Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis, i.e., megakaryopoiesis, thrombotic and thrombo-inflammatory actions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coronary syndrome (ACS) patients, and is also associated with improved functional recovery and prognosis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardiac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet-associated cardiovascular disorders, particularly in coronary artery disease (CAD) patients post-MI.

Enabling Nature-Based Solutions to Build Back Better—An Environmental Regulatory Impact Analysis of Green Infrastructure in Ontario, Canada

The application of green infrastructure in the built environment delivers a nature-based solution to address the impacts of climate change. This study presents a qualitative evidence synthesis that evaluates policy instruments which enable the use and implementation of green infrastructure, using Ontario, Canada as a case study. Unpacking the elements of the policy landscape that govern green infrastructure through environmental regulatory impact analysis can inform effective implementation of this nature-based solution and support decision-making in public policy. This environmental regulatory impact analysis is based on a systematic review of existing policy instruments, contextual framing in a continuum of coercion, and identification of alignment with relevant UN SDGs. Enabling widespread usage of green infrastructure in the built environment could be a viable strategy to build back better, localize the UN SDGs, and address multiple climate change impacts.

The Efficacy of Downward Counterfactual Thinking for Regulating Emotional Memories in Anxious Individuals

Aversive autobiographical memories sometimes prompt maladaptive emotional responses and contribute to affective dysfunction in anxiety and depression. One way to regulate the impact of such memories is to create a downward counterfactual thought–a mental simulation of how the event could have been worse–to put what occurred in a more positive light. Despite its intuitive appeal, counterfactual thinking has not been systematically studied for its regulatory efficacy. In the current study, we compared the regulatory impact of downward counterfactual thinking, temporal distancing, and memory rehearsal in 54 adult participants representing a spectrum of trait anxiety. Participants recalled regretful experiences and rated them on valence, arousal, regret, and episodic detail. Two to six days later, they created a downward counterfactual of the remembered event, thought of how they might feel about it 10 years from now, or simply rehearsed it. A day later, participants re-rated the phenomenological characteristics of the events. Across all participants, downward counterfactual thinking, temporal distancing, and memory rehearsal were equally effective at reducing negative affect associated with a memory. However, in individuals with higher trait anxiety, downward counterfactual thinking was more effective than rehearsal for reducing regret, and it was as effective as distancing in reducing arousal. We discuss these results in light of the functional theory of counterfactual thinking and suggest that they motivate further investigation into downward counterfactual thinking as a means to intentionally regulate emotional memories in affective disorders.

“Health in All Policies” Approach and Health Impact Assessment in Russia and the world

This study presents analysis of the international and Russian experience of implementation of “health in all policies” approach into legislation, as well as of health impact assessment. Certain steps towards the implementation of this approach have already been made in Russia, however, in general, there is still a lot to be done. It was revealed that the current system regulatory impact assessment (RIA) in Russia has a narrow focus and is focused on protecting the interests of business, which does not correspond to the well-established world practice, which presupposes complex RIA, including the impact of regulation on public health. Recommendations for strengthening the principle of “health by all policies” in Russian legislation and the introduction of the practice of assessing the regulatory impact on public health in Russia are presented.

POLITISASI BIROKRASI: Analisis Dampak Inkonsistensi Interpretasi Makna Pasal Dalam Undang-Undang Aparatur Sipil Negara

Politisasi birokrasi merupakan polemik yang menjadi benalu dalam penyelenggaraan pemerintahan yang hingga kini belum tuntas diatasi. Hal ini berdampak sangat buruk terhadap integritas ASN dan kualitas pelayanan publik yang diberikan kepada masyarakat. Sikap pejabat politik yang memanfaatkan birokrat demi kepentingan pribadi dan golongannya sangat menciderai profesionalisme para penyelenggara pemerintahan di bidang teknis tersebut. Permasalahan ini timbul karena biasnya makna ketentuan Pasal 1 Ayat (14) Undang-Undang Nomor 5 Tahun 2015 tentang Aparatur Sipil Negara bahwa Pejabat Pembina Kepegawaian (PPK) adalah pejabat yang mempunyai kewenangan menetapkan pengangkatan, pemindahan, dan pemberhentian pegawai ASN dan pembinaan manajemen ASN di instansi pemerintah. Untuk itu diperlukan. Untuk itu perlu dilakukan (1) Identifkasi permasalahan politisasi birokrasi dalam menetapkan pengangkatan, pemindahan, dan pemberhentian pegawai ASN oleh kepala daerah; dan (2) Analisa Alternatif kebijakan terbaik untuk mengatasi permasalahan tersebut. Penulis menggunakan metode deskriptif kualitatif karena mengkaji pola hubungan antara politik dan birokrasi dengan teori Interdependence between policy, poitic and administration dan Konsep dikotomi pejabat politik dan pejabat birokrasi kemudian melakukan analisa terhadap dampak regulasi ASN melalui metode Regulatory Impact Analysis (RIA) .

