Generic Agent Research Articles

Correlation between prescription volumes of generic antiepileptic drugs and the number of clinical epileptologists across prefectural regions in Japan: A descriptive study using a national claims database

PurposeAlthough generic drugs are essential in reducing medical costs, their use in epilepsy therapy remains a subject of ongoing debate. In this study, we analysed prescription trends of generic drugs using data from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. MethodsThe number of generic drug prescriptions from 2017–2021 was extracted from the NDB Open Data Japan, with data for each medication stratified by prefectural region, sex, and age, allowing for the analysis of the impact of each factor. We analysed the correlation between the prescription volumes of generic antiseizure medications (ASMs) and the number of clinical epileptologists registered with the Japan Epilepsy Society per 100,000 population. ResultsIn 2021, the prescription volume of generic ASMs was 49 %, whereas that for other pharmacological agents was between 70–80 %. Notably, for children < 15 years of age, generics made up approximately 20 % of prescriptions, which was significantly less than that in other age groups. Analysis by prefecture revealed a negative correlation between prescription volumes of ASMs and the number of clinical epileptologists across prefectural regions in Japan (R = −0.47, p < 0.01). ConclusionOur findings indicate that the higher the proportion of clinical epileptologists in each prefecture, the lower the number of prescribed generic ASMs. Clinical epileptologists in Japan therefore prescribe antiseizure agents in accordance with the Japanese epilepsy treatment guidelines that do not recommend the use of generic agents.

Combined Injection for Control of Iron-Deficiency Anemia and Coccidiosis in Piglets Decreases Stress at Management Time.

The aim of the present study was to assess the short-term behavioral and physiological responses of piglets to different treatment protocols for the control of iron-deficiency anemia (IDA) and cystoisosporosis. Piglets were treated with either (1) an injection of iron combined with an oral application of toltrazuril (TLZ) by drenching or (2) a combination injection of TZL + gleptoferron; the behavior of the piglets was then evaluated. For this study, 288 piglets were divided into three experimental groups: 96 piglets were kept untreated (control group); 96 piglets received an oral administration of a generic TZL-based anticoccidial agent (20 mg/kg BW) along with intramuscular administration of iron dextran (200 mg/mL; 1 mL/piglet) at the same handling (oral + parenteral group, O + P); and 96 piglets received an intramuscular application of the combination product (parenteral group, P). For each treated piglet, the total handling time, flight reaction, and the intensity and frequency of vocalizations were determined using the methodology described by Scollo et al. (2020). Piglets in the O + P group were found to emit more screams during treatment administration than animals in the P group (21.05% vs. 8.42% of animals; p < 0.05). Piglets in the O + P group reacted worse to manipulation and oral administration because a higher percentage of animals continued to fidget even after handling (32.63% vs. 12.63%; p < 0.05). Differences in growth performance between the groups were not observed in our study (p > 0.05). In conclusion, the administration of a combination product reduced stress during administration, as indicated by reduced vocalizations and reactions to manipulation.

Decoding the paradox: Understanding Elevated Hospitalization and Reduced Mortality in SARS-CoV-2 Variants

