Worldwide Database Research Articles

Targeted Screening of the C9orf72 Gene in Bulgarian Amyotrophic Lateral Sclerosis Patients

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized by progressive degeneration of the upper and lower motor neurons, leading to muscle weakness, hypotrophy, swallowing and respiratory failure. The cause of ALS is not yet fully elucidated, but there are 35 associated genes and 2 gene loci with an unidentified gene. The most common are C9orf72, SOD1, TARDBP and FUS found in approximately 10% of patients. Variants in the C9orf72 gene are the main cause of fALS – 25-40% of cases (and a small percentage of sALS). The goal of the present study was to evaluate the significance of the C9orf72 hexanucleotide repeat expansion in Bulgarian patients with ALS, through the means of in house and triplet repeat-primed PCR assay (TP-PCR). From 171 patients diagnosed with ALS and included in the current study, we have identified the repeat expansion with more than 145 GGGGCC repeats in 7 (4,1%). Short expansions or borderline values (24 to 30 repeats) were not detected. Due to absence of sufficient data, we have established an ALS-focused research for the association of the C9orf72 gene in clinically well-characterized Bulgarian ALS patients. Published data show variable percentage ratios for genetically verified cases (4-40%), which is mainly due to small sample counts and sALS-fALS ratios. Our patients’ group also contains sALS and fALS cases, which explains the low percentage of genetic verification. The obtained results enrich the worldwide database and shed light onto genetically characterized Bulgarian ALS patients. Affected patients and their families can receive adequate medical-genetic consultation and prenatal diagnostic testing.

Molecular and in silico typing of the lipooligosaccharide biosynthesis gene cluster in Campylobacter jejuni and Campylobacter coli.

The extensive genetic variation in the lipooligosaccharide (LOS) core biosynthesis gene cluster has led to the development of a classification system; with 8 classes (I-VIII) for Campylobacter coli (C. coli) LOS region and with 23 classes (A-W) or four groups (1–4) for Campylobacter jejuni (C. jejuni) LOS region. PCR based LOS locus type identification for C. jejuni clinical isolates from a UK hospital as well as in silico LOS locus analysis for C. jejuni and C. coli genome sequences from GenBank was carried out to determine the frequencies of various LOS genotypes in C. jejuni and C. coli. Analysis of LOS gene content in 60 clinical C. jejuni isolates and 703 C. jejuni genome sequences revealed that class B (Group 1) was the most abundant LOS class in C. jejuni. The hierarchy of C. jejuni LOS group prevalence (group 1 > group 2 > group 3 > group 4) as well as the hierarchy of the frequency of C. jejuni LOS classes present within the group 1 (B > C > A > R > M > V), group 2 (H/P > O > E > W), group 3 (F > K > S) and group 4 (G > L) was identified. In silico analysis of LOS gene content in 564 C. coli genome sequences showed class III as the most abundant LOS locus type in C. coli. In silico analysis of LOS gene content also identified three novel LOS types of C. jejuni and previously unknown LOS biosynthesis genes in C. coli LOS locus types I, II, III, V and VIII. This study provides C. jejuni and C. coli LOS loci class frequencies in a smaller collection of C. jejuni clinical isolates as well as within the larger, worldwide database of C. jejuni and C. coli.

Consequences of Restricting Tramadol Dispensing in Iraqi Private Healthcare Facilities

Background and aim: Tramadol is a codeine analogue with less analgesic power than morphine but with better abuse potential. However, chronic use is associated with different adverse effects like anxiety, euphoria, nervousness, insomnia, depression, and agitation. In this study, we assessed the outcome behind the restriction on dispensing Tramadol in private health sectors in Iraq. Methods: We look at tramadol data from VigiBase data searches and the Individual Case Safety Reports (ICSR) that are formally supported by the WHO worldwide database. All complaints were evaluated using Vigilyze data mining and computing IC25 to assess the strength of the link between Tramadol and the adverse reactions it causes, as well as to compare them to other records from around the world. Results: For patients who used tramadol in a variety of dose forms, 184 instances were gathered over the course of seven years by the Iraqi Pharmacovigilance Center. There were 32 cases of hyperhidrosis, which occurred when tramadol was used alone, 47 incidents of vomiting, and 67 cases of nausea. Many adverse effects, including chest pain, hyperhidrosis, headache, dyspnea, and constipation, are more common in Iraqi records than in internationally known instances. Other side effects, such as vomiting, hallucination, vertigo, respiratory depression, and chills, were found to be milder than previously reported. There were no deaths in any of the instances that were recorded during this time period. Conclusion: The number of reported tramadol-induced adverse events has fallen significantly, which can be attributed to the ministry of health restricting tramadol dispensing and enabling public hospitals to only dispense it under medical monitoring.

