Global Aviation Monitor (GAM) - December 2017

Objective The development, delivery and evaluation of a training programme for medical and nursing professionals on best practice for informing families of their child’s disability. Design A 2 h training course on ‘Best practice guidelines for informing families of their child’s disability’ was designed based on the findings of a nationally representative study of parents and professionals. The classroom-based course comprised a presentation of the research and recommendations of the best practice guidelines; a DVD film of parent stories and professional advice; group discussion; and a half-hour input from a parent of two children with disabilities. An anonymous, pretraining and post-training questionnaire was administered to measure knowledge and confidence levels, using scales adapted from a study by Ferguson et al (2006). Participants 235 participants, including medical students, nursing students, and junior hospital doctors (JHDs). Outcome measures Knowledge of best practice and confidence in communicating diagnosis of disability. Results Significant improvements in knowledge (time 1 mean (M)=14.31, SD=2.961; time 2 M=18.17, SD=3.068) and confidence (time 1 M=20.87, SD=5.333; time 2 M=12.43, SD=3.803) following training were found. In addition, a significant interaction between time and cohort (medical students, nurses and JHDs) was found for knowledge. Further examination suggested medical students’ knowledge was developing to the extent that post-training, their scores were higher than nurses, but not significantly different to JHDs. Conclusions The increase in reported levels of knowledge and confidence following training in best practice for informing families of their child’s disability indicates the potential for providing communication skills training in this area.Participation of EM Bettendorf in this project was funded by the Mental Health/Developmental Disabilities Grant (NIMH/NIH R25 MH071286) at Children’s Hospital Boston (Dr K Munir, PI). Funding for the wider pilot project of which the current study forms a part, was provided by the Health Services National Partnership Forum and the National Federation of Voluntary Bodies Providing Services to People with Intellectual Disabilities.peer-reviewe

Exploring the functionalisation of the thieno[2,3-d]pyrimidinedione core: late stage access to highly substituted 5-carboxamide-6-aryl scaffolds

The thieno[2,3-d]pyrimidinedione core is found as a component in a range of pharmaceutically active compounds, however, synthetic approaches to these scaffolds rely on access to functionalised, highly substituted thiophenes. Here we describe a new approach for the preparation of 5-carboxamide-6-aryl analogues that involves a two-step synthesis of the thieno[2,3-d]pyrimidinedione core from a readily available mercaptouracil derivative. Thio-alkylation with ethyl 3-bromopyruvate, followed by cyclisation and dehydration mediated by polyphosphoric acid allowed the scalable synthesis of the thieno[2,3-d] pyrimidinedione unit. The late-stage functionalisation of this core motif via bromination of the thiophene ring and a subsequent Suzuki-Miyaura reaction as the key steps permitted access to a novel library of 5-carboxamide-6-aryl analogues. The physicochemical properties of these compounds were determined, generating an insight into the potential bioavailability of these scaffolds. Based on these results, a selection of the novel 5-carboxamide-6-aryl analogues were tested as lactate uptake inhibitors of monocarboxylate transporters 1, 2 and 4 in Xenopus oocytes

Yield-biodiversity trade-off in patchy fields of Miscanthus × giganteus

Increasing crop productivity to meet rising demands for food and energy, but doing so in an environmentally sustainable manner, is one of the greatest challenges for agriculture to date. In Ireland, Miscanthus 9 giganteus has the potential to become a major feedstock for bioenergy production, but the economic feasibility of its cultivation depends on high yields. Miscanthus fields can have a large number of gaps in crop cover, adversely impacting yield and hence economic viability. Predominantly positive effects of Miscanthus on biodiversity reported from previous research might be attributable to high crop patchiness, particularly during the establishment phase. The aim of this research was to assess crop patchiness on a field scale and to analyse the relationship between Miscanthus yield and species richness and abundance of selected taxa of farmland wildlife. For 14 Miscanthus fields at the end of their establishment phase (4–5 years after planting), which had been planted either on improved grassland (MG) or tilled arable land (MT), we determined patchiness of the crop cover, percentage light penetration (LP) to the lower canopy, Miscanthus shoot density and height, vascular plants and epigeic arthropods. Plant species richness and noncrop vegetation cover in Miscanthus fields increased with increasing patchiness, due to higher levels of LP to the lower canopy. The species richness of ground beetles and the activity density of spiders followed the increase in vegetation cover. Plant species richness and activity density of spiders on both MT and MG fields, as well as vegetation cover and activity density of ground beetles on MG fields, were negatively associated with Miscanthus yield. In conclusion, positive effects of Miscanthus on biodiversity can diminish with increasing productivity. This matter needs to be considered when assessing the relative ecological impacts of developing biomass crops in comparison with other land use. Keywords: Araneae, Carabidae, crop cover, light penetration, Miscanthus establishment, patchiness, vascular plants, vegetation coverYield-biodiversity trade-off in patchy fields of Miscanthus × giganteuspublishedVersio

