Assessing sedation need and managing referred dentally anxious patients:is there a role for the Index of Sedation Need?

Aim: To conduct an exploratory investigation of public dental service (PDS) practitioners' planned sedation modality using a structural equation modelling approach, in order to identify the explanatory value of using the Index