The International Soil Moisture Network: serving Earth system science for over a decade

Abstract. In 2009, the International Soil Moisture Network (ISMN) was initiated as a community effort, funded by the European Space Agency, to serve as a centralised data hosting facility for globally available in situ soil moisture measurements (Dorigo et al., 2011b, a). The ISMN brings together in situ soil moisture measurements collected and freely shared by a multitude of organisations, harmonises them in terms of units and sampling rates, applies advanced quality control, and stores them in a database. Users can freely retrieve the data from this database through an online web portal (https://ismn.earth/en/, last access: 28 October 2021). Meanwhile, the ISMN has evolved into the primary in situ soil moisture reference database worldwide, as evidenced by more than 3000 active users and over 1000 scientific publications referencing the data sets provided by the network. As of July 2021, the ISMN now contains the data of 71 networks and 2842 stations located all over the globe, with a time period spanning from 1952 to the present. The number of networks and stations covered by the ISMN is still growing, and approximately 70 % of the data sets contained in the database continue to be updated on a regular or irregular basis. The main scope of this paper is to inform readers about the evolution of the ISMN over the past decade, including a description of network and data set updates and quality control procedures. A comprehensive review of the existing literature making use of ISMN data is also provided in order to identify current limitations in functionality and data usage and to shape priorities for the next decade of operations of this unique community-based data repository.

Circular Carbon Economy (CCE): A Way to Invest CO2 and Protect the Environment, a Review

Increased levels of carbon dioxide have revolutionised the Earth; higher temperatures, melting icecaps, and flooding are now more prevalent. Fortunately, renewable energy mitigates this problem by making up 20% of human energy needs. However, from a “green environment” perspective, can carbon dioxide emissions in the atmosphere be reduced and eliminated? The carbon economic circle is an ideal solution to this problem, as it enables us to store, use, and remove carbon dioxide. This research introduces the circular carbon economy (CCE) and addresses its economic importance. Additionally, the paper discusses carbon capture and storage (CCS), and the utilisation of CO2. Furthermore, it explains current technologies and their future applications on environmental impact, CO2 capture, utilisation, and storage (CCUS). Various opinions on the best way to achieve zero carbon emissions and on CO2 applications and their economic impact are also discussed. The circular carbon economy can be achieved through a highly transparent global administration that is supportive of advanced technologies that contribute to the efficient utilisation of energy sources. This global administration must also provide facilities to modernise and develop factories and power stations, based on emission-reducing technologies. Monitoring emissions in countries through a global monitoring network system, based on actual field measurements, linked to a worldwide database allows all stakeholders to track the change in greenhouse gas emissions. The process of sequestering carbon dioxide in the ocean is affected by the support for technologies and industries that adopt the principle of carbon recycling in order to maintain the balance. This includes supporting initiatives that contribute to increasing vegetation cover and preserving oceans from pollutants, especially chemicals and radioactive pollutants, which will undoubtedly affect the process of sequestering carbon dioxide in the oceans, and this will contribute significantly to maintaining carbon dioxide at acceptable levels.

Genotype-phenotype correlations in Marfan syndrome patients with FBN1 mutations: a cohort study on 1575 patients

