Candidate genes of the development of antipsychotic-induced parkinsonism in patients with schizophrenia

Antipsychotic-induced parkinsonism is an undesirable reaction from the extrapyramidal system that occurs against the background of taking antipsychotics (AP), more often in patients with schizophrenia. Antipsychotic-induced parkinsonism belongs to the group of secondary parkinsonism. Its prevalence in the world is about 36%. It is assumed that this undesirable AP reaction is genetically determined. In recent years, numerous associative genetic studies of predisposition to the development of antipsychotic-induced parkinsonism have been conducted. However, the research results are contradictory.Purpose. Review of the results of studies of genetic predictors of antipsychotic-induced parkinsonism in patients with schizophrenia.Materials and methods. We searched for full-text publications in Russian and English in the RSCI, PubMed, Web of Science, Springer databases using keywords and combined searches for words over the past decade.Results. The review considers candidate genes encoding proteins/enzymes involved in the pharmacodynamics and pharmacokinetics of AP. We analyzed 23 genome-wide studies examining 108 genetic variations, including SNV/polymorphisms of 26 candidate genes involved in the development of AIP in schizophrenic patients. Among such a set of obtained results, only 22 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3; VNTR*9R DAT1; rs4680 (G/A) СOMT; rs6311 (C/T) 5HTR2A; rs6318 (C/G), rs3813929 (С/Т), haplotype-997G, -759C, -697C и 68G HTR2C; rs2179652 (C/T), rs2746073 (T/A), rs4606 (C/G), rs1152746 (A/G), rs1819741 (С/Т), rs1933695 (G/A), haplotype rs1933695-G, rs2179652-C, rs4606-C, rs1819741-T и rs1152746-G, haplotype rs1933695-G, rs2179652-T, rs4606-G, rs1819741-C и rs1152746-A RGS2; haplotype TCCTC ADORA2A; rs4795390 (C/G) PPP1R1B; rs6265 (G/A) BDNF; rs12678719 (C/G) ZFPM2; rs938112 (C/A) LSMAP; rs2987902 (A/T) ABL1; HLA-B44; rs16947 (A/G), rs1135824 (A/G), rs3892097 (A/G), rs28371733 (A/G), rs5030867 (A/C), rs5030865 (A/C), rs1065852 (C/T), rs5030863 (C/G), rs5030862 (A/G), rs28371706 (C/T), rs28371725 (A/G), rs1080983 (A/G) CYP2D6. However, at the present time it should be recognized that there is no final or unique decision about the leading role of any particular SNV/polymorphism in the development of AIP.Conclusion. Disclosure of genetic predictors of AP-induced parkinsonism development may provide a key to the development of a strategy for personalized prevention and treatment of the neurological complication of AP-therapy of schizophrenia in real clinical practice.

Next-Generation EEW Empowered by NDSHA: From Concept to Implementation

In this paper, we discuss a possible combination of Earthquake Early Warning (EEW) and Neo-deterministic Seismic Hazard Assessment (NDSHA), and propose a new warning model, EEW2.0. The aim is to provide a differentiated warning alert to various end-users based on the results of seismic hazard assessment evaluation. The implementation of such a system contains three basic steps: (a) classification of “potential to cause hazard” in terms of magnitude; (b) determination of the source areas and building a hazard database in terms of Modified Mercalli Intensity (MMI) maps, considering all possible earthquake scenarios in the source area, for the whole protected area; (3) equipping unique decision framework for specific end-users. When a damaging earthquake (M ≥ 5.0) is detected, EEW2.0 quickly matches the prepared MMI map by estimated magnitude and epicenter, then directly extracts the MMI value and issues an early warning to the public. With the great attention and resources put into the reduction in seismic and its secondary risk in the 21st century, the proposed EEW2.0 will likely play an active role in protecting lives and reducing economic losses.