A Survey of New Temperature-Sensitive, Embryonic-Lethal Mutations in C. elegans: 24 Alleles of Thirteen Genes

To study essential maternal gene requirements in the early C. elegans embryo, we have screened for temperature-sensitive, embryonic lethal mutations in an effort to bypass essential zygotic requirements for such genes during larval and adult germline development. With conditional alleles, multiple essential requirements can be examined by shifting at different times from the permissive temperature of 15°C to the restrictive temperature of 26°C. Here we describe 24 conditional mutations that affect 13 different loci and report the identity of the gene mutations responsible for the conditional lethality in 22 of the mutants. All but four are mis-sense mutations, with two mutations affecting splice sites, another creating an in-frame deletion, and one creating a premature stop codon. Almost all of the mis-sense mutations affect residues conserved in orthologs, and thus may be useful for engineering conditional mutations in other organisms. We find that 62% of the mutants display additional phenotypes when shifted to the restrictive temperature as L1 larvae, in addition to causing embryonic lethality after L4 upshifts. Remarkably, we also found that 13 out of the 24 mutations appear to be fast-acting, making them particularly useful for careful dissection of multiple essential requirements. Our findings highlight the value of C. elegans for identifying useful temperature-sensitive mutations in essential genes, and provide new insights into the requirements for some of the affected loci

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p

Characterization of the Metabolic Phenotype of Rapamycin-Treated CD8+ T Cells with Augmented Ability to Generate Long-Lasting Memory Cells

Cellular metabolism plays a critical role in regulating T cell responses and the development of memory T cells with long-term protections. However, the metabolic phenotype of antigen-activated T cells that are responsible for the generation of long-lived memory cells has not been characterized.. than untreated control T cells. In contrast to that control T cells only increased glycolysis, rapamycin-treated T cells upregulated both glycolysis and oxidative phosphorylation (OXPHOS). These rapamycin-treated T cells had greater ability than control T cells to survive withdrawal of either glucose or growth factors. Inhibition of OXPHOS by oligomycin significantly reduced the ability of rapamycin-treated T cells to survive growth factor withdrawal. This effect of OXPHOS inhibition was accompanied with mitochondrial hyperpolarization and elevation of reactive oxygen species that are known to be toxic to cells.Our findings indicate that these rapamycin-treated T cells may represent a unique cell model for identifying nutrients and signals critical to regulating metabolism in both effector and memory T cells, and for the development of new methods to improve the efficacy of adoptive T cell cancer therapy

Sectoral impacts on the diversity of carabid beetles (Coleoptera: Carabidae) and their associated ecosystem service of biocontrol

This thesis aimed to provide an understanding of how human-induced changes in the economic sectors of agriculture and transport affect carabid diversity, potential carabidmediated biocontrol and predator-pest interactions. The research involved both observational and manipulative laboratory and field-based studies. Observational research consisted of two large-scale investigations of (1) the impact of Miscanthus and oilseed rape production (n=45) and (2) the impact of horticultural and ecological based landscaping of roadside verges (n=64). This research is the first record of carabid diversity, potential biocontrol and community assemblage with respect to bioenergy crop production and roadside landscaping in an Irish context and it is also an important addition to the limited knowledge of carabid populations in these ecosystems internationally. Manipulative work involved the examination of the role predator identity, diversity and biomass play in the suppression of pollen beetle larvae (an economically damaging insect pest of oilseed rape in Europe), using a novel experimental design called ‘simplex’. To complement this research, an additional field study on the impact of low and high oilseed rape pesticide management on carabid species richness and abundance, and crop yield, was also conducted. This research is a great contribution to the existing understanding of what constitutes the important components of predator biodiversity and expands the knowledge of the usefulness of carabid predators in the context of pollen beetle larvae control. In particular, the work shows that the abundance or biomass of beetles has an effect that is far larger than the effect of diversity on the capacity of beetles to consume prey. In turn, the field study showed that pesticide applications had little impact on yield, or carabid richness, but that carabid abundance/biomass declined drastically. The work provides compelling evidence that management practices erode the useful components of biodiversity that are essential for the delivery of biocontrol services

Intonation and Language Contact: A Case Study of Two Varieties of Peruvian Spanish