Introduction and aim: SARS-CoV-2 outbreaks occur cyclically, aligning with winter when vitamin D levels are lowest, except after new variant outbreaks. Adequate vitamin D is crucial for robust immune function. Hypovitaminosis diminishes immune responses, increasing susceptibility to viral infections. The manuscript explores the discrepancy between increased SARS-CoV-2 hospitalizations and lower mortality. Method​: SARS-CoV-2 mutants, including Delta, BQ, and XBB Omicron lineages, developed immune evasion capabilities, reducing the effectiveness of COVID-19 vaccines and bivalent boosters. The failure of COVID-19 vaccines to prevent infections and spread to others, coupled with the immune evasion exhibited by mutant viruses, contributed to continued SARS-CoV-2 outbreaks. Interestingly, dominant new mutants, despite their increased transmissibility, have caused fewer deaths. This article scrutinizes the mentioned incongruity through an analysis of published data. Results: Achieving herd immunity and eradicating SARS-CoV-2 has proven elusive due to ongoing mutagenesis and immune evasion, leading to recurrent viral outbreaks. The failure to approve repurposed early therapies for COVID-19 by regulators, as well as misinformation and weak strategies undertaken by leading health authorities, exacerbated the situation. Repurposed agents, including vitamin D and ivermectin, have demonstrated high efficacy against SARS-CoV-2 from the beginning, and remain unaffected by mutations. Despite their cost-effectiveness and widespread availability, regulatory approval for these generic agents in COVID-19 treatment is pending. Conclusion: Regulators hesitated to approve cost-effective, repurposed generic agents primarily to safeguard the temporary approval status of COVID-19 vaccines and anti-viral agents under Emergency Use Authorization, which persists. This reluctance overlooked the opportunity to implement an integrated approach with repurposed agents alongside COVID-19 vaccines, potentially reducing hospitalizations and fatalities and preventing outbreaks; this led to the failure to eradicate SARS-CoV-2 and becoming endemic. It is imperative that regulators now reconsider approving affordable generics for SARS-CoV-2 to effectively control future viral outbreaks. Non-technical Importance (Lay Abstract) Adequate vitamin D levels significantly bolster the human immune system—deficiency compromises immune responses and increases susceptibility, particularly to viruses. While new SARS-CoV-2 mutations like Omicron are less severe, they are more infectious and adept at evading immunity from vaccines; thus, they offer a limited spectrum of protection and duration. Primary COVID-19 vaccines have reduced disease severity but have failed to prevent viral spread, contributing to outbreaks. Booster doses had little effect on the virus but caused immune paresis, thus increasing susceptibility to infections. Regulators should consider approving generic, repurposed agents like vitamin D and ivermectin as adjunct therapies to address this challenge and better prepare for future pandemics. Proactively integrating vitamin D supplementation to fortify the immune system can mitigate vital outbreaks, alleviate hospital burdens, and reduce healthcare costs.

Dynamic system models and their simulation in the Semantic Web

Modelling and Simulation (M&amp;S) are core tools for designing, analysing and operating today’s industrial systems. They often also represent both a valuable asset and a significant investment. Typically, their use is constrained to a software environment intended to be used by engineers on a single computer. However, the knowledge relevant to a task involving modelling and simulation is in general distributed in nature, even across organizational boundaries, and may be large in volume. Therefore, it is desirable to increase the FAIRness (Findability, Accessibility, Interoperability, and Reuse) of M&amp;S capabilities; to enable their use in loosely coupled systems of systems; and to support their composition and execution by intelligent software agents. In this contribution, the suitability of Semantic Web technologies to achieve these goals is investigated and an open-source proof of concept-implementation based on the Functional Mock-up Interface (FMI) standard is presented. Specifically, models, model instances, and simulation results are exposed through a hypermedia API and an implementation of the Pragmatic Proof Algorithm (PPA) is used to successfully demonstrate the API’s use by a generic software agent. The solution shows an increased degree of FAIRness and fully supports its use in loosely coupled systems. The FAIRness could be further improved by providing more “ rich” (meta)data.

Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses.

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three-SARS, SARS-CoV-2 and MERS-are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.

Assessing Clinician Utilization of Next-Generation Antibiotics Against Resistant Gram-Negative Infections in U.S. Hospitals : A Retrospective Cohort Study.

The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards. To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics). Retrospective cohort. 619 U.S. hospitals. Adult inpatients. Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections. Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane-tazobactam (approved 2014) and ceftazidime-avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including "reserve" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage. Residual confounding. Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety-efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization. U.S. Food and Drug Administration; NIH Intramural Research Program.

Impact of varied immunosuppressive agents and post-transplant diabetes mellitus on prognosis among diverse transplant recipients (experimental studies).

The success of solid organ transplantation (SOT) and the use of immunosuppressive agents offer hope to patients with end-stage diseases. However, the impact of post-transplant diabetes mellitus (PTDM) on SOT patients has become increasingly evident. In our study, we utilized the Scientific Registry of Transplant Recipients (SRTR) database to investigate the association between PTDM and patient survival in various types of organ transplantations, including liver, kidney, intestinal, heart, lung, and combined heart-lung transplantations (all P <0.001). Our findings revealed a negative effect of PTDM on the survival of these patients. Furthermore, we examined the effects of both generic and innovator immunosuppressive agents on the development of PTDM and the overall survival of different SOT populations. Interestingly, the results were inconsistent, indicating that the impact of these agents may vary depending on the specific type of transplantation and patient population. Overall, our study provides a comprehensive and systematic assessment of the effects of different immunosuppressive agents on prognosis, as well as the impact of PTDM on the survival of patients undergoing various types of SOT. These findings emphasize the need for further research and highlight the importance of optimizing immunosuppressive regimens and managing PTDM in SOT patients to improve their long-term outcomes.

The Impact of Withholding Cost-Effective Early Treatments, such as Vitamin D, on COVID-19: An Analysis Using an Innovative Logical ParadigmThe Impact of Withholding Cost-Effective Early Treatments, such as Vitamin D, on COVID-19: An Analysis Using an Inno

Purpose: While numerous widely accepted nutraceuticals lack randomized clinical trial (RCT) validation, regulatory bodies prioritize RCTs as the primary evidence for testing hypotheses for drug approvals. Despite challenges in authorizing generic therapies for SARS-CoV-2, regulatory bodies promptly granted Emergency Use Authorization for patented agents. This study evaluated whether the clinical trial data yielded adequate evidence to justify the approval of generic compounds, like vitamin D, as adjunct therapy to combat SARS-CoV-2. Methods: We employed an ancient logic system, seamlessly integrated with modern scientific principles and artificial intelligence principles, to analyze empirical data from 7 papers published in 2020. Subsequently, we compared the results with over 200 scientific papers (including over 100 treatment studies) referenced in a large (big)database. This study aimed to determine if there was substantial evidence in 2020 to support the approval of generic agents such as vitamin D (and ivermectin) for treating COVID-19. Results: The drug approval process undervalues well-designed observational studies, placing them in a subordinate position to RCTs when assessing effectiveness, even for nutrients. Our utilization of Catuskoti, an innovative logical method, highlights its potential as a catalyst for scientific progress, including big data analysis and integrating artificial intelligence into nutrient and pharmaceutical approval processes. Conclusions: Analyses conducted within this logical framework affirmed a robust inverse correlation between vitamin D levels and positive clinical outcomes in COVID-19 cases. Emphasizing the broader adoption of Catuskoti logic, particularly in analyzing big data and Machine Learning paradigms, becomes crucial in drug approvals. This approach aims to mitigate harm to individuals in future pandemics by promptly providing a more comprehensive understanding of the relationships between variables.

Embodied cognitive morphogenesis as a route to intelligent systems.

The embryological view of development is that coordinated gene expression, cellular physics and migration provides the basis for phenotypic complexity. This stands in contrast with the prevailing view of embodied cognition, which claims that informational feedback between organisms and their environment is key to the emergence of intelligent behaviours. We aim to unite these two perspectives as embodied cognitive morphogenesis, in which morphogenetic symmetry breaking produces specialized organismal subsystems which serve as a substrate for the emergence of autonomous behaviours. As embodied cognitive morphogenesis produces fluctuating phenotypic asymmetry and the emergence of information processing subsystems, we observe three distinct properties: acquisition, generativity and transformation. Using a generic organismal agent, such properties are captured through models such as tensegrity networks, differentiation trees and embodied hypernetworks, providing a means to identify the context of various symmetry-breaking events in developmental time. Related concepts that help us define this phenotype further include concepts such as modularity, homeostasis and 4E (embodied, enactive, embedded and extended) cognition. We conclude by considering these autonomous developmental systems as a process called connectogenesis, connecting various parts of the emerged phenotype into an approach useful for the analysis of organisms and the design of bioinspired computational agents.

The Will to Nothingness: An Essay on Nietzsche’s On the Genealogy of Morality

<i>The Will to Nothingness: An Essay on Nietzsche’s On the Genealogy of Morality</i>

Neuropharmacology of Alcohol Addiction with Special Emphasis on Proteomic Approaches for Identification of Novel Therapeutic Targets.

Alcohol is a generic pharmacological agent with only a few recognized primary targets. Nmethyl- D-aspartate, gamma-aminobutyric acid, glycine, 5-hydroxytryptamine 3 (serotonin), nicotinic acetylcholine receptors, and L-type Ca2+ channels and G-protein-activated inwardly rectifying K channels are all involved. Following the first hit of alcohol on specific brain targets, the second wave of indirect effects on various neurotransmitter/neuropeptide systems begins, leading to the typical acute behavioral effects of alcohol, which range from disinhibition to sedation and even hypnosis as alcohol concentrations rise. Recent research has revealed that gene regulation is significantly more complex than previously thought and does not fully explain changes in protein levels. As a result, studying the proteome directly, which differs from the genome/transcriptome in terms of complexity and dynamicity, has provided unique insights into extraordinary advances in proteomic techniques that have changed the way we can analyze the composition, regulation, and function of protein complexes and pathways underlying altered neurobiological conditions. Neuroproteomics has the potential to revolutionize alcohol research by allowing researchers to gain a better knowledge of how alcohol impacts protein structure, function, connections, and networks on a global scale. The amount of information collected from these breakthroughs can aid in identifying valuable biomarkers for early detection and improved prognosis of an alcohol use disorder and future pharmaceutical targets for the treatment of alcoholism.

A Generic Intelligent Agent Design Approach Based on Artificial Neural Networks

A Generic Intelligent Agent Design Approach Based on Artificial Neural Networks

Critical Nash Value Nodes for Control Affine Embedded Graphon Mean Field Games*

Graphon Mean Field Games (GMFGs) (Caines and Huang (2021)) constitute generalizations of Mean Field Games to the case where the agents form subpopulations associated with the nodes of large graphs. The work in (Foguen-Tchuendom et al. (2021), Foguen-Tchuendom et al. (2022a)) analyzed the stationarity of equilibrium Nash values with respect to node location for large populations of non-cooperative agents with linear dynamics on large graphs embedded in Euclidean space together with their limits (termed embedded graphons). That analysis is extended in this investigation to agent systems lying in the class of control affine non-linear systems (see Isidori (1985)). Specifically, control affine GMFG systems are treated where (i) at each node αeV the drift of each generic agent system is affine in the control function, and (ii) the running costs at each node α ϵ V ⊂ Rm are exponentiated negative inverse quadratic (ENIQ) functions of the difference between a generic state and the local graphon weighted mean Zα,µG where µG:= {µβ,β ϵ V ⊂ Rm} is the globally distributed family of mean fields. The infinite cardinality node and edge limits are considered, where it is assumed that the limit embedded graphon g(α, β), (α, β) ϵ V x V, is continuously differentiable. It is shown that the equilibrium Nash value Vα is stationary with respect to the nodal location α ϵ V if and only if the corresponding mean Zα,µG is stationary with respect to nodal location.

Abstract IA006: Reverse-engineering discovery of targets, involved cell types, and compounds for liver cancer chemoprevention

Abstract Hepatocellular carcinoma (HCC) is a cancer type with clinically unequivocal and well-defined predisposing conditions, namely chronic fibrotic liver diseases caused by viral hepatitis and metabolic disorders. By following up the at-risk patient cohort, natural history of HCC development can be captured over the timeframe of one to two decades. Archived biospecimens are often available from the time of initial liver disease diagnosis, and unbiased molecular profiling of the specimens provides unique opportunities to interrogate molecular dysregulations confidently correlated with the real long-term clinical outcome, i.e., HCC development from early-stage liver diseases. This “reverse-engineering” strategy helps increase the likelihood of identifying clinically relevant therapeutic targets without solely relying on data from experimental preclinical models. This is particularly useful in cancer chemoprevention target discovery given the the requirement of overwhelmingly lengthy and costly clinical validation of experimentally derived candidate targets, which is often practically infeasible. Utilizing this strategy, we could successfully identify HCC chemoprevention targets (e.g., cellular signaling such as EGFR pathway, circulating bioactive lipids), involved cell types (e.g., hepatic myofibroblasts, conventional dendritic cells), and compounds (e.g., small molecular signaling pathway inhibitors, generic agents), streamline the process of their clinical validation, and facilitate translation of promising chemoprevention agents to the care of liver disease patients. Citation Format: Yujin Hoshida. Reverse-engineering discovery of targets, involved cell types, and compounds for liver cancer chemoprevention [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA006.

러시아어 중간문의 의미와 범위에 관한 연구 : 조력적 중간문을 중심으로

Middle voice is a construction that is difficult to define from the viewpoint of the voice as a dual system with passive and active constructions. Middle constructions are classified into several detailed semantic types. Among them, facilitative middles are the subject of this study. Facilitative middles in Russian mainly present the degree to which the object of the underlying transitive verb (promoted to the position of syntactic subject) is likely to be put into action. Therefore, the facilitative middles consist of a subject (the object of the underlying transitive verb), a present tense form of a reflexive verb derived from an imperfective transitive verb, and generic agent that is not explicitly expressed. In addition, many middle constructions combine with adverbial phrases of manner that indicate how an action is carried out.BR This study examines the semantic and structural properties of facilitative middles in Russian, focusing on subject, verb, agent, and adverbial phrases, and analyzes the attributes of Russian facilitative middles through comparison with related constructions. The findings and conclusions are as follows.BR First, the typical attributive meaning of facilitative middles is derived from the specific tense aspect form of the verb, namely the present imperfective verb form. Thus, when the verb tense is changed to the past, the possibility and potential of the action is weakened and when the aspect of the verb is changed to the perfective, the genericity and conventionality of the action disappear, consequently shifting to the interpretation of anticausative constructions.BR Second, while generic agents cannot be specified and are only implied, non-generic agents can be specified through the “у” prepositional phrase. However, in this case, the cause of and responsibility for the action performed can be ascribed to the agent expressed through the prepositional phrase, not the subject; hence, the sentence obtains an interpretation similar to the passive.BR Third, facilitative middles have modal meanings of potential and possibility in the sense that the object is likely to be subjected to an action. In particular, facilitative middles combine with various adverbial phrases with manner meanings.BR Finally, there are the similar constructions that promote arguments other than the object of the underlying transitive verb as the subject. These are instrument-subject constructions and antipassive. These constructions are formed from a much narrower range of verbs than middle constructions. Therefore, the Russian middles are closely related to the passive, anticausative, antipassive, instrument-subject constructions and generalized personal constructions in accordance with the tense aspect form of verb, the genericity of the agent and the semantic role of the subject, among others.

A review of clinical efficacy data supporting emergency use authorization for COVID-19 therapeutics and lessons for future pandemics.

Emergency Use Authorization (EUA) allows the US Food and Drug Administration (FDA) to expedite the availability of therapeutics in the context of a public health emergency. To date, an evidentiary standard for clinical efficacy to support an EUA has not yet been established. This review examines the clinical data submitted in support of EUA for antiviral and anti‐inflammatory therapeutics for coronavirus disease 2019 (COVID‐19) through December of 2021 and the resilience of the authorization as new clinical data arose subsequent to the authorization. In the vast majority of cases, EUA was supported by at least one well‐powered randomized controlled trial (RCT) where statistically significant efficacy was demonstrated. This included branded medications already approved for use outside of the context of COVID‐19. When used, the standard of a single RCT seemed to provide adequate evidence of clinical efficacy, such that subsequent clinical studies generally supported or expanded the EUA of the therapeutic in question. The lone generic agent that was granted EUA (chloroquine/hydroxychloroquine) was not supported by a well‐controlled RCT, and the EUA was withdrawn within 3 months time. This highlighted not only the ambiguity of the EUA standard, but also the need to provide avenues through which high quality clinical evidence for the efficacy of a generic medication could be obtained. Therefore, maintaining the clinical trial networks assembled during the COVID‐19 pandemic could be a critical component of our preparation for future pandemics. Consideration could also be given to establishing a single successful RCT as regulatory guidance for obtaining an EUA.