Candidate Genes Encoding Dopamine Receptors as Predictors of the Risk of Antipsychotic-Induced Parkinsonism and Tardive Dyskinesia in Schizophrenic Patients

(1) Introduction: Extrapyramidal disorders form the so-called extrapyramidal syndrome (EPS), which is characterized by the occurrence of motor disorders as a result of damage to the basal ganglia and the subcortical-thalamic connections. Often, this syndrome develops while taking medications, in particular antipsychotics (APs). (2) Purpose: To review studies of candidate genes encoding dopamine receptors as genetic predictors of development of AP-induced parkinsonism (AIP) and AP-induced tardive dyskinesia (AITD) in patients with schizophrenia. (3) Materials and Methods: A search was carried out for publications of PubMed, Web of Science, Springer, and e-Library databases by keywords and their combinations over the last 10 years. In addition, the review includes earlier publications of historical interest. Despite extensive searches of these commonly used databases and search terms, it cannot be ruled out that some publications were possibly missed. (4) Results: The review considers candidate genes encoding dopamine receptors involved in pharmacodynamics, including genes DRD1, DRD2, DRD3, and DRD4. We analyzed 18 genome-wide studies examining 37 genetic variations, including single nucleotide variants (SNVs)/polymorphisms of four candidate genes involved in the development of AIP and AITD in patients with schizophrenia. Among such a set of obtained results, only 14 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3 with AIP and rs4532 (A/G) DRD1, rs6277 (C/T), rs6275 (C/T), rs1800497 (C/T), rs1079597 (A/G), rs1799732 (141CIns/Del), rs1045280 (C/G) DRD2, rs6280 (C/T), rs905568 (C/G) DRD3 with AITD. However, at present, it should be recognized that there is no final or unique decision on the leading role of any particular SNVs/polymorphisms in the development of AIP and AITD. (5) Conclusion: Disclosure of genetic predictors of the development of AIP and AITD, as the most common neurological adverse drug reactions (ADRs) in the treatment of patients with psychiatric disorders, may provide a key to the development of a strategy for personalized prevention and treatment of the considered complication of AP therapy for schizophrenia in real clinical practice.

VIII. Parakatatheke und letztwillige Verfügungen: Zum Hintergrund von D. 32,37,5

Parakatatheke and last wills: on the background of D. 32.37.5. Already Hans Julius Wolff refused the idea of a hermetical isolation between Roman law and local (provincial) legal practice in everyday life. Following his trace, this contribution will show that legal intercourse between different classes of provincial populace was far more intensive than generally assumed. Focusing on the period before the Constitutio Antoniniana (212 AD), a detailed exegesis of a unique decision of Scaevola follows. The Roman jurist delivers a paradigmatic case: He settles a dispute in which the Greek formula of parakatatheke was used by a Roman citizen for disposing about his assets on death. In fact, the legal act should be considered ineffective under Roman law. However, Scaevola looked for ways to enforce the claim. Roman law and provincial legal custom: Scaevola’s decision sheds a new light on the creative approach of Roman jurisdiction regarding foreign legal thoughts.

Considering Roadway Context in Setting Posted Speed Limits

The National Cooperative Highway Research Program (NCHRP) Project 17-76 investigated factors that influence operating speed and safety through a review of the literature and an analysis of the relationships for speed, safety, and roadway characteristics on urban/suburban streets. That knowledge, along with a review of existing speed limit setting practices, was used to develop a Speed Limit Setting Procedure (SLS-Procedure) as well as a user manual to explain the SLS-Procedure. In addition, the SLS-Procedure was automated via a spreadsheet-based Speed Limit Setting Tool (SLS-Tool). These products will permit engineers to make informed decisions about the setting of speed limits. The SLS-Procedure is fact based and transparent, relying on a set of decision rules that consider both driver speed choice and safety associated with the roadway. The SLS-Procedure was designed to be applicable across different roadway types and contexts by having a set of unique decision rules for four combinations of roadway types and contexts: limited-access, undeveloped, developed, and full-access facilities. The SLS-Procedure uses the operating speed distribution as a starting point for the suggested speed limit, with the resulting suggested value based on consideration of roadway type, context, safety performance, and other characteristics.