Smart legislative regulation: investigation of the behavior of the Czech RIA Committee

Motivation: This article studies the behavior of the Czech Regulatory Impact Assessment (RIA) Committee during the years between 2013–2018. This institution assesses RIAs of new laws and regulations which are in the process of ratification. Aim: The main aim was to find if the legislative change of February 3, 2016 had a direct impact on the decision-making of the Committee. Further, we ask whether there are other distinct patterns in the behavior of Czech RIA Committee members. Specifically, do the RIA Committee’s verdicts become more negative with time? We also investigate the level of independence of the Committee. In our analysis we used basic statistics: Chi-Square test of independence and regression analysis. To complete our study, we used data from a questionnaire which was distributed among RIA Committee members. Results: In our analysis we found that the legislative change did not have a direct immediate effect on the RIA Committee of the Czech Republic. However, we discovered that the RIA Committee has lost most of its independence and power in the six years of its existence. This change was gradual and most likely catalyzed by pressure from politicians. Further, voting per rollam yielded more positive results. We also discovered an institution whose RIA Committee verdicts differed significantly. Based on the findings of our research, we offer recommendations to the RIA Committee and other institutions with a similar purpose.

REGULATORY IMPACT ASSESSMENT IN THE AREA OF THE EURASIAN ECONOMIC UNION: PECULIARITIES OF FORMATION AND CURRENT STATUS

This article examines the process of formation of the regulatory impact assessment as a main tool of regulatory policy in the area of the Eurasian Economic Union. The influence of the taken regulatory measures on the activity of the entities is identified. The reasons for the necessity to develop regulatory impact assessment as a legal institution are described, its advantages are determined, the peculiarities of the development of this institution are studied. Legal framework that serves as a basis for assessment functioning is examined. The reasons for uneven development of the institution of assessment in the Eurasian area are understood, typical country peculiarities are given. On the basis of the conducted analysis suggestions for the improvement of the mechanism of the regulatory impact assessment are generated and its development perspectives are identified.

Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis i.e. megakaryopoiesis, thrombotic and thrombo-inflammatory ac-tions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coro-nary syndrome (ACS) patients, also associated with improved functional recovery and progno-sis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardi-ac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet associated cardiovascular dis-orders, particularly in coronary artery disease (CAD) patients post-MI.

IMPACTS OF INCREASING FREIGHT RAILWAY TARIFFS ON STATE ECONOMY

Based on global experience, the article proves the necessity of improving the analysis of regulatory impact of legislative acts, which is the main instrument of state regulation quality assurance. Recent years display the trend of temporal inland traffic freight railway tariffs increase. The last increase was approved by the corresponding Order of the Ministry of Infrastructure of Ukraine dd. August 11, 2021 qualified as a regulatory act, which is subject to compulsory regulatory impact analysis according to the Methodology approved at the national level. The national methodology does not provide for assessment of impacts on state economy. In view of this, the assessment was completed for the possible impact of regulatory act work on the state economy according to the methodological approach developed by the State Organization “Institute of the Economy and Forecasting of the National Academy of Sciences of Ukraine”, which main point is a more comprehensive and sophisticated quantitative assessment of the direct regulatory impact on the field of economic interest of both citizens, economic entities, state, and the society in general (national economy). The impact assessment of the freight railway tariffs’ increase on national economy followed two perspectives: the possible impact on GDP and the competition within the traffic infrastructure of Ukraine. The contribution of JSC “Ukrzaliznytsia” into GDP of Ukraine is computed based on freight railway tariffs increase. The article proves that the Order of the Ministry of Infrastructure of Ukraine will have the effects on intermodal competition within the transport system of Ukraine through the redistribution of the freight traffic as, on the one hand, certain off-grade freights will be handled by the river and motor transport and, on the other hand, specific 3rd rate class freights will be handled by the rail transport. Such redistribution will have positive effects for the competitive position of rail transport on the inner freight traffic market because the loss of some off-grade freights, which transport is unprofitable, will not have a negative impact on rail facilities.

Economics of Implementing Preemptive School Closures to Mitigate Pandemic Influenza Outbreaks of Differing Severity in the United States

The use of nonpharmaceutical interventions (NPIs) to slow disease spread, is a part of national pandemic preparedness as the first line of defense against influenza pandemics. Preemptive school closures (PSCs), an NPI reserved for use in severe pandemics, are highly effective in slowing influenza spread but have unintended consequences. We simulated PSC impacts during a 1957–like pandemic to estimate population impacts and quantify costs of closing schools at the national level. We also simulated 1957–like, 1968–like, and 2009–like pandemics at the Chicago regional level. We estimated economic impacts resulting from loss of income due to illness, providing childcare during closures, and other PSC costs while taking into consideration the number of cases averted with each mitigation strategy. The estimated net PSC costs ranged from $15 billion to $192 billion (2016 USD) (1957–like, national level) where between 2.3 and 47 million US cases may be averted depending on strategy. We found that 2–week school–by–school PSCs (as opposed to county–wide or school district–wide ones) had the lowest cost per discounted life–year gained for both national and Chicago regional–level analyses of all pandemics. While feasibility of such spatiotemporally precise triggering is presently questionable for most locales, this is, theoretically, an attractive option early in an outbreak, while assessing transmissibility and severity of a novel influenza virus. In contrast, we found that county–wide PSCs of longer durations (8 to 12 weeks) would result in the most averted cases (31–47 million) and deaths (105,000–156,000), albeit at considerably more cost ($125–$150 billion net of averted illness costs) for the national–level, 1957–like analysis. The estimated net costs per death averted ($1.0 to $1.2 million) for these scenarios compare favorably to the range of values recommended for regulatory impact analyses ($4.6 to 15.0 million). Hence, economic benefits of such PSCs would exceed the population impacts and economic costs.