Abstract Background Marfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype-phenotype correlations have been found in probands' studies only. Purpose The aim of this study is to provide survival curves and genotype-phenotype correlations in all patients with FBN1 mutations, probands and relatives. Methods We established survival curves and sought genotype–phenotype correlations in a population of 1575 consecutive MFS patients with pathogenic class 4 or 5 variants in the FBN1 gene. This population represents the most comprehensive clinical database worldwide on MFS. Results Global survival was 90% at 60 years. However, lifelong aortic event rate (either dissection or surgery) and survival were impacted by the genotype. Premature termination codons (PTC), resulting in haploinsufficiency, were associated with a shorter life expectancy and a high lifelong risk of an aortic event (83%). Interestingly, these variants were also associated with the highest risk of severe scoliosis (52%) and with a lower risk for ectopia lentis (EL) surgery (13%). Dominant negative in-frame pathogenic variants could be subdivided according to their impact on the cysteine content of fibrillin-1: cysteine loss (–Cys) was associated with high aortic risk (73%) and a higher frequency of EL surgery (43%); cysteine addition was associated with moderate aortic risk (29%) and the highest frequency of EL surgery (48%); unchanged cysteine content was associated with high aortic risk (61%) and lower frequency of EL surgery (23%). No gene-region effect was observed, except for a more severe phenotype for in-frame variants with cysteine loss within the “neonatal region”. Aortic risk was greater for males in all subgroups, and probands were more severely affected. Conclusions MFS genotype-phenotype correlations related to pathogenic FBN1 variants exist for aortic and extra-aortic features. This leads us to propose new tools to refine the prognosis in this population. Preventive therapy with β-blockers and restricted exercise should be proposed regardless of the aortic diameter in the high aortic risk groups (PTC and –Cys variants). These results have major consequences on genetic counseling and personalized medicine for patients carrying a FBN1 mutation. This study also improves the overall understanding of the role of FBN1 in various organs. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Fondation Coeur et Recherche, Paris, FranceFédération Française de Cardiologie, Paris, France Patients with PTC vs. in-frame mutationsDifferences within in-frame mutations

The Global Automotive Industry Stock Returns During the COVID-19 Pandemic

This study analyzes the relationship of firm-level ESG scores and stock returns from a worldwide database for the automotive industry. It measures the significance of the ESG and CFP relationship during the last decade, and includes a comparison of those firms with different levels of ESG scores, as well as between firms with ESG scores and to firms that lack such scores. A quasi-experimental difference-in-differences (DID) design and a panel data are estimated to examine the impact of ESG scores and ESG combined scores on firms’ stock return before and during the COVID-19 pandemic period. The results suggest that sustainable actions during the pandemic lessened stock returns, as evidenced by the negative coefficients of the ESGC and ESG scores. The interaction terms with firm size, revealed that ESGC and ESG scores had a positive relationship with stock returns during the pandemic. Thus, larger firms’ returns benefited from higher ESG scores during the COVID-19 crisis. The performance of the stratified sample firms’ stock returns in the context of the COVID-19 sanitary emergency is an original contribution to the literature on the ESG-CFP relationship.

A Human Pleiotropic Multiorgan Condition Caused by Deficient Wnt Secretion

BackgroundStructural birth defects occur in approximately 3% of live births; most such defects lack defined genetic or environmental causes. Despite advances in surgical approaches, pharmacologic prevention remains largely out of reach.MethodsWe queried worldwide databases of 20,248 families that included children with neurodevelopmental disorders and that were enriched for parental consanguinity. Approximately one third of affected children in these families presented with structural birth defects or microcephaly. We performed exome or genome sequencing of samples obtained from the children, their parents, or both to identify genes with biallelic pathogenic or likely pathogenic mutations present in more than one family. After identifying disease-causing variants, we generated two mouse models, each with a pathogenic variant “knocked in,” to study mechanisms and test candidate treatments. We administered a small-molecule Wnt agonist to pregnant animals and assessed their offspring.ResultsWe identified homozygous mutations in WLS, which encodes the Wnt ligand secretion mediator (also known as Wntless or WLS) in 10 affected persons from 5 unrelated families. (The Wnt ligand secretion mediator is essential for the secretion of all Wnt proteins.) Patients had multiorgan defects, including microcephaly and facial dysmorphism as well as foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects. The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis. Administration of a pharmacologic Wnt agonist partially restored embryonic development.ConclusionsGenetic variations affecting a central Wnt regulator caused syndromic structural birth defects. Results from mouse models suggest that what we have named Zaki syndrome is a potentially preventable disorder. (Funded by the National Institutes of Health and others.)

