Institutional Origins of Protective COVID-19 Public Health Policy Responses: Informational and Authority Redundancies and Policy Stringency

This is the author accepted manuscript. The final version is available from Now Publishers via the DOI in this recordIn this essay, we argue that institutional systems that allow redundancies in information channels and in policy-making are more likely to generate a rapid policy response to crises such as the onset of COVID-19 pandemic than more streamlined systems. Since democracies and decentralized polities feature higher informational and authority redundancies, we theorize improved crisis response in democracies, and in more decentralized democracies. To assess our theoretical expectations, we construct an original data set of stringency of policy measures that were adopted in response to COVID-19 by governments at different levels in 64~countries between January and May 2020. We find that democracies and liberal democracies responded to COVID-19 stronger and faster. Federalism and decentralization in addition to democratic institutions played a less uniform, but still a positive role. Beyond their other acknowledged merits, democratic institutions have superior capacity to mount a quick policy response to unqualified threats

COVID-19 Policy Response and the Rise of the Sub-National Governments

This is the author accepted manuscript. The final version is available from University of Toronto Press via the DOI in this recordData availability: The data used in this article are available as online Appendices C–G.We examine the roles of sub-national and national governments in Canada and the United States vis-à-vis the protective public health response in the onset phase of the global coronavirus disease 2019 (COVID-19) pandemic. This period was characterized in both countries by incomplete information as well as by uncertainty regarding which level of government should be responsible for which policies. The crisis represents an opportunity to study how national and sub-national governments respond to such policy challenges. In this article, we present a unique dataset that catalogues the policy responses of US states and Canadian provinces as well as those of the respective federal governments: the Protective Policy Index (PPI). We then compare the United States and Canada along several dimensions, including the absolute values of subnational levels of the index relative to the total protections enjoyed by citizens, the relationship between early threat (as measured by the mortality rate near the start of the public health crisis) and the evolution of the PPI, and finally the institutional and legislative origins of the protective health policies. We find that the sub-national contribution to policy is more important for both the United States and Canada than are their national-level policies, and it is unrelated in scope to our early threat measure. We also show that the institutional origin of the policies as evidenced by the COVID-19 response differs greatly between the two countries and has implications for the evolution of federalism in each

Federal Institutions and Strategic Policy Responses to COVID-19 Pandemic

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author.This essay examines the policy response of the federal and regional governments in federations to the COVID-19 crisis. We theorize that the COVID-19 policy response in federations is an outcome of strategic interaction among the federal and regional incumbents in the shadow of their varying accountability for health and the repercussions from the disruptive consequences of public health measures. Using the data from the COVID-19 Public Health Protective Policy Index Project, we study how the variables suggested by our theory correlate with the overall stringency of public health measures in federations as well as the contribution of the federal government to the making of these policies. Our results suggest that the public health measures taken in federations are at least as stringent as those in non-federations, and there is a cluster of federations on which a bulk of crisis policy making is carried by subnational governments. We find that the contribution of the federal government is, on average, higher in parliamentary systems; it appears to decline with the proximity of the next election in presidential republics, and to increase with the fragmentation of the legislative party system in parliamentary systems. Our analysis also suggests that when the federal government carries a significant share of responsibility for healthcare provision, it also tends to play a higher role in taking non-medical steps in response to the pandemic

The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins

The Ku-binding motif (KBM) is a short peptide module first identified in APLF that we now show is also present in Werner syndrome protein (WRN) and in Modulator of retrovirus infection homologue (MRI). We also identify a related but functionally distinct motif in XLF, WRN, MRI and PAXX, which we denote the XLF-like motif. We show that WRN possesses two KBMs; one at the N terminus next to the exonuclease domain and one at the C terminus next to an XLF-like motif. We reveal that the WRN C-terminal KBM and XLF-like motif function cooperatively to bind Ku complexes and that the N-terminal KBM mediates Ku-dependent stimulation of WRN exonuclease activity. We also show that WRN accelerates DSB repair by a mechanism requiring both KBMs, demonstrating the importance of WRN interaction with Ku. These data define a conserved family of KBMs that function as molecular tethers to recruit and/or stimulate enzymes during NHEJ

