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Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis and frontotemporal dementia, based on identification of likely pathogenic variants in patients from distinct amyotrophic lateral sclerosis and frontotemporal dementia cohorts. By screening a multicentric French cohort of 448 unrelated probands presenting with cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent from public databases and predicted pathogenic by multiple in silico tools. In addition, gene burden analyses in the 100 000 Genomes project (100KGP) showed enrichment of TUBA4A rare variants in the inherited ataxia group compared to controls [odds ratio: 57.0847 (10.2-576.7); P = 4.02 ×10-7]. Taken together, we report 12 patients presenting with spasticity and/or cerebellar ataxia and harbouring a predicted pathogenic TUBA4A missense mutation, including five confirmed de novo cases and a mutation previously reported in a large family presenting with spastic ataxia. Cultured fibroblasts from three patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organization and dynamics, providing insight of TUBA4A variants pathogenicity. Our data confirm the identification of a hereditary spastic ataxia disease gene with variable age of onset, expanding the clinical spectrum of TUBA4A associated phenotypes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The hyperdiverse wood-inhabiting fungi play a crucial role in the global carbon cycle, but often are threatened by deadwood removal, particularly in temperate forests dominated by European beech ( Fagus sylvatica ) and Oriental beech ( Fagus orientalis ). To study the impact of abiotic drivers, deadwood factors, forest management and biogeographical patterns in forests of both beech species on fungal composition and diversity, we collected 215 deadwood-drilling samples in 18 forests from France to Armenia and identified fungi by meta-barcoding. In our analyses, we distinguished the patterns driven by rare, common, and dominant species using Hill numbers. Despite a broad overlap in species, the fungal composition with focus on rare species was determined by Fagus species, deadwood type, deadwood diameter, precipitation, temperature, and management status in decreasing order. Shifting the focus on common and dominant species, only Fagus species, both climate variables and deadwood type remained. The richness of species within the deadwood objects increased significantly only with decay stage. Gamma diversity in European beech forests was higher than in Oriental beech forests. We revealed the highest gamma diversity for old-growth forests of European beech when focusing on dominant species. Our results implicate that deadwood retention efforts, focusing on dominant fungi species, critical for the decay process, should be distributed across precipitation and temperature gradients and both Fagus species. Strategies focusing on rare species should additionally focus on different diameters and on the conservation of old-growth forests., Competing Interests: The authors have no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Broad-scale monitoring of arthropods is often carried out with passive traps ( e.g., Malaise traps) that can collect thousands of specimens per sample. The identification of individual specimens requires time and taxonomic expertise, limiting the geographical and temporal scale of research and monitoring studies. DNA metabarcoding of bulk-sample homogenates has been found to be faster, efficient and reliable, but the destruction of samples prevents a posteriori validation of species occurrences and relative abundances. Non-destructive metabarcoding of DNA extracted from collection medium has been applied in a limited number of studies, but further tests of efficiency are required with different trap types and collection media to assess the consistency of the method., Methods: We quantified the detection rate of arthropod species when applying non-destructive DNA metabarcoding with a short (127-bp) fragment of mitochondrial COI on two combinations of passive traps and collection media: (1) water with monopropylene glycol (H 2 O-MPG) used in window-flight traps (WFT, 53 in total); (2) ethanol with monopropylene glycol (EtOH-MPG) used in Malaise traps (MT, 27 in total). We then compared our results with those obtained for the same samples using morphological identification (for WFTs) or destructive metabarcoding of bulk homogenate (for MTs). This comparison was applied as part of a larger study of arthropod species richness in silver fir ( Abies alba Mill., 1759) stands across a range of climate-induced tree dieback levels and forest management strategies., Results: Of the 53 H 2 O-MPG samples from WFTs, 16 produced no metabarcoding results, while the remaining 37 samples yielded 77 arthropod MOTUs in total, of which none matched any of the 343 beetle species morphologically identified from the same traps. Metabarcoding of 26 EtOH-MPG samples from MTs detected more arthropod MOTUs (233) than destructive metabarcoding of homogenate (146 MOTUs, 8 orders), of which 71 were shared MOTUs, though MOTU richness per trap was similar between treatments. While we acknowledge the failure of metabarcoding from WFT-derived collection medium (H 2 O-MPG), the treatment of EtOH-based Malaise trapping medium remains promising. We conclude however that DNA metabarcoding from collection medium still requires further methodological developments and cannot replace homogenate metabarcoding as an approach for arthropod monitoring. It can be used nonetheless as a complementary treatment when enhancing the detection of soft-bodied arthropods like spiders and Diptera., Competing Interests: The authors declare there are no competing interests., (©2023 Sire et al.)