Hybrid Simulation of Near-Fault Ground Motion for a Potential Mw 7 Earthquake in Lebanon

ABSTRACTLebanon is a densely populated country crossed by major faults. Historical seismicity shows the potential of earthquakes with magnitudes >7, but large earthquakes have never been instrumentally recorded in Lebanon. Here, we propose a method to simulate near-fault broadband ground motions for a potential Mw 7 earthquake on the Yammouneh fault (YF)—the largest branch of the Dead Sea Transform fault that bisects Lebanon from north to south. First, we performed the first 3D tomography study of Lebanon using ambient noise correlation, which showed that Lebanon could be approximated by a 1D velocity structure for low-frequency (LF) ground-motion simulation purposes. Second, we generated suites of kinematic rupture models on the YF, accounting for heterogeneity of the rupture process, and uncertainty of the rupture velocity and hypocenter location. The radiated seismic energy was next propagated in the inferred 1D velocity model to obtain suites of LF ground motions (<1 Hz) at four hypothetical near-fault seismic stations. These LF simulations included the main features of near-fault ground motions, such as the impulsive character of ground velocity due to the rupture directivity or fling-step effects (so-called pulse-like ground motions). Third, to obtain broadband ground motions (up to 10 Hz), we proposed a hybrid technique that combined the simulated LF ground motions with high-frequency (HF) stochastic simulations, which were empirically calibrated using a worldwide database of near-fault recordings. Contrary to other hybrid approaches, in which the LF and HF motions are generally computed independently, the characteristics of stochastic HF ground motions were conditioned on those of LF ground motions (namely on the characteristics of the velocity pulse, if it existed, or on the absence of a pulse). The simulated peak ground accelerations were in agreement with the ones reported in the Next Generation Attenuation-West2 (NGA-West2) database for similar magnitude and distances and with three NGA-West2 ground-motion prediction equations.

MLVA typing of Brucella melitensis and B. abortus isolates of animal and human origin from India

Brucellosis is a widely prevalent zoonotic disease of major public health significance. A collection of Brucella melitensis and Brucella abortus field isolates of animal and human origin were subjected to MLVA-15 typing followed by phylogeography studies. The MLVA-15 analysis of B. melitensis (n = 65) field isolates resulted in 48 different profiles. The panel I marker bruce45 was found to be most conserved, while the rest of the panel I markers showed low to moderate length polymorphism. Among the panel II markers, bruce04, bruce16 and bruce30 showed a high discriminatory index. The MLVA-15 typing of 13 B. abortus field isolates revealed 13 different genotypes with panel II markers showing higher discriminatory ability vis-à-vis panel I. The minimum spanning tree analysis (MST) in comparison with isolates from the international database revealed that all B. melitensis and B. abortus isolates from this study belonged to the ‘Eastern Mediterranean’ and the ‘abortus C’ lineage, respectively. The MLVA-15 typing could differentiate field isolates of B. abortus and B. melitensis originating from different regions, reaffirming the technique’s potential of high resolution and suitability for local epidemiological studies. The MLVA scheme also has the advantage of comparison of local isolates with a worldwide database, allowing for phylogeographical studies.

A comparative study of India and Australia open access repositories in open DOAR

An open access repository or open archive is a digital platform that holds research output and provides free, immediate and permanent access to research results for anyone to use, download and distribute. To facilitate open access such repositories must be interoperable according to the Open Archives Initiative Protocol for Metadata Harvesting (OAI-PMH). Search engines harvest the content of open access repositories, constructing a database of worldwide, free of charge available research. OpenDOAR is the quality-assured, global Directory of Open Access Repositories. Its repositories provide free, open access to academic outputs and resources. This paper deals with Comparative analysis of India and Australia repositories listed in OpenDOAR in terms of their growth, type, operational status, content type, software, subject coverage, language and policies regarding content, submission, and preservation. Keywords: Digital Repositories, Institutional Repositories, Open Access, OpenDOAR.

Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

PurposeMarfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype–phenotype correlations have been found in proband studies only. MethodsIn 1,575 consecutive MFS probands and relatives from the most comprehensive database worldwide, we established survival curves and sought genotype–phenotype correlations. ResultsA risk chart could be established with clinical and genetic data. Premature termination codon variants were not only associated with a shorter life expectancy and a high lifelong risk of aortic event, but also with the highest risk of severe scoliosis and a lower risk for ectopia lentis (EL) surgery. In-frame variants could be subdivided according to their impact on the cysteine content of fibrillin-1 with a global higher severity for cysteine loss variants and the highest frequency of EL surgery for cysteine addition variants. ConclusionThis study shows that FBN1 genotype–phenotype correlations exist for both aortic and extra-aortic features. It can be used for optimal risk stratification of patients with a great importance for genetic counseling and personalized medicine. This also provides additional data for the overall understanding of the role of fibrillin-1 in various organs.

626-P: Intermittently Scanned Continuous Glucose Monitoring Data of Polish Patients from Real-Life Conditions: More Scanning and Better Glycemic Control than Worldwide

Randomized trials and observational studies have shown that the use of FreeStyle Libre® intermittently-scanned CGMS was associated with improved glycemic indices such as HbA1c, TIR (70-180 mg/dl), TBR (<70 mg/dl) or TAR (>180 mg/dl), and improved quality of life. In this RWD analysis, we aimed to describe glucometrics among FreeStyle Libre users from Poland and compare them with international data. The analyzed time period for the Polish and worldwide users ranged from August 2016, September 2014, respectively, to August 2020. Data from the Polish population was collected from 10,679 readers and 92,627 sensors with 22.3 million glucose scans and 113 million automatically-recorded glucose readings, while the worldwide database included information from 981,876 readers and 11,179,229 sensors with 13.1 billion glucose readings. On average, the Polish users of isCGM performed substantially more scans/day (21.2±14.2 vs. 13.2±10.7), were characterized by considerably lower eHbA1c (7.0±1.2% vs. 7.5±1.5%), spent more TIR (64.2±17.3% vs. 58.1±20.3%) and less TAR (29.7±18.0% vs. 36.6±21.3%) (p<0.0001 for all comparisons). Moreover, Polish users were more likely to achieve TIR>70% (36.3% vs. 28.8%). Our results confirmed earlier findings that analyzed glucometrics improve as scan rate frequency increases; however, additional analyses showed that at the same scanning frequency, Polish users achieved lower eHbA1c, higher TIR, lower TAR, but higher TBR than the comparative group. In summary, we report more scanning and better glycemic control in Polish isCGM users than worldwide. Due to the nature of this study, we are not able to explain the cause of this observation. It could be associated with demographic characteristics, such as a higher proportion of adult users, or more efficient diabetes education. Our data seems to suggest more frequent scanning than currently recommended. Disclosure J. Hohendorff: Advisory Panel; Self; Abbott, Roche Diabetes Care, Other Relationship; Self; Merck & Co., Inc., Polfa Tarchomin S. A. J. Gumprecht: Advisory Panel; Self; Abbott, Research Support; Self; Bayer AG, Merck & Co., Inc., Speaker’s Bureau; Self; AstraZeneca, Bioton S. A., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S, Sanofi. M. Mysliwiec: None. D. Zozulinska-ziolkiewicz: None. M. Malecki: Advisory Panel; Self; Abbott Diabetes, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck & Co., Inc., Mundipharma International, Novo Nordisk, Sanofi-Aventis, Servier Laboratories.

Crystal structure analysis and fragmentation profile of lorcaserin hydrochloride hemihydrate

Lorcaserin, a 2,3,4,5-tetrahydro-3-benzazepine possessing a methyl and chloro groups in C-4 and C-9, respectively, is a drug currently used to treat obesity. Considering the role of the crystalline state to the understanding of the drug properties, allied to inexistence of solid state structural data in the worldwide accessible literature and database such as Crystallographic Cambridge Data Centre (CCDC), here we report the crystal structure of lorcaserin hydrochloride hemihydrate, inspecting in full detail its intra and intermolecular features for the first time, together with NMR data and fragmentation profile by ESI(+)-MS/MS.

The Analysis of Global COVID-19 Clinical Trials Registries

Background: Corona Virus Disease 2019 (COVID-19) is a pandemic-associated health emergency. Multiple preventive strategies have been implemented to try to prevent its transmission, and no drugs have proven to be highly effective yet. There are many ongoing clinical studies of COVID-19 and the information is scattered in each country’s own database. Objective: To provide the insight of the ongoing COVID-19 studies and present the database information to researchers. Healthcare provider can follow these COVID-19 studies and prepare for the upcoming second wave. Materials and Methods: The authors’ searched all COVID-19 studies that were listed in clinical trial registries worldwide and extracted information from each study. The authors’ reported these studies including study population, type of study, country of origin, treatment assigned in controlled clinical trials, and matched the date of registration to the real-world cases. Results: Two thousand nine hundred forty-nine studies from 18 registries were found. Over 2,000 (2,224) studies (75.4%) targeted symptomatic COVID-19 patients, 387 studies (13.1%) targeted non-infected general population, and 237 studies (8.1%) included healthcare personnel. Clinical controlled trials were found in 1,491 studies (50.6%) and 1,346 studies (45.6%) were observational studies. ClinicalTrials.gov was the most prevalent registry, followed by Chinese Clinical Trial Registry (ChiCTR). China also had the highest number of registered trials. Antimalarials and antivirals were the most frequently used treatments in the controlled trials. The number of trials registered increased in parallel to the total number of real-world cases. Conclusion: The number of ongoing COVID-19 clinical trials are steadily increasing. The present study provides an overview of registered studies from worldwide databases, which researchers can use to plan and conduct future studies. Keywords: COVID-19, Clinical trial registry, Global trend

A predictive equation for residual strength using a hybrid of subset selection of maximum dissimilarity method with Pareto optimal multi-gene genetic programming

More accurate and reliable estimation of residual strength friction angle (ϕr) of clay is crucial in many geotechnical engineering applications, including riverbank stability analysis, design, and assessment of earthen dam slope stabilities. However, a general predictive equation for ϕr, with applicability in a wide range of effective parameters, remains an important research gap. The goal of this study is to develop a more accurate equation for ϕr using the Pareto Optimal Multi-gene Genetic Programming (POMGGP) approach by evaluating a comprehensive dataset of 290 experiments compiled from published literature databases worldwide. A new framework for integrated equation derivation proposed that hybridizes the Subset Selection of Maximum Dissimilarity Method (SSMD) with Multi-gene Genetic Programming (MGP) and Pareto-optimality (PO) to find an accurate equation for ϕr with wide range applicability. The final predictive equation resulted from POMGGP modeling was assessed in comparison with some previously published machine learning-based equations using statistical error analysis criteria, Taylor diagram, revised discrepancy ratio (RDR), and scatter plots. Base on the results, the POMGGP has the lowest uncertainty with U95 = 2.25, when compared with Artificial Neural Network (ANN) (U95 = 2.3), Bayesian Regularization Neural Network (BRNN) (U95 = 2.94), Levenberg-Marquardt Neural Network (LMNN) (U95 = 3.3), and Differential Evolution Neural Network (DENN) (U95 = 2.37). The more reliable results in estimation of ϕr derived by POMGGP with reliability 59.3%, and resiliency 60% in comparison with ANN (reliability = 30.23%, resiliency = 28.33%), BRNN (reliability = 10.47%, resiliency = 10.39%), LMNN (reliability = 19.77%, resiliency = 20.29%) and DENN (reliability = 27.91%, resiliency = 24.19%). Besides the simplicity and ease of application of the new POMGGP equation to a broad range of conditions, using the uncertainty, reliability, and resilience analysis confirmed that the derived equation for ϕr significantly outperformed other existing machine learning methods, including the ANN, BRNN, LMNN, and DENN equations.

Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

Marfan syndrome (MFS) is a connective tissue disorder in which several systems, including cardiovascular, ophthalmological and skeletal systems, are affected with great phenotypic variability. Although known to be associated with FBN1 mutations, only few genotype-phenotype correlations have been found in probands’ studies only. The clinical variability and unpredictability remain limiting factors for personalized follow-up and effective genetic counseling. The aim of this study was to provide genotype-phenotype correlations in MFS patients with FBN1 mutations. In 1575 consecutive MFS probands and relatives from the most comprehensive database worldwide with mutations in the FBN1 gene, we established survival curves and sought genotype-phenotype correlations. A risk chart could be established with clinical and genetic data. The aortic risk was greater for males, and probands were more severely affected than relatives as generally agreed. Global survival was 90% at 60 years. However, lifelong aortic event rate (either dissection or surgery) and survival were impacted by the genotype. Premature termination codon variants were not only associated with a shorter life expectancy, a high lifelong risk of aortic event (83%), but also with the highest risk of severe scoliosis (52%) and a lower risk for ectopia lentis (EL) surgery (13%). In-frame variants could be subdivided according to their impact on the cysteine content of fibrillin-1 with a global higher severity for cysteine loss variants and the highest frequency of EL surgery for cysteine addition variants (48%) ( Fig. 1 ). This study shows that FBN1 genotype–phenotype correlations exist for both aortic and extra-aortic features. It can be used for optimal risk stratification of patients with a great importance for genetic counseling and personalized medicine. This also provides additional data for the overall understanding of the role of fibrillin-1 in various organs.

Intermittently Scanned Continuous Glucose Monitoring Data of Polish Patients from Real-Life Conditions: More Scanning and Better Glycemic Control Compared to Worldwide Data.

Background: Randomized trials and observational studies have shown that the use of FreeStyle Libre® intermittently scanned continuous glucose monitoring system (isCGMS) is associated with improved glycemic indices and quality of life.Materials and Methods: In this retrospective, real-world data analysis, we described country-specific glucometrics among isCGMS users from Poland and compared them with international data. The analyzed time period for the Polish data ranged between August 2016 and August 2020, and the analyzed time period for the international data ranged from September 2014 to August 2020.Results: Data from the Polish population were collected from 10,679 readers and 92,627 sensors with 113 million automatically recorded glucose readings. The worldwide database included information from 981,876 readers and 11,179,229 sensors with 13.1 billion glucose readings. On average, the users of isCGMS from Poland performed substantially more scans/day (21.2 ± 14.2 vs. 13.2 ± 10.7), achieved lower eHbA1c (7.0% ± 1.2% vs. 7.5% ± 1.5%), and spent more time-in-range (TIR) (64.2% ± 17.3% vs. 58.1% ± 20.3%) and less time-above-range (TAR) (29.7% ± 18.0% vs. 36.6% ± 21.3%) (P < 0.0001 for all comparisons). Moreover, they were more likely to achieve TIR >70% (36.3% vs. 28.8%), but spent more time-below-range (TBR) (4.7% vs. 3.6%). Our results confirmed that analyzed glucometrics improve as the scan rate frequency increases. However, at a similar scanning frequency to the comparative group, users from Poland achieved lower eHbA1c, higher TIR, and lower TAR, but higher TBR.Conclusions: We report more scanning and better glycemic control in isCGMS users in Poland than worldwide. The cause of this observation remains unknown. Our data also show that in real-life practice, a large number of patients may be willing to perform scanning more frequently than it is usually assumed.

The Benefits of Combining Global and Local Data—A Showcase for Valuation and Mapping of Mangrove Climate Regulation and Food Provisioning Services within a Protected Area in Pará, North Brazil

Mangrove forests provide a large variety of ecosystem services (ES) to coastal societies. Using a case study focusing on the Ajuruteua peninsula in Northern Brazil and two ES, food provisioning (ES1) and global climate regulation (ES2), this paper proposes a new framework for quantifying and valuing mangrove ES and allow for their small-scale mapping. We modelled and spatialised the two ES from different perspectives, the demand (ES1) and the supply (ES2) side respectively. This was performed by combining worldwide databases related to the global human population (ES1) or mangrove distribution and canopy height (ES2) with locally derived parameters, such as crab catches (ES1) or species-specific allometric equations based on local estimates of tree structural parameters (ES2). Based on this approach, we could estimate that the area delivers the basic nutrition of about 1400 households, which equals 2.7 million USD, and that the mangrove biomass in the area contains 2.1 million Mg C, amounting to 50.9 million USD, if it were paid as certificates. In addition to those figures, we provide high-resolution maps showing which areas are more valuable for the two respective ES, information that could help inform management strategies in the future.

Government choice between contract termination and contract expiration in re-municipalization: a case of historical recurrence?

Since the early 2000s, the terms ‘re-municipalization’ and ‘reverse privatization’ entered the lexicon as several examples emerged of governments taking ownership of assets and services that had previously been privatized or outsourced. Various methods are used to implement re-municipalization decisions and differences are observed across countries and sectors. The approaches most frequently adopted are re-municipalization through contract termination and contract expiration. We utilize a wide database of re-municipalizations worldwide to analyse the factors that influence governments’ choice between these two approaches. The results from our multivariate analysis find a pattern of historical recurrence in the characteristics of the current re-municipalization process. Points for practitioners Most governments wait for contracts to expire but the number of contract terminations is sizeable. Re-municipalization in larger cities, network sectors (particularly water) and implemented by municipal governments have a positive association with termination. Re-municipalization of energy utilities and conducted in countries of French legal origin is positively associated with contract expiration. Patterns of contemporary re-municipalization closely resemble those witnessed in the ‘Progressive Era’.