Reference Network Research Articles

The first absolute gravity and height reference network in Sicily

The purpose of this work is to provide the methodological and instrumental framework for the establishment of a new absolute gravity and height reference network in Sicily. The aim of the network is to contribute to the new reference systems in the Italian area, useful for the scientific and technological activities related to the gravity field and to the proper definition of a modern height system in this region. The network is composed of 5 stations, evenly distributed to form a large mesh, which roughly covers the entire Sicily. Since four of the five selected stations were measured also in the 1990s, it was also possible to evaluate whether long-term gravity changes occurred at these sites (basic requirement for a reference network) and check the long-term ground deformation patterns, using data from the closest GPS/GNSS stations. The observed gravity changes over a time interval of about 30 years at the absolute stations and in the surrounding areas, confirm the long-term stability of the selected areas/sites.

Learning from conect4children: A Collaborative Approach towards Standardisation of Disease-Specific Paediatric Research Data

The conect4children (c4c) initiative was established to facilitate the development of new drugs and other therapies for paediatric patients. It is widely recognised that there are not enough medicines tested for all relevant ages of the paediatric population. To overcome this, it is imperative that clinical data from different sources are interoperable and can be pooled for larger post hoc studies. c4c has collaborated with the Clinical Data Interchange Standards Consortium (CDISC) to develop cross-cutting data resources that build on existing CDISC standards in an effort to standardise paediatric data. The natural next step was an extension to disease-specific data items. c4c brought together several existing initiatives and resources relevant to disease-specific data and analysed their use for standardising disease-specific data in clinical trials. Several case studies that combined disease-specific data from multiple trials have demonstrated the need for disease-specific data standardisation. We identified three relevant initiatives. These include European Reference Networks, European Joint Programme on Rare Diseases, and Pistoia Alliance. Other resources reviewed were National Cancer Institute Enterprise Vocabulary Services, CDISC standards, pharmaceutical company-specific data dictionaries, Human Phenotype Ontology, Phenopackets, Unified Registry for Inherited Metabolic Disorders, Orphacodes, Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), and Observational Medical Outcomes Partnership. The collaborative partners associated with these resources were also reviewed briefly. A plan of action focussed on collaboration was generated for standardising disease-specific paediatric clinical trial data. A paediatric data standards multistakeholder and multi-project user group was established to guide the remaining actions—FAIRification of metadata, a Phenopackets pilot with RDCA-DAP, applying Orphacodes to case report forms of clinical trials, introducing CDISC standards into European Reference Networks, testing of the CDISC Pediatric User Guide using data from the mentioned resources and organisation of further workshops and educational materials.

Introducing re-weighted range voting in clinical practice guideline prioritization: Development and testing of the re-weighted priority-setting (REPS) tool.

We aimed to develop and test a tool based on the re-weighted range voting mechanism to prioritize items (i.e. key questions) in a priority-setting assessment for clinical practice guidelines. The secondary aim was to provide methodological context of the tool. We iteratively developed the tool and used qualitative methods (i.e. think-aloud and semi-structured interviews) to test the tool's usability and make adjustments accordingly. An observational approach was used to test the tool's outcome satisfaction in a real-world priority-setting assessment within a rare-disease guideline of a European Reference Network and under four different conditions in the tool. Four guideline methodologists tested the usability of the tool. The real-world testing was performed with a guideline panel consisting of a core working group, five expertise working groups, and a working group with patient representatives. Thirty-one panel members assigned scores in the priority-setting assessment. Seventeen panel members rated the priority-setting outcome, and sixteen panel members rated the outputs generated under the four conditions. Upon initial use, guideline methodologists found the tool to be quite overwhelming. However, with some initial effort they were able to easily identify the tool's structure. Based on observations and feedback, the tool was further refined and user guidance was developed. Guideline panel members expressed (high) satisfaction with the priority-setting outcome. They particularly preferred the condition when using mean subgroup scores as input or employing aggressive penalties in the weighting method to determine the outputs. The tool generates a ranked list of items and offers flexibility for different choices in priority-setting assessments as long as its input format requirements are met. Although it is not a consensus method, the tool assists in narrowing down a set of priority items. Additional steps in the priority-setting assessment can lead to a consensus being reached regarding the final outcome.