Agriculture and forestry cover more than 75% of Europe, and invertebrate pests are a costly challenge for these two economic sectors. Landscape management is increasingly promoted as a solution to enhance biological pest control, but little is known on its effects on adjacent crop fields and woodlands. This study aims to explore the effect of the proportion of woodlands and permanent grasslands as well as crop diversity on biological pest control simultaneously in cereals fields and woodland patches, in south-western France. We used different types of sentinel prey as well as bird and carabid community metrics to assess biological pest control potential in these two ecosystems. We first show that land cover variables influence biological pest control both in cereal fields and woodland patches, but have antagonistic effects in the two ecosystems. Although results vary according to the biological control indicator considered, we show that increasing landscape heterogeneity represents a valuable solution to manage trade-offs and promote higher average predation rates across forests and cereal fields. Our study therefore calls for more integrative studies to identify landscape management strategies that enable nature-based solutions across ecosystems., (© 2023. Springer Nature Limited.)

Protecting structural features, such as tree-related microhabitats (TreMs), is a cost-effective tool crucial for biodiversity conservation applicable to large forested landscapes. Although the development of TreMs is influenced by tree diameter, species, and vitality, the relationships between tree age and TreM profile remain poorly understood. Using a tree-ring-based approach and a large data set of 8038 trees, we modeled the effects of tree age, diameter, and site characteristics on TreM richness and occurrence across some of the most intact primary temperate forests in Europe, including mixed beech and spruce forests. We observed an overall increase in TreM richness on old and large trees in both forest types. The occurrence of specific TreM groups was variably related to tree age and diameter, but some TreM groups (e.g., epiphytes) had a stronger positive relationship with tree species and elevation. Although many TreM groups were positively associated with tree age and diameter, only two TreM groups in spruce stands reacted exclusively to tree age (insect galleries and exposed sapwood) without responding to diameter. Thus, the retention of trees for conservation purposes based on tree diameter appears to be a generally feasible approach with a rather low risk of underrepresentation of TreMs. Because greater tree age and diameter positively affected TreM development, placing a greater emphasis on conserving large trees and allowing them to reach older ages, for example, through the establishment of conservation reserves, would better maintain the continuity of TreM resource and associated biodiversity. However, this approach may be difficult due to the widespread intensification of forest management and global climate change., (© 2023 Society for Conservation Biology.)

