels, and the d-isomer channel conductance is blocked by Zn2+, a known blocker of l-Aβ isomer channels. MD simulations further verify formation of β-barrel-like Aβ channels with d- and l-isomers, illustrating that both d- and l-Aβ barrels can conduct cations. The calculated values of the single-channel conductance are approximately in the range of the experimental values. These findings are in agreement with amyloids forming Ca2+ leaking, unregulated channels in AD, and suggest that Aβ toxicity is mediated through a receptor-independent, nonstereoselective mechanism.

Support for removal of point-of-purchase tobacco advertising and displays: findings from the International Tobacco Control (ITC) Canada survey

BackgroundAlthough most countries now have at least some restrictions on tobacco marketing, the tobacco industry meet these restrictions by re-allocating expenditure to unregulated channels, such as at point-of-purchase.MethodsLongitudinal data from...

Maximum Phosphorylation of the Cardiac Ryanodine Receptor at Serine-2809 by Protein Kinase A Produces Unique Modifications to Channel Gating and Conductance Not Observed at Lower Levels of Phosphorylation

It is suggested that protein kinase A (PKA)-dependent phosphorylation of cardiac ryanodine receptors (RyR2) is linked to the development of heart failure and the generation of fatal cardiac arrhythmias. It is also suggested that RyR2 is phosphorylated to 75% of maximum levels in heart failure resulting in leaky, unregulated channels gating in subconductance states. We now demonstrate that this is unlikely, as RyR2 isolated from nonfailing cardiac muscle is phosphorylated to 75% of maximum at serine-2809, and in this situation, RyR2 displays low open probability (P(o)) (0.059+/-0.010 [SEM]; n=30) and normal regulation of gating by Ca(2+) and other ligands. However, when serine-2809 is PKA phosphorylated to maximum levels on RyR2, unique changes in channel behavior are observed. The channel displays enhanced single-channel conductance, very long open states causing large increases in P(o), and no evidence of subconductance states. Dephosphorylation of channels by protein phosphatase 1 (from 75% to near 0% at serine-2809) also enhances RyR2 channel activity through abbreviation of closed lifetimes. We propose that channels phosphorylated to 75% of maximum at serine-2809 occupy a natural low point in the RyR2 activity landscape. This optimizes channel control, which can be accomplished either by enhanced or decreased phosphorylation, making the channel particularly sensitive to the kinase:phosphatase balance. Pathological situations such as heart failure might upset this balance and thereby permit prolonged stoichiometric phosphorylation of serine-2809, which would be required for dysregulation of SR Ca(2+) release.

Human Trafficking in East Asia: Current Trends, Data Collection, and Knowledge Gaps

Migration in Asia is dynamic and complex especially intraregional movement of people. The volume of migration flows in the region has dramatically increased over the decades in terms of the overall number of migrants hosted by East Asian countries. The increase is alarming because some 30 to 40 per cent of total migration takes place through unregulated channels. It is unknown how much of this migration flow is human trafficking. However various studies and continuous media reports suggest that human trafficking is widespread throughout the region and on the rise. Trafficking in persons in East Asia has not been widely studied. This is rather curious because Japan for example has a large sex industry employing a significant number of non-Japanese women. As I will discuss later there are many challenges in conducting research on human trafficking in the region. As a result literature on the subject including research-based publications is rather limited particularly in comparison with the number of publications on trafficking in South-East and South Asia. Instead media reports and the United Nations (UN) and other agencies. intervention-oriented studies dominate the literature on East Asian trafficking. Such studies tend to focus on trafficking in women and children for sexual exploitation and highlight serious violations of human rights. Even though these studies are not empirically based and do not present survey results they still improve the understanding of the trafficking processes their underlying causes and impacts on the trafficked persons. (excerpt)

A Regulatory Domain in the C-terminal Extension of the Yeast Glycerol Channel Fps1p

The Saccharomyces cerevisiae gene FPS1 encodes an aquaglyceroporin of the major intrinsic protein (MIP) family. The main function of Fps1p seems to be the efflux of glycerol in the adaptation of the yeast cell to lower external osmolarity. Fps1p is an atypical member of the family, because the protein is much larger (669 amino acids) than most MIPs due to long hydrophilic extensions in both termini. We have shown previously that a short domain in the N-terminal extension of the protein is required for restricting glycerol transport through the channel (Tamás, M. J., Karlgren, S., Bill, R. M., Hedfalk, K., Allegri, L., Ferreira, M., Thevelein, J. M., Rydström, J., Mullins, J. G. L., and Hohmann, S. (2003) J. Biol. Chem. 278, 6337-6345). Deletion of the N-terminal domain results in an unregulated channel, loss of glycerol, and osmosensitivity. In this work we have investigated the role of the Fps1p C terminus (139 amino acids). A set of eight truncations has been constructed and tested in vivo in a yeast fps1Delta strain. We have performed growth tests, membrane localization following cell fractionation, and glycerol accumulation measurements as well as an investigation of the osmotic stress response. Our results show that the C-terminal extension is also involved in restricting transport through Fps1p. We have identified a sequence of 12 amino acids, residues 535-546, close to the sixth transmembrane domain. This element seems to be important for controlling Fps1p function. Similar to the N-terminal domain, the C-terminal domain is amphiphilic and has a potential to dip into the membrane.

Induction of an unregulated channel by mutations in adenine nucleotide translocase suggests an explanation for human ophthalmoplegia.

Adenine nucleotide translocase (Ant) is primarily involved in ATP/ADP exchange across the mitochondrial inner membrane. Recently, the A114P missense mutation in the human Ant1 protein was found to be associated with autosomal dominant progressive external ophthalmoplegia (adPEO). Ant1(A114P) was proposed to cause an imbalance of the mitochondrial deoxynucleotide pool that subsequently affects the accuracy of mtDNA replication, thereby leading to accumulation of mutant mtDNA. In the present study, it has been shown that the A128P mutation of the Saccharomyces cerevisiae Aac2 protein, equivalent to A114P in human Ant1p, does not always affect respiratory growth. However, expression of aac2(A128P) results in depolarization, structural swelling and disintegration of mitochondria, and ultimately an arrest of cell growth in a dominant-negative manner. The aac2(A128P) mutation likely induces an unregulated channel allowing free passage of solutes across the inner membrane. These data raise the possibility that the formation of an unregulated channel, rather than a defect in ATP/ADP exchange, is a direct pathogenic factor in human adPEO. The accumulation of mtDNA mutations might be a consequence of mitochondrial dysfunction.