Considerable differences in management of cytomegalovirus infection in patients with biliary atresia

AbstractObjectivesPatients with biliary atresia (BA) and ongoing cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy than uninfected patients. Still, there is no consensus on the usefulness of viral testing and antiviral treatment (AVT). This study aims to explore the need for future research on AVT for CMV infection by assessing how CMV infection in BA patients is managed in different centers.MethodsAn online questionnaire with 10 questions was offered to participants at an international congress on BA, organized in collaboration with the European Reference Network (ERN) for rare liver diseases in 2022. Answers to questions were either dichotomic or multiple choices of different numeric intervals. Ongoing CMV infection was defined by detecting CMV‐IgM in serum or CMV‐DNA by PCR in blood or urine.ResultsThere were 43 respondents from 36 centers in 26 countries. The total number of BA patients per year was between 208 and 380 from centers with 0–5 to >20 BA patients yearly (median 6–10). CMV infection was tested in 27 centers (75%), of which 18 (67%) use AVT. The rate of CMV infection varied between 0%–5% and 40%–50% (median 5%–10%). Willingness to treat the infection did not differ between centers with low and high rates of CMV infection.ConclusionsMost centers test for CMV infection, and a considerable proportion use AVT despite the lack of evidence of its benefits. A future randomized study on treating CMV infection in BA patients is necessary and feasible.

Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group.

Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy. A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement. A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ-aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted. These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug-related adverse events in individuals living with PMD-related epilepsy.

Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey.

Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). To evaluate current management of new cases of CS with a focus on VTE and thromboprophylaxis. A survey was conducted within those that report in electronic reporting tool (e-REC) of The European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 until July 2022. Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%) and 12 patients ectopic CS (5.4%). The mean follow-up period post CS diagnosis was 15 months (range 3-30). Cortisol lowering medications were initiated in 38% of patients. One hundred and fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular weight-heparins were used in 96% of cases. VTE was reported in 6 patients (2.7%), of which 1 was fatal: 2 long before CS diagnosis, 2 between diagnosis and surgery and 2 post-operatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage and half of the VTE cases even occurred during this stage despite thromboprophylaxis Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed.

Half a Century of Research on Posttraumatic Stress Disorder: A Scientometric Analysis.

We conducted a scientometric analysis to outline clinical research on posttraumatic stress disorder (PTSD). Our primary objective was to perform a broad-ranging scientometric analysis to evaluate key themes and trends over the past decades. Our secondary objective was to measure research network performance. We conducted a systematic search in the Web of Science Core Collection up to 15 August 2022 for publications on PTSD. We identified 42,170 publications published between 1945 and 2022. We used CiteSpace to retrieve the co-cited reference network (1978-2022) that presented significant modularity and mean silhouette scores, indicating highly credible clusters (Q = 0.915, S = 0.795). Four major trends of research were identified: 'war veterans and refugees', 'treatment of PTSD/neuroimaging', 'evidence syntheses', and 'somatic symptoms of PTSD'. The largest cluster of research concerned evidence synthesis for genetic predisposition and environmental exposures leading to PTSD occurrence. Research on war-related trauma has shifted from battlefield-related in-person exposure trauma to drone operator trauma and is being out published by civilian-related trauma research, such as the 'COVID-19' pandemic impact, 'postpartum', and 'grief disorder'. The focus on the most recent trends in the research revealed a burst in the 'treatment of PTSD' with the development of Mhealth, virtual reality, and psychedelic drugs. The collaboration networks reveal a central place for the USA research network, and although relatively isolated, a recent surge of publications from China was found. Compared to other psychiatric disorders, we found a lack of high-quality randomized controlled trials for pharmacological and nonpharmacological treatments. These results can inform funding agencies and future research.

Familial hyperaldosteronism: an European Reference Network on Rare Endocrine Conditions clinical practice guideline.

We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant.

Estimation of BDS-2/3 phase observable-specific signal bias aided by double-differenced model: an exploration of fast BDS-2/3 real-time PPP

GNSS phase observable-specific signal bias (OSB) corrections are essential for widespread application of precise point positioning with ambiguity resolution (PPP-AR) or PPP-RTK. However, subject to the orbital error effects, conventional undifferenced (UD) model-derived BeiDou System (BDS) real-time (RT) OSB products are usually unsatisfactory. In this study, a novel OSB-generating method assisted by the double-differenced (DD) model is proposed. The reliable integer UD ambiguities are obtained by converting DD ambiguities with given ambiguity datums, by which the RT orbit error effects on ambiguity fixing can be reduced during the OSB extraction and PPP-AR process. Validated using data from two regional sparse GNSS reference networks in Shaanxi, China, and Europe, results show that the proposed method-derived OSB products can improve RT PPP-AR performance effectively. In the Shaanxi network, the narrow-lane ambiguity residuals for BDS-3 within ± 0.25 cycles are improved by 23.1% and 33.2% compared to those using the UD model and Centre National d’Etudes Spatiales (CNES)-derived OSB products, respectively, and the corresponding values are 15.2% and 43.1% in the European network. A centimeter- or even millimeter-level positioning accuracy can be achieved for BDS PPP using the poposed OSB products in both networks. In the kinematic PPP-AR test within the Shanxi network, the mean RMS of the BDS-2/3 fixed solutions in the east, north, and up directions is 0.9, 0.7, and 2.3 cm, with a decrease of 57.1%, 53.3%, and 46.5% compared to that using OSB derived by UD model. The median Time-To-First-Fix (TTFF) is also shortened from 23.8 to 7.5 min.

Accessibility, availability and common practices regarding genetic testing for epilepsy across Europe: A survey of the European Reference Network EpiCARE.

The increasingly rapid pace of advancement in genetic testing may lead to inequalities in technical and human resources with a negative impact on optimal epilepsy clinical practice. In this view, the European Reference Network (ERN) for Rare and Complex Epilepsies EpiCARE conducted a survey addressing several aspects of accessibility, availability, costs, and standard practices on genetic testing across ERN EpiCARE centers. An online Google form was sent to 70 representatives of ERN EpiCARE centers. Descriptive statistics and qualitative analysis were used for data presentation. We received 45 responses (1/center) representing 23 European countries with a better representation of Western Europe. Forty-five percent of the centers did not have access to all available types of genetic testing, mainly reflecting the limited availability of whole-genome sequencing (WGS). Thirty-five percent of centers report cost coverage only for some of the available tests, while costs per test varied significantly (interquartile range IQR ranging from 150 to 1173 euros per test across centers). Urgent genetic testing is available in 71.7% of countries (time-to-urgent result: 2 day to 2 months). The average time-to-result of specific tests in case of non-urgent prescription has a significant variance across centers, with the biggest range observed for whole-exome sequencing (6-128 weeks, IQR: 27 weeks). The percentage of agreement among the experts regarding the choice of genetic test at first intention in specific clinical situations was in all cases less than 50 percent (34.9% to 47% according to the proposed scenarios). Costs, time to deliver the results to the clinician, and type of first-line genetic testing vary widely across Europe, even in countries where ERN EpiCARE centers are present. Increased availability of genetic tests and guidance for optimal test choices in epilepsy remains essential to avoid diagnostic delays and excess health costs. The survey of the ERN EpiCARE highlights disparities in genetic testing for epilepsy across 45 ERN EpiCARE centers in 23 European countries. The findings reveal variable access to certain genetic tests, with lowest access to WGS. Costs and time-to-results vary widely. Urgent genetic testing is available in 71.7% of countries. Agreement among experts on first-line genetic tests for specific patient scenarios is below 50%. The study emphasizes the need for improved test availability and guidance to avoid diagnostic delays and unnecessary costs. EpiCARE has the mission to contribute in homogenizing best practices across Europe.

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).

This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available. A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management. This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

On the Capacity of Optical Backbone Networks

Optical backbone networks, characterized by using optical fibers as a transmission medium, constitute the fundamental infrastructure employed today by network operators to deliver services to users. As network capacity is one of the key factors influencing optical network performance, it is important to comprehend its limitations and have the capability to estimate its value. In this context, we revisit the concept of capacity from various perspectives, including channel capacity, link capacity, and network capacity, thus providing an integrated view of the problem within the framework of the backbone tier. Hence, we review the fundamental concepts behind optical networks, along with the basic physical phenomena present in optical fiber transmission, and provide methodologies for estimating the different types of capacities, mainly using simple formulations. In particular, we propose a method to evaluate the network capacity that relies on the optical reach to account for physical layer aspects, in conjunction with capacitated routing techniques for traffic routing. We apply this method to three reference networks and obtain capacities ranging from tens to hundreds of terabits/s. Whenever possible, we also compare our results with published experimental data to understand how they relate.

FOXG1 variants can be associated with milder phenotypes than congenital Rett syndrome with unassisted walking and language development.

Since 2008, FOXG1 haploinsufficiency has been linked to a severe neurodevelopmental phenotype resembling Rett syndrome but with earlier onset. Most patients are unable to sit, walk, or speak. For years, FOXG1 sequencing was only prescribed in such severe cases, limiting insight into the full clinical spectrum associated with this gene. Next-generation sequencing (NGS) now enables unbiased diagnostics. Through the European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders, we gathered data from patients with heterozygous FOXG1 variants presenting a mild phenotype, defined as able to speak and walk independently. We also reviewed data from three previously reported patients meeting our criteria. We identified five new patients with pathogenic FOXG1 missense variants, primarily in the forkhead domain, showing varying nonspecific intellectual disability and developmental delay. These features are not typical of congenital Rett syndrome and were rarely associated with microcephaly and epilepsy. Our findings are consistent with a previous genotype-phenotype analysis by Mitter et al. suggesting the delineation of five different FOXG1 genotype groups. Milder phenotypes were associated with missense variants in the forkhead domain. This information may facilitate prognostic assessments in children carrying a FOXG1 variant and improve the interpretation of new variants identified with genomic sequencing.

[Treatment of autoimmune hepatitis-First-line, second-line and third-line treatment].

Autoimmune hepatitis (AIH) is a rare autoimmune inflammation of the liver mostly with a chronic course, which can also be acutely manifested up to acute liver failure. It affects women 3-4 times more frequently than men and can be diagnosed in all age groups. In one third of the patients a liver cirrhosis is present at the time of diagnosis. It is characterized by a hepatic inflammation pattern, a polyclonal hypergammaglobulinemia of immunoglobulin G and the detection of autoantibodies. A liver biopsy is necessary to make the diagnosis. The AIH is histologically characterized in particular by a lymphoplasmacytic infiltrate in the portal fields. In cases with a relevant disease activity, AIH is typically treated by immunosuppression. The immunosuppressive treatment is associated with a prevention of disease progression to liver cirrhosis and a better survival. The success of treatment is measured by achieving biochemical remission, i.e., normalization of the transaminase and immunoglobulin G levels as a good noninvasive predictor of a histological remission. Another treatment target is an improvement of the symptoms of the patient. The first-line treatment consists of a glucocorticoid, mostly prednisolone or in cases without advanced fibrosis budesonide, and azothioprine. For reduction of steroid-specific treatment side effects the maintenance treatment should be carried out steroid-free whenever possible. In cases of insufficient response to azothioprine or side effects a treatment attempt using antimetabolites, such as 6‑mercaptopurine or mycophenolate mofetil is primarily carried out as second-line treatment. For patients who do not achieve biochemical remission through first-line or second-line treatment, a variety of medications are available for third-line treatment, e.g., rituximab, calcineurin inhibitors or antitumor necrosis factor (anti-TNF) antibodies. Third-line treatment should be carried out in expert centers and registered in the European Reference Network for Rare Liver Diseases in order to improve the currently sparse database for these forms of treatment in the future.

Bayesian analysis of the detection performance of the Lightning Imaging Sensors

Abstract Identical Lightning Imaging Sensors aboard the Tropical Rainfall Measuring Mission satellite (TRMM LIS, 1998–2015) and International Space Station (ISS LIS, 2017–present) have provided over two decades of lightning observations over the global tropics, with ISS LIS extending coverage into the mid-latitudes. Quantifying the detection performance of both LIS sensors is a necessary step toward generating a combined LIS climatological record and accurately combining LIS data with lightning detections from other sensors and networks. We compare lightning observations from both LIS sensors with reference sources including the Geostationary Lightning Mapper (GLM) and ground-based Earth Networks Total Lightning Network (ENTLN), Earth Networks Global Lightning Network (ENGLN), National Lightning Detection Network (NLDN), and Global Lightning Dataset (GLD360). Instead of a relative detection efficiency (DE) approach that assumes perfect performance of the reference sensor, we employ a Bayesian approach to estimate the upper limit of the absolute DE (ADE) of each system being analyzed. The results of this analysis illustrate the geographical pattern of ADE as well as its diurnal cycle and yearly evolution. Reference network ADE increased by ~15–30% during the TRMM era, leading to a decline in TRMM LIS ADE. ISS LIS flash ADE has been relatively consistent at 61–65%, about 4–5% lower than TRMM LIS at the end of its lifetime.

Accurate Identification Method of Small-Size Polymetallic Nodules Based on Seafloor Hyperspectral Data

Polymetallic nodules are spherical or ellipsoidal mineral aggregates formed naturally in deep-sea environments. They contain a variety of metallic elements and are important solid mineral resources on the seabed. How best to quickly and accurately identify polymetallic nodules is one of the key questions of marine development and deep-sea-mineral-resource utilization. We propose a method that uses YOLOv5s as a reference network and integrates the IoU (Intersection over Union) and the Wasserstein distance in the optimal transmission theory to accurately identify different sizes of polymetallic nodules. Experiment using deep-sea hyperspectral data obtained from the Peru Basin was performed. The results showed that better recognition effects were achieved when the fusion ratio of overlap and Wasserstein distance metric was 0.5, and the accuracy of the proposed algorithm reached 84.5%, which was 6.2% higher than that of the original baseline network. In addition, the rest of the performance indexes were also improved significantly compared to traditional methods.

Diurnal to Decadal Variability in Land Surface and Air Temperature Gradient from 2002 to 2022 over the Contiguous United States

Abstract The surface and air temperature gradient (TS00 − Tair) drives the development of the convective boundary layer and the occurrence of clouds and precipitation. However, its variability is still poorly understood due to the lack of high-quality observations. This study fills in this gap by investigating the diurnal to decadal variability in TS00 − Tair from 2002 to 2022 based on hourly observations collected at over 100 stations of the U.S. Climate Reference Network. It is found that TS00 − Tair reaches its maximum at noon with an average of 6.85°C over the contiguous United States, which decreases to 4.28°C when the soil moisture exceeds 30%. The daily minimum of TS00 − Tair has an average of −2.08°C, which generally occurs in the early evening but is postponed as the cloud fraction decreases. Moreover, while existing studies have used the near-surface soil temperature, such as the 5-cm soil temperature (TS05), to calculate TS05 − Tair, we find that TS00 − Tair and TS05 − Tair have opposite diurnal cycles, and their amplitudes differed drastically. The daily minimum of TS00 − Tair has a significant decreasing trend (−0.50° ± 0.007°C decade−1) from 2002 to 2022 due to Tair increasing at a higher rate than TS00 during the nighttime. The occurrence frequency of near-surface stable conditions (TS00 − Tair < 0) increases significantly, and the frequency of unstable conditions (TS00 − Tair > 0) decreases notably throughout the year except for winter. When it is stable, the magnitude of TS00 − Tair tends to decrease while the TS00 − Tair tends to increase when it is unstable, which is consistent with the drying condition caused by the precipitation deficit. This study provides the first observational evidence on how TS00 − Tair responds to warming. Significance Statement The impact of global warming on surface-air temperature gradients is a crucial scientific issue that needs to be addressed. These gradients determine changes in cloud and precipitation, affecting water resources. However, traditional surface temperature measurements from weather stations are of high uncertainty due to direct exposure to the insolation. Satellite retrieval of surface temperature is limited by the availability of clear sky conditions, with low accuracy for temperature gradient calculations. Despite their importance, high-accuracy data of land surface temperature are still lacking. To address this issue, the U.S. Climate Reference Network (USCRN) uses infrared radiometers to continuously monitor surface temperature with high accuracy and sampling frequency. This study reports on surface-air temperature gradients at more than 100 U.S. stations, providing insight into diurnal to decadal variability over the contiguous United States. The study also highlights the significant difference between the land surface temperature–air temperature gradient and soil temperature–air temperature gradient.