Out of New Guinea? Two new species of Zygogynum (Winteraceae) extend the genus west of Lydekker’s and Wallace’s Lines

SummaryThe Winteraceae comprise 100 – 130 species in five to nine genera. The genus Zygogynum is currently thought to have a Papuasian-Pacific distribution and is only known from the western Pacific islands (New Caledonia, Vanuatu and the Solomon Islands), Australia and New Guinea, including the far western Bird’s Head Peninsula, but is not yet recorded from islands to the west of the Sahul Plate and the biogeographic boundary of Lydekker’s Line. Here, two new species of Zygogynum are described from west of both Wallace’s and Lydekker’s Lines. Zygogynum moluccanum is described from the Moluccan islands of Indonesia, and Z. sundaicum, a new species and generic record for the Sunda shelf, is described from the northern part of the Malaysian State of Sarawak in Borneo. In addition to descriptions and illustrations of the new species, the generic delimitation, fossil record and potential dispersal agents of Zygogynum are discussed.

Secure Bipartite Tracking Control for Linear Leader-Following Multiagent Systems Under Denial-of-Service Attacks

Dear editor, This letter puts forward a secure feedback control scheme to bipartite tracking consensus for a set of generic linear autonomous agents subject to aperiodic and unknown denial-of-service (DoS) attacks. In contrast to the DoS attack model that disables all transmission channels simultaneously, we are concerned with a general DoS attack model with independent attacks over each transmission channel. Such malicious attacks not only destroy the connectivity of underlying network, but also induce the dynamic transmission of reachable information. A time-varying error system is built upon the proposed distributed controller and the designed feedback matrix. A sufficient condition in terms of the frequency and duration of DoS attacks is developed with the assistance of some techniques from graph theory and non-negative matrix theory such that the state error is guaranteed to asymptotically approach zero. In particular, our results are proved to be applicable for a class of multiagent systems (MASs) with the strictly unstable system matrix.

Cancer Medicines: What Is Essential and Affordable in India?

The WHO essential medicines list (EML) guides selection of drugs for national formularies. Here, we evaluate which medicines are considered highest priority by Indian oncologists and the extent to which they are available in routine practice. This is a secondary analysis of an electronic survey developed by the WHO EML Cancer Medicine Working Group. The survey was distributed globally using a hierarchical snowball method to physicians who prescribe systemic anticancer therapy. The survey captured the 10 medicines oncologists considered highest priority for population health and their availability in routine practice. The global study cohort included 948 respondents from 82 countries; 98 were from India and 67 were from other low- and middle-income countries. Compared with other low- and middle-income countries, the Indian cohort was more likely to be medical oncologist (70% v 31%, P < .001) and work exclusively in the private health system (52% v 17%, P < .001). 14/20 most commonly selected medicines were conventional cytotoxic drugs. Universal access to these medicines was reported by a minority of oncologists; risks of significant out-of-pocket expenditures for each medicine were reported by 19%-58% of oncologists. Risk of catastrophic expenditure was reported by 58%-67% of oncologists for rituximab and trastuzumab. Risks of financial toxicity were substantially higher within the private health system compared with the public system. Most high-priority cancer medicines identified by Indian oncologists are generic chemotherapy agents that provide substantial improvements in survival and are already included in WHO EML. Access to these treatments remains limited by major financial burdens experienced by patients. This is particularly acute within the private health system. Strategies are urgently needed to ensure that high-quality cancer care is affordable and accessible to all patients in India.

Open data and model integration through generic model agent toolkit in CyberWater framework

The CyberWater project is created to develop an open data and open model integration framework for studying complex environmental and water problems, where diverse online data sources can be directly accessed by diverse models without any need of users’ extra effort on the tedious tasks of data preparation for their models. We present our design and development of a novel generic model agent toolkit in the context of CyberWater, which enables users to integrate their models into the CyberWater system without writing any new code, significantly simplifying the data and model integration task. CyberWater adopts a visual scientific workflow system, VisTrails, which also supports provenance and reproducible computing. Our approach and the developed generic model agent toolkit are demonstrated, via CyberWater framework, with automated and flexible workflows through integrating data and models using real-world use cases. Two popular hydrological models, VIC and DHSVM, are used for illustrations.