Protective Policy Index (PPI) global dataset of origins and stringency of COVID 19 mitigation policies

This the final version. Available on open access from Nature Research via the DOI in this recordData Records: We have created a Github repository (https://github.com/COVID-policy-response-lab/PPI-data) to store the datasets with the Public Health Protective Policy Index and its components. A copy of the included datafiles, as described below, was deposited with openICPSR15. It presently requires creating an account with the depository. Data access is free. Data location is at https://www.openicpsr.org/openicpsr/project/123401. The datasets are stored as csv files with five types of layouts. “PPI_country_m1.csv” is a file with country-level aggregates of region-level PPIs, computed using method 1, and their components. Each row corresponds to a country-date. The rows are identified using the country name (cname), numeric and 2-letter ISO 3166-1 codes (isocode and isoabbr respectively), as well as a date variable. The names of the policy variables contain four components: the name of the broader category, the name of the category, the level of issuing government (“nat” refers to the national policies, “reg” refers to the subnational policies, and “tot” refers to the combination of national and subnational policies), as well as suffix “ave”. For example, the average Total PPI is denoted as “ppi.all.tot.ave”, and the average stringency of the closures of air borders by the national government is denoted as “borders.air_bord.nat.ave”. See the codebook for the complete list of variables. “PPI_country_m2.csv” is a file with country-level aggregates of region-level PPIs, computed using method 2, and their components. The identifying variables and the naming convention for the policy variables is the same as in “PPI_country_m1.csv”, with the addition of suffix “0.2” at the end of the policy variable names. “PPI_regions_XX_m1.csv” (replace XX with the 2-letter ISO 3166-1 country codes) are country-specific files with region-specific PPIs, computed using method 1, and their components. The identifying variables include the numeric and 2-letter ISO 3166-1 codes of the country (isocode and isoabbr respectively), the name of the region (state_province), its ISO 3166-2 code (iso_state), as well as a date variable. The names of the policy variables contain three components: the name of the broader category, the name of the category, and the level of issuing government (“nat” refers to the national policies, “reg” refers to the subnational policies, and “tot” refers to the combination of national and subnational policies). For example, the average Total PPI is denoted as “ppi.all.tot”, and the stringency of the closures of air borders by the national government is denoted as “borders.air_bord.nat”. “PPI_regions_XX_m2.csv” (replace XX with the 2-letter ISO 3166-1 country codes are country-specific files with region-specific PPIs, computed using method 2, and their components. The identifying variables and the naming convention for the policy variables is the same as in “PPI_regions_XX_m1.csv”, with the addition of the suffix “0.2” at the end of the policy variable names. “changes_regions_m1.csv” is an auxiliary file that describes the changes in the policy states, as recorded in the “PPI_regions_XX_m1.csv” files. Each row in this file corresponds to a change in a value of a policy state variable in a region and of a specific government level. The case identifying variables include the name of the country (cname), the numeric and 2-letter ISO 3166-1 code of the country (isocode and isoabbr, respectively), the name of the region (state_province) and its ISO 3166-2 code, date, policy dimension, and a marker of policies issued by a regional government (subnational). Among others, the attributes included in this file include the branch of the government (branch) and the date when the change was announced (report_date).Code availability; The code used to produce our calculations is available at https://github.com/COVID-policy-response-lab/PPI-dataWe have developed and made accessible for multidisciplinary audience a unique global dataset of the behavior of political actors during the COVID-19 pandemic as measured by their policy-making efforts to protect their publics. The dataset presents consistently coded cross-national data at subnational and national levels on the daily level of stringency of public health policies by level of government overall and within specific policy categories, and reports branches of government that adopted these policies. The data on these public mandates of protective behaviors is collected from media announcements and government publications. The dataset allows comparisons of governments’ policy efforts and timing across the world and can serve as a source of information on policy determinants of pandemic outcomes–both societal and possibly medical