Inventory of current practices regarding hematopoietic stem cell transplantation in metachromatic leukodystrophy in Europe and neighboring countries

BackgroundFor decades, early allogeneic stem cell transplantation (HSCT) has been used to slow neurological decline in metachromatic leukodystrophy (MLD). There is lack of consensus regarding who may benefit, and guidelines are lacking. Clinical practice relies on limited literature and expert opinions. The European Reference Network for Rare Neurological Diseases (ERN-RND) and the MLD initiative facilitate expert panels for treatment advice, but some countries are underrepresented. This study explores organizational and clinical HSCT practices for MLD in Europe and neighboring countries to enhance optimization and harmonization of cross-border MLD care.MethodsA web-based EUSurvey was distributed through the ERN-RND and the European Society for Blood and Marrow Transplantation Inborn Errors Working Party. Personal invitations were sent to 89 physicians (43 countries) with neurological/metabolic/hematological expertise. The results were analyzed and visualized using Microsoft Excel and IBM SPSS statistics.ResultsOf the 30 countries represented by 42 respondents, 23 countries offer HSCT for MLD. The treatment is usually available in 1–3 centers per country (18/23, 78%). Most countries have no or very few MLD patients transplanted during the past 1–5 years. The eligibility criteria regarding MLD subtype, motor function, IQ, and MRI largely differ across countries.ConclusionHSCT for MLD is available in most European countries, but uncertainties exist in Eastern and South-Eastern Europe. Applied eligibility criteria and management vary and may not align with the latest scientific insights, indicating physicians’ struggle in providing evidence-based care. Interaction between local physicians and international experts is crucial for adequate treatment decision-making and cross-border care in the rapidly changing MLD field.

Benchmarks for Pediatric Surgical Registries: Recommendations for the Assessment and Grading of Complications.

Procedure-related registries in general surgical practice offer a platform for prospective trials, the pooling of data, and detailed outcome analysis. Recommendations by the Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) collaboration and Outcome4Medicine have further improved the uniform reporting of complications and adverse events.In the pediatric surgical network, disease-specific registries for rare and inherited congenital anomalies are gaining importance, fostering international collaborations on studies of low-incidence diseases. However, to date, reporting of complications in the pediatric surgical registries has been inconsistent. Therefore, the European Reference Network for Rare Inherited and Congenital Anomalies (ERNICA) recently endorsed the validation of the first severity grading system for children. The planned reform of the European Paediatric Surgical Audit (EPSA) registry, which includes the implementation of the Clavien-Madadi classification, represents a further effort to establish uniform outcome reporting.This article provides an overview of experiences with surgical registries and complication reporting, along with the potential application of this knowledge to future pediatric surgical practice.

Internal dynamics of patent reference networks using the Bray–Curtis dissimilarity measure

BackgroundPatents are indicators of technological developments. The science & technology categories, to which they are assigned to, form a directed, weighted network where the links are the references between patents belonging to the respective categories. This network can be conceived as a kind of intellectual ecology, lending itself to mathematical analyses analogous to those carried out in numerical ecology. The non-metric Bray–Curtis dissimilarity, commonly used in quantitative ecology, can be used to describe the internal dynamics of this network.ResultsWhile the degree-distribution of the network remained stable during the studied years, that of the sub-networks of with at least k links showed that k = 5 is a critical number of citations: this many are needed that the bias towards already highly cited works come into effect (preferential attachment). Using the dij Bay-Curtis dissimilarity between nodes i and j, a surprising pattern emerged: the log-probability of a change in dij during a quarter of year depended linearly, with a negative coefficient, on the magnitude of the change itself.ConclusionsThe developed methodology could be useful to detect emerging technological developments, to aid decisions, for example, on resource allocation. The pattern found on the internal dynamics of the system depends on the categorisation of the patents, therefore it can serve as an indicator when comparing different categorisation methods.Graphical