300 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.This study offers an initial description of both Peruvian Spanish and Quechua intonation using instrumental analysis. Lima and some Cuzco Spanish speakers are shown to coincide with previous descriptions of other varieties of Spanish, depending on the feature considered. More variation is found within Cuzco, including patterns of tonic peak alignment, which are not previously found in broad focus, except in other contact varieties of Spanish. In addition, Cuzco Quechua coincides with the feature of aligning prenuclear peaks within the stressed syllable. This data then suggest the possibility of contact between prosodic systems. However, not all intonation features are shown to be influenced. For example, the final fall in questions in Quechua is maintained, while the final rise in questions in Spanish is produced by all three language groups in Cuzco. This research then demonstrates the importance of examining several intonation features for possible contact, since not all features may undergo the same change.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Intonation and Language Contact: A Case Study of Two Varieties of Peruvian Spanish

300 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.This study offers an initial description of both Peruvian Spanish and Quechua intonation using instrumental analysis. Lima and some Cuzco Spanish speakers are shown to coincide with previous descriptions of other varieties of Spanish, depending on the feature considered. More variation is found within Cuzco, including patterns of tonic peak alignment, which are not previously found in broad focus, except in other contact varieties of Spanish. In addition, Cuzco Quechua coincides with the feature of aligning prenuclear peaks within the stressed syllable. This data then suggest the possibility of contact between prosodic systems. However, not all intonation features are shown to be influenced. For example, the final fall in questions in Quechua is maintained, while the final rise in questions in Spanish is produced by all three language groups in Cuzco. This research then demonstrates the importance of examining several intonation features for possible contact, since not all features may undergo the same change.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

The Handbook of Hispanic Linguistics

Reflecting the growth and increasing global importance of the Spanish language, The Handbook of Hispanic Linguistics brings together a team of renowned Spanish linguistics scholars to explore both applied and theoretical work in this field. Features 41 newly-written essays contributed by leading language scholars that shed new light on the growth and significance of the Spanish language Combines current applied and theoretical research results in the field of Spanish linguistics Explores all facets relating to the origins, evolution, and geographical variations of the Spanish language Examines topics including second language learning, Spanish in the classroom, immigration, heritage languages, and bilingualism.The Handbook of Hispanic Linguistics -- Contents -- List of Figures -- List of Tables -- Notes on Contributors -- Editors' Note -- 1 Geographical and Social Varieties of Spanish: An Overview -- 2 The Spanish-based Creoles -- 3 Spanish Among the Ibero-Romance Languages -- 4 Spanish in Contact with Amerindian Languages -- 5 The Phonemes of Spanish -- 6 Main Phonological Processes -- 7 Syllable Structure -- 8 Stress and Rhythm -- 9 Intonation in Spanish -- 10 Morphophonological Alternations -- 11 Derivation and Compounding -- 12 Morphological Structure of Verbal Forms -- 13 Forms of Address -- 14 Structure of the Noun Phrase -- 15 Indefiniteness and Specificity -- 16 Quantification -- 17 Structure of the Verb Phrase -- 18 Tense and Aspect -- 19 Mood: Indicative vs. Subjunctive -- 20 The Simple Sentence -- 21 Clitics in Spanish -- 22 Ser and Estar: The Individual/Stage-level Distinction and Aspectual Predication -- 23 Passives and se Constructions -- 24 Coordination and Subordination -- 25 Wh-movement: Interrogatives, Exclamatives, and Relatives -- 26 Binding: Deixis, Anaphors, Pronominals -- 27 Empty Categories and Ellipsis -- 28 Word Order and Information Structure -- 29 Speech Acts -- 30 Discourse Syntax -- 31 Historical Morphosyntax and Grammaticalization -- 32 First Language Acquisition of Spanish Sounds and Prosody -- 33 Spanish as a Second Language and Teaching Methodologies -- 34 The L2 Acquisition of Spanish Phonetics and Phonology -- 35 Theoretical Perspectives on the L2 Acquisition of Spanish -- 36 Spanish as a Heritage Language -- 37 Acquisition of Spanish in Bilingual Contexts -- 38 Reading Words and Sentences in Spanish -- 39 Language Impairments -- 40 Lexical Access in Spanish as a First and Second Language -- IndexReflecting the growth and increasing global importance of the Spanish language, The Handbook of Hispanic Linguistics brings together a team of renowned Spanish linguistics scholars to explore both applied and theoretical work in this field. Features 41 newly-written essays contributed by leading language scholars that shed new light on the growth and significance of the Spanish language Combines current applied and theoretical research results in the field of Spanish linguistics Explores all facets relating to the origins, evolution, and geographical variations of the Spanish language Examines topics including second language learning, Spanish in the classroom, immigration, heritage languages, and bilingualism.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries