Thermal degradation of Cross-Linked Polyisoprene and Polychloroprene

Polyisoprene and polychloroprene have been cross-linked either in solution or in solid state using free radical initiators. In the comparable experimental conditions higher cross-linking density was observed in the solid state process. Independent of the cross-linking method, polychloroprene tended to give a higher gel content and cross-link density than does polyisoprene. Infrared characterization of the cross-linked materials showed cis-trans isomerization occurred in the polyisoprene initiated by benzoyl peroxide, whereas no isomerization was found in the samples initiated by dicumyl peroxide. Polyisoprene does not cross-link by heating in a thermal analyzer, whereas polychloroprene easily undergoes cross-linking in such conditions. Infrared spectroscopy showed that in the case of polyisoprene, rearrangements occur upon heating which lead to the formation of terminal double bonds, while polychloroprene loses hydrogen chlorine which leads to a conjugated structure. There is apparently some enhancement of the thermal and thermal oxidative stability of polyisoprene because of the cross-linking. Cross-linked polychloroprene is less thermally stable than the virgin polymer. Cross-linking promotes polymers charring in the main step of weight loss in air, which leads to enhanced transitory char

Cognitive behaviour therapy plus aerobic exercise training to increase activity in patients with myotonic dystrophy type 1 (DM1) compared to usual care (OPTIMISTIC):Study protocol for randomised controlled trial

Peer reviewedPublisher PD

A conceptual framework of the adoption and practice of environmental actions in households

Securing public participation in environmental actions such as recycling, energy conservation measures and green consumerism is a means of progressing towards sustainable consumption. Participation in environmental actions (EAs) has typically been studied from the individual perspective, thus largely ignoring the social context of the household which may undermine effective behaviour change and green marketing strategies. This paper advances understanding of the adoption and practice of EAs from the household perspective by drawing together the limited and fragmented work which has examined EA participation from the household perspective, and integrating it with two relevant literatures – the household decision making literature and the literature which has examined EA participation from the individual perspective. The literatures are drawn together into a framework covering household member involvement in EA adoption and practice, the decision making process leading to EA adoption, decision making strategies and communication within the household, the maintenance of repetitive EAs, the factors influencing household member involvement including activity types and situational, household and individual characteristics, and how the individual characteristic of relative interest is shaped. We make a theoretical contribution by presenting a holistic understanding of the adoption and practice of EAs in households, which was previously lacking from the EA participation literature. By highlighting the elements of the conceptual framework that require further investigation, the authors also set out an agenda for research into EA participation from the household perspective

The Human Phenotype Ontology project:linking molecular biology and disease through phenotype data

The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online

Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome

Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a “second hit,” that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome

Ecological impacts of non-native Pacific oysters (Crassostrea gigas) and management measures for protected areas in Europe

Pacific oysters are now one of the most ‘globalised’ marine invertebrates. They dominate bivalve aquaculture production in many regions and wild populations are increasingly becoming established, with potential to displace native species and modify habitats and ecosystems. While some fishing communities may benefit from wild populations, there is now a tension between the continued production of Pacific oysters and risk to biodiversity, which is of particular concern within protected sites. The issue of the Pacific oyster therefore locates at the intersection between two policy areas: one concerning the conservation of protected habitats, the other relating to livelihoods and the socio-economics of coastal aquaculture and fishing communities. To help provide an informed basis for management decisions, we first summarise evidence for ecological impacts of wild Pacific oysters in representative coastal habitats. At local scales, it is clear that establishment of Pacific oysters can significantly alter diversity, community structure and ecosystem processes, with effects varying among habitats and locations and with the density of oysters. Less evidence is available to evaluate regional-scale impacts. A range of management measures have been applied to mitigate negative impacts of wild Pacific oysters and we develop recommendations which are consistent with the scientific evidence and believe compatible with multiple interests. We conclude that all stakeholders must engage in regional decision making to help minimise negative environmental impacts, and promote sustainable industry development

Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome.METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants.RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving.CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.</p

Immunohistochemistry on a Panel of Emery-Dreifuss Muscular Dystrophy Samples Reveals Nuclear Envelope Proteins as Inconsistent Markers for Pathology

Reports of aberrant distribution for some nuclear envelope proteins in cells expressing a few Emery–Dreifuss muscular dystrophy mutations raised the possibility that such protein redistribution could underlie pathology and/or be diagnostic. However, this disorder is linked to 8 different genes encoding nuclear envelope proteins, raising the question of whether a particular protein is most relevant. Therefore, myoblast/fibroblast cultures from biopsy and tissue sections from a panel of nine Emery–Dreifuss muscular dystrophy patients (4 male, 5 female) including those carrying emerin and FHL1 (X-linked) and several lamin A (autosomal dominant) mutations were stained for the proteins linked to the disorder. As tissue-specific nuclear envelope proteins have been postulated to mediate the tissue-specific pathologies of different nuclear envelopathies, patient samples were also stained for several muscle-specific nuclear membrane proteins. Although linked proteins nesprin 1 and SUN2 and muscle-specific proteins NET5/Samp1 and Tmem214 yielded aberrant distributions in individual patient cells, none exhibited defects through the larger patient panel. Muscle-specific Tmem38A normally appeared in both the nuclear envelope and sarcoplasmic reticulum, but most patient samples exhibited a moderate redistribution favouring the sarcoplasmic reticulum. The absence of striking uniform defects in nuclear envelope protein distribution indicates that such staining will be unavailing for general diagnostics, though it remains possible that specific mutations exhibiting protein distribution defects might reflect a particular clinical variant. These findings further argue that multiple pathways can lead to the generally similar pathologies of this disorder while at the same time the different cellular phenotypes observed possibly may help explain the considerable clinical variation of EDMD

Abstracts from the NIHR INVOLVE Conference 2017

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