Laparoscopic fistula excision and omentoplasty for high rectovaginal fistulas: a prospective study of 40 patients

AIM: The aim of this study is to prospectively evaluate 40 patients with a high rectovaginal fistula treated by a laparoscopic fistula division and closure, followed by an omentoplasty. PATIENTS AND METHODS: Forty patients with a rectovaginal fistula, between the middle third of the rectum and the posterior vaginal fornix, resulting from different causes (IBD, iatrogenic and birth trauma) were treated by a laparoscopic excision of the fistula and insertion of an omentoplasty in the rectovaginal septum. The patients completed the gastrointestinal quality of life index questionnaire (GIQLI) and the Cleveland Clinic incontinence score (CCIS). All tests were performed at regular intervals after treatment. RESULTS: In 38 (95%) patients with a median age of 53 years (range 33-72), the surgical procedure was feasible. In two patients, the fistula was closed without an omentoplasty, and a diverting stoma was performed. The median follow-up was 28 months (range 10-35). Two patients (5%) developed a recurrent fistula. In one patient, the interposed omentum became necrotic and was successfully treated laparoscopically. In another patient, an abscess developed, which needed drainage procedures. The mean CCIS was 9 (range 7-10) before treatment and 10 (range 7-13) after treatment (p = 0.5 Wilcoxon). The median GIQLI score was 85 (range 34-129) before treatment and 120 (range75-142) after treatment (p = 0.0001, Wilcoxon). CONCLUSIONS: Laparoscopic fistula excision combined with omentoplasty is a good treatment modality with a high healing rate for high rectovaginal fistulas and an acceptable complication rate

Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome

Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified

Age-Related Neuronal Degeneration: Complementary Roles of Nucleotide Excision Repair and Transcription-Coupled Repair in Preventing Neuropathology

Neuronal degeneration is a hallmark of many DNA repair syndromes. Yet, how DNA damage causes neuronal degeneration and whether defects in different repair systems affect the brain differently is largely unknown. Here, we performed a systematic detailed analysis of neurodegenerative changes in mouse models deficient in nucleotide excision repair (NER) and transcription-coupled repair (TCR), two partially overlapping DNA repair systems that remove helix-distorting and transcription-blocking lesions, respectively, and that are associated with the UV-sensitive syndromes xeroderma pigmentosum (XP) and Cockayne syndrome (CS). TCR–deficient Csa−/− and Csb−/− CS mice showed activated microglia cells surrounding oligodendrocytes in regions with myelinated axons throughout the nervous system. This white matter microglia activation was not observed in NER–deficient Xpa−/− and Xpc−/− XP mice, but also occurred in XpdXPCS mice carrying a point mutation (G602D) in the Xpd gene that is associated with a combined XPCS disorder and causes a partial NER and TCR defect. The white matter abnormalities in TCR–deficient mice are compatible with focal dysmyelination in CS patients. Both TCR–deficient and NER–deficient mice showed no evidence for neuronal degeneration apart from p53 activation in sporadic (Csa−/−, Csb−/−) or highly sporadic (Xpa−/−, Xpc−/−) neurons and astrocytes. To examine to what extent overlap occurs between both repair systems, we generated TCR–deficient mice with selective inactivation of NER in postnatal neurons. These mice develop dramatic age-related cumulative neuronal loss indicating DNA damage substrate overlap and synergism between TCR and NER pathways in neurons, and they uncover the occurrence of spontaneous DNA injury that may trigger neuronal degeneration. We propose that, while Csa−/− and Csb−/− TCR–deficient mice represent powerful animal models to study the mechanisms underlying myelin abnormalities in CS, neuron-specific inactivation of NER in TCR–deficient mice represents a valuable model for the role of NER in neuronal maintenance and survival