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited late-onset neurological disease caused by bi-allelic AAGGG pentanucleotide expansions within intron 2 of RFC1. Despite extensive studies, the pathophysiological mechanism of these intronic expansions remains elusive. We screened by clinical exome sequencing two unrelated patients presenting with late-onset ataxia. A repeat-primer polymerase chain reaction was used for RFC1 AAGGG intronic expansion identification. RFC1 mRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction. We identified the first two CANVAS affected patients who are compound heterozygous for RFC1 truncating variants (p.Arg388* and c.575delA, respectively) and a pathological AAGGG expansion. RFC1 expression studies in whole blood showed a significant reduction of RFC1 mRNA for both patients compared to three patients with bi-allelic RFC1 expansions. In conclusion, this observation provides clues that suggest bi-allelic RFC1 conditional loss-of-function as the cause of the disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tree to tree interactions are important structuring mechanisms for forest community dynamics. Forest management takes advantage of competition effects on tree growth by removing or retaining trees to achieve management goals. Both competition and silviculture have, thus, a strong effect on density and distribution of tree related microhabitats which are key features for forest taxa at the stand scale. In particular, spatially-explicit data to understand patterns and mechanisms of tree-related microhabitats formation in forest stands are rare. To train and eventually improve decision-making capacities related to the integration of biodiversity aspects into forest management plot of one hectare, so called marteloscopes were established in the frame of the 'European Integrate Network'. In each plot, a set of data is collected at the individual tree level and stored in a database, the 'I+ repository'. The 'I+ repository' is a centralised online database which serves for maintaining the data of all marteloscope plots. A subset of this repository was made publicly available via the Global Biodiversity Information Facility, based on a data-sharing policy. Data included are tree location in plot, tree species, forest mensuration data (diameter at breast height [cm], tree height [m]), tree status (living or standing dead) and tree-related microhabitats. Further, a visual assessment of timber quality classes is performed in order to provide an estimate of the economic value (market price) for each tree. This information is not part of the GBIF dataset., New Information: Currently 42,078 individual tree observations from 111 plots are made available via the Global Biodiversity Information Facility (GBIF). As the network of plots continues to expand, so does the database of tree-related microhabitats. Therefore, the database will undergo a regular update. The current version has a temporal coverage from March 2014 to December 2020. The innovation of this unique dataset is that it is based on a commonly agreed catalogue of tree microhabitats as a field reference list when assessing assessment protocol. The reference list is available in 17 languages and, thus, helps to guarantee compatibility of tree-related microhabitat assessments across countries and plots., (Sergey Zudin, Wilfried Heintz, Daniel Kraus, Frank Krumm, Laurent Larrieu, Andreas Schuck.)

In Europe, forest management has controlled forest dynamics to sustain commodity production over multiple centuries. Yet over-regulation for growth and yield diminishes resilience to environmental stress as well as threatens biodiversity, leading to increasing forest susceptibility to an array of disturbances. These trends have stimulated interest in alternative management systems, including natural dynamics silviculture (NDS). NDS aims to emulate natural disturbance dynamics at stand and landscape scales through silvicultural manipulations of forest structure and landscape patterns. We adapted a "Comparability Index" (CI) to assess convergence/divergence between natural disturbances and forest management effects. We extended the original CI concept based on disturbance size and frequency by adding the residual structure of canopy trees after a disturbance as a third dimension. We populated the model by compiling data on natural disturbance dynamics and management from 13 countries in Europe, covering four major forest types (i.e., spruce, beech, oak, and pine-dominated forests). We found that natural disturbances are highly variable in size, frequency, and residual structure, but European forest management fails to encompass this complexity. Silviculture in Europe is skewed toward even-aged systems, used predominately (72.9% of management) across the countries assessed. The residual structure proved crucial in the comparison of natural disturbances and silvicultural systems. CI indicated the highest congruence between uneven-aged silvicultural systems and key natural disturbance attributes. Even so, uneven-aged practices emulated only a portion of the complexity associated with natural disturbance effects. The remaining silvicultural systems perform poorly in terms of retention compared to tree survivorship after natural disturbances. We suggest that NDS can enrich Europe's portfolio of management systems, for example where wood production is not the primary objective. NDS is especially relevant to forests managed for habitat quality, risk reduction, and a variety of ecosystem services. We suggest a holistic approach integrating NDS with more conventional practices., (© 2022 The Ecological Society of America.)

Species richness, abundance and biomass of insects have recently undergone marked declines in Europe. We metabarcoded 211 Malaise-trap samples to investigate whether drought-induced forest dieback and subsequent salvage logging had an impact on ca. 3000 species of flying insects in silver fir Pyrenean forests. While forest dieback had no measurable impact on species richness, there were significant changes in community composition that were consistent with those observed during natural forest succession. Importantly, most observed changes were driven by rare species. Variation was explained primarily by canopy openness at the local scale, and the tree-related microhabitat diversity and deadwood amount at landscape scales. The levels of salvage logging in our study did not explain compositional changes. We conclude that forest dieback drives changes in species assemblages that mimic natural forest succession, and markedly increases the risk of catastrophic loss of rare species through homogenization of environmental conditions., (© 2022. The Author(s).)

Purpose: Diagnosis of inherited ataxia and related diseases represents a real challenge given the tremendous heterogeneity and clinical overlap of the various causes. We evaluated the efficacy of molecular diagnosis of these diseases by sequencing a large cohort of undiagnosed families., Methods: We analyzed 366 unrelated consecutive patients with undiagnosed ataxia or related disorders by clinical exome-capture sequencing. In silico analysis was performed with an in-house pipeline that combines variant ranking and copy-number variant (CNV) searches. Variants were interpreted according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines., Results: We established the molecular diagnosis in 46% of the cases. We identified 35 mildly affected patients with causative variants in genes that are classically associated with severe presentations. These cases were explained by the occurrence of hypomorphic variants, but also rarely suspected mechanisms such as C-terminal truncations and translation reinitiation., Conclusion: A significant fraction of the clinical heterogeneity and phenotypic overlap is explained by hypomorphic variants that are difficult to identify and not readily predicted. The hypomorphic C-terminal truncation and translation reinitiation mechanisms that we identified may only apply to few genes, as it relies on specific domain organization and alterations. We identified PEX10 and FASTKD2 as candidates for translation reinitiation accounting for mild disease presentation., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Objective: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited multisystem ataxia compromising cerebellar, vestibular, and sensory nerves, which has been associated to a pathogenic AAGGG(n) biallelic expansion repeat in the RFC1 gene. Our objective was to assess its prevalence in a French cohort of patients with idiopathic sporadic late-onset ataxia (ILOA), idiopathic early-onset ataxia (IEOA), or Multiple System Atrophy of Cerebellar type (MSA-C)., Methods: 163 patients were recruited in 3 French tertiary centers: 100 ILOA, 21 IEOA, and 42 patients with possible or probable MSA-C., Results: A pathogenic biallelic RFC1 AAGGG(n) repeat expansion was found in 15 patients: 15/100 in the ILOA group, but none in the IEOA and MSA-C subgroups. 14/15 patients had a CANVAS phenotype. Only 1/15 had isolated cerebellar ataxia, but also shorter biallelic expansions. Two RFC1 AAGGG(n) alleles were found in 78% of patients with a CANVAS phenotype. In one post-mortem case, the pathophysiological involvement of cerebellum and medullar posterior columns was found., Conclusion: Our study confirms the genetic heterogeneity of the CANVAS and that RFC1 repeat expansions should be searched for preferentially in case of unexplained ILOA associated with a sensory neuronopathy, but not particularly in patients classified as MSA-C., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Primary forests, defined here as forests where the signs of human impacts, if any, are strongly blurred due to decades without forest management, are scarce in Europe and continue to disappear. Despite these losses, we know little about where these forests occur. Here, we present a comprehensive geodatabase and map of Europe's known primary forests. Our geodatabase harmonizes 48 different, mostly field-based datasets of primary forests, and contains 18,411 individual patches (41.1 Mha) spread across 33 countries. When available, we provide information on each patch (name, location, naturalness, extent and dominant tree species) and the surrounding landscape (biogeographical regions, protection status, potential natural vegetation, current forest extent). Using Landsat satellite-image time series (1985-2018) we checked each patch for possible disturbance events since primary forests were identified, resulting in 94% of patches free of significant disturbances in the last 30 years. Although knowledge gaps remain, ours is the most comprehensive dataset on primary forests in Europe, and will be useful for ecological studies, and conservation planning to safeguard these unique forests., (© 2021. The Author(s).)

Background: Autophagy is the major intracellular degradation route in mammalian cells. Systemic ablation of core autophagy-related ( ATG ) genes in mice leads to embryonic or perinatal lethality, and conditional models show neurodegeneration. Impaired autophagy has been associated with a range of complex human diseases, yet congenital autophagy disorders are rare., Methods: We performed a genetic, clinical, and neuroimaging analysis involving five families. Mechanistic investigations were conducted with the use of patient-derived fibroblasts, skeletal muscle-biopsy specimens, mouse embryonic fibroblasts, and yeast., Results: We found deleterious, recessive variants in human ATG7 , a core autophagy-related gene encoding a protein that is indispensable to classical degradative autophagy. Twelve patients from five families with distinct ATG7 variants had complex neurodevelopmental disorders with brain, muscle, and endocrine involvement. Patients had abnormalities of the cerebellum and corpus callosum and various degrees of facial dysmorphism. These patients have survived with impaired autophagic flux arising from a diminishment or absence of ATG7 protein. Although autophagic sequestration was markedly reduced, evidence of basal autophagy was readily identified in fibroblasts and skeletal muscle with loss of ATG7. Complementation of different model systems by deleterious ATG7 variants resulted in poor or absent autophagic function as compared with the reintroduction of wild-type ATG7 ., Conclusions: We identified several patients with a neurodevelopmental disorder who have survived with a severe loss or complete absence of ATG7, an essential effector enzyme for autophagy without a known functional paralogue. (Funded by the Wellcome Centre for Mitochondrial Research and others.)., (Copyright © 2021 Massachusetts Medical Society.)

Despite the key importance of the landscape matrix for bats, we still not fully understand how the effect of forest composition interacts at combined stand and landscape scales to shape bat communities. In addition, we lack detailed knowledge on the effects of local habitat structure on bat-prey relationships in forested landscapes. We tested the assumptions that (i) forest composition has interacting effects on bats between stand and landscape scales; and (ii) stand structure mediates prey abundance effects on bat activity. Our results indicated that in conifer-dominated landscapes (> 80% of coniferous forests) bat activity was higher in stands with a higher proportion of deciduous trees while bats were less active in stands with a higher proportion of deciduous trees in mixed forest landscapes (~ 50% of deciduous forests). Moth abundance was selected in the best models for six among nine bat species. The positive effect of moth abundance on Barbastella barbastellus was mediated by vegetation clutter, with dense understory cover likely reducing prey accessibility. Altogether, our findings deepen our understanding of the ecological processes affecting bats in forest landscapes and strengthen the need to consider both landscape context and trophic linkage when assessing the effects of stand-scale compositional and structural attributes on bats.

Background: STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1 are now considered a frequent cause of cerebellar ataxia., Objective: We aimed to improve the clinical, radiological, and molecular delineation of SCAR16 and SCA48., Methods: Retrospective collection of patients with SCAR16 or SCA48 diagnosed in three French genetic centers (Montpellier, Strasbourg and Nancy)., Results: Here, we report four SCAR16 and nine SCA48 patients from two SCAR16 and five SCA48 unrelated French families. All presented with slowly progressive cerebellar ataxia. Additional findings included cognitive decline, dystonia, parkinsonism and swallowing difficulties. The age at onset was highly variable, ranging from 14 to 76 years. Brain MRI showed marked cerebellar atrophy in all patients. Phenotypic findings associated with STUB1 pathogenic variations cover a broad spectrum, ranging from isolated slowly progressive ataxia to severe encephalopathy, and include extrapyramidal features. We described five new pathogenic variations, two previously reported pathogenic variations, and two rare variants of unknown significance in association with STUB1-related disorders. We also report the first pathogenic variation associated with both dominant and recessive forms of inheritance (SCAR16 and SCA48)., Conclusion: Even though differences are observed between the recessive and dominant forms, it appears that a continuum exists between these two entities. While adding new symptoms associated with STUB1 pathogenic variations, we insist on the difficulty of genetic counselling in STUB1-related pathologies. Finally, we underscore the usefulness of DAT-scan as an additional clue for diagnosis.

ATP8A2-related disorders are autosomal recessive conditions that associate encephalopathy with or without hypotonia, psychomotor delay, abnormal movements, chorea, tremor, optic atrophy and cerebellar atrophy (CARMQ4). Through a multi-centric collaboration, we identified six point mutations (one splice site and five missense mutations) involving ATP8A2 in six individuals from five families. Two patients from one family with the homozygous p.Gly585Val mutation had a milder presentation without encephalopathy. Expression and functional studies of the missense mutations demonstrated that protein levels of four of the five missense variants were very low and lacked phosphatidylserine-activated ATPase activity. One variant p.Ile215Leu, however, expressed at normal levels and displayed phospholipid-activated ATPase activity similar to the non-mutated protein. We therefore expand for the first time the phenotype related to ATP8A2 mutations to less severe forms characterized by cerebellar ataxia without encephalopathy and suggest that ATP8A2 should be analyzed for all cases of syndromic or non-syndromic recessive or sporadic ataxia.

Next-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique. We applied a strategy of mini-exome coupled to read-depth based CNV analysis to a series of 33 patients with probable inherited ataxia and onset <50 years. The mini-exome consisted of the capture of 4,813 genes having associated clinical phenotypes. Pathogenic variants were found in 42% and variants of uncertain significance in 24% of the patients. These results are comparable to those from whole exome sequencing and better than previous targeted NGS studies. CNV and dynamic expansions of repeated CAG sequence were identified in three patients. We identified both atypical presentation of known ataxia genes (ATM, NPC1) and mutations in genes very rarely associated with ataxia (ERCC4, HSD17B4). We show that mini-exome bioinformatics data analysis allows the identification of CNV and dynamic expansions of repeated sequence. Our study confirms the diagnostic value of the proposed genetic analysis strategy. We also provide an algorithm for the multidisciplinary process of analysis, interpretation, and validation of NGS data., (© 2016 WILEY PERIODICALS, INC.)

Ataxia is a symptom that is often associated with syndromic inherited diseases. We previously reported the linkage of a novel syndrome, ataxia with blindness and deafness (SCAR3/SCABD, OMIM# 271250), to chromosome 6p21-p23 by linkage mapping of an Arab Israeli consanguineous family. We have now identified by whole-exome sequencing a homozygous missense mutation in the Arab Israeli family in the SLC52A2 gene located in 8qter, therefore excluding linkage of this family to 6p. We confirmed the involvement of SLC52A2 by the identification of a second mutation in an independent family with an identical syndromic presentation, which we suggest to name SCABD2. SCABD2 is therefore allelic to Brown-Vialleto-Van Laere syndrome type 2 defined by prominent motoneuronopathy and deafness, and also caused by SLC52A2 mutations. In the course of this project, we identified a clinically similar family with a homozygous missense mutation in PEX6, which is located in 6p21. Therefore, despite false linkage in the initial family, SCABD1/SCAR3 is located in 6p21 and is caused by PEX6 mutations. Both SLC52A2 and PEX6 should be included in screening panels for the diagnosis of syndromic inherited ataxias, particularly as patients with mutations in SLC52A2 can be ameliorated by riboflavin supplementation.

The detection of two frequent CFTR disease-causing variations in the context of a newborn screening program (NBS) usually leads to the diagnosis of cystic fibrosis (CF) and a relevant genetic counseling in the family. In the present study, CF-causing variants p.Phe508del (F508del) and c.3140-26A>G (3272-26A>G) were identified on a neonate with positive ImmunoReactive Trypsinogen test by the Elucigene™ CF30 kit. The CF diagnosis initially suggested, despite three inconclusive Sweat Chloride Tests (SCT), was finally ruled out after the familial segregation study combined with a negative SCT. Haplotype studies, based on the comparison of 80 p.Phe508del haplotypes, suggested a probable de novo occurrence of c.3140-26A>G on the p.Phe508del ancestral allele in this family. This false positive case emphasizes the importance of SCT in the NBS strategy. Moreover, it raises the need for familial segregation studies in CF and in overall molecular diagnosis strategy of autosomal recessive diseases., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)