Agent-Based Modeling of Decisions and Developer Actions in Wind Farm Landowner Contract Acceptance

This paper presents an agent-based model to investigate interactions between wind farm developers and landowners. Wind farms require hundreds of square miles of land for development and developers typically interact with landowners to lease land for construction and operations. Landowners sign land lease contracts without knowing the turbine layout, which affects aesthetics of property as well as value of the lease contract. Having a turbine placed on one's land is much more lucrative than alternative land uses, but landowners must sign over the use of their land without knowing whether they will receive this financial benefit or not. This process, typically referred to as “Landowner Acquisition,” is highly uncertain for both stakeholders—a source stated up to 50% of wind projects fail due to landowner acquisition issues. We present an agent-based model to study the landowner acquisition period with unique decision-making characteristics for nine landowners and a developer. Citizen participation is crucial to the acceptance of wind farms; thus, we use past studies to quantify three actions a developer can take to influence landowners: (1) community engagement meetings, (2) preliminary environmental studies, and (3) sharing the wind turbine layout with the landowner. Results show how landowner acceptance rates can change over time based on what actions the developer takes. While still in the “proof of concept” stage, this model provides a framework for quantifying wind stakeholder interactions and potential developer actions. Suggestions for how to validate the framework in the future are included in the discussion.

Using Applied Decision Analysis to Understand Foreign Policy Decision-Making

A leader’s approach to foreign policy decision-making is a critical explanatory factor in understanding why certain decisions are made. While several tools are available to analysts who wish to examine the process by which decision makers settle upon their chosen alternative, one of the most compelling is applied decision analysis (ADA), which allows scholars to uncover the unique “decision DNA” associated with a given leader. This chapter surveys the literature that has used the ADA methodology to examine questions of foreign policy decision-making. It pulls from twenty studies of leaders’ decisions—with more than twenty different leaders, ranging from Winston Churchill to Mao Zedong to Osama bin Laden—which comprise more than one hundred total unique decisions, examining and discussing the findings of each. It draws inferences about which decision rules best explain leaders’ policy choices, concluding that the works in question show overwhelming support for the poliheuristic theory of decision; and it discusses how future scholars can build on the ADA research program and how this information can best be used by policymakers.

Agent-Based Modeling of Decisions and Developer Actions in Wind Farm Landowner Contract Acceptance

This paper presents an agent-based model to investigate interactions between wind farm developers and landowners. Wind farms require hundreds of square miles of land for development and developers typically interact with landowners to lease land for construction and operations. Landowners sign land lease contracts without knowing the turbine layout, which affects aesthetics of property as well as value of the lease contract. Having a turbine placed on one’s land is much more lucrative than not, but landowners have to sign over the use of their land without knowing if they will receive this financial benefit or not. The timing of this process, typically referred to as “Landowner Acquisition,” introduces high uncertainty for both stakeholders and represents a major pain point of the industry — a source stated up to 50% of wind projects fail due to landowner acquisition issues. We present an agent-based model that models the land lease contract period with unique decision-making characteristics for a set of landowners and a wind farm developer. Citizen participation is an integral part of community acceptance of wind farms, thus we use principles from past studies to quantify three actions a developer can take to influence landowner decisions: (1) community engagement meetings; (2) preliminary environmental studies; and (3) sharing the wind turbine layout with the landowner. The results show how landowner acceptance rates can potentially change over time based on what actions the developer takes. Overall, developers can use this model to better understand interactions with landowners and determine what actions may help positively influence landowner acceptance rates.

Exposures and Conditions of Acute Environmental Origin

Investigations of acute events with suspected environmental associations include unique decision points and action steps. Public health professionals should prepare to respond to these investigations by maintaining expertise in fields including toxicology, environmental epidemiology, environmental and occupational medicine, industrial hygiene, environmental risk assessment, and environmental monitoring. Notification of a disease cluster or of an acute exposure event is often the initial trigger for public health awareness of the situation. Setting case definitions and characterizing exposure can be challenging, and input might be needed from subject matter experts, responders, and partners outside of public health. Quantifying the magnitude and route of exposure, understanding the inherent toxicity and duration of exposure, and other factors are unique steps in environmental investigations. Effective risk communication to affected communities and involved partners is critical and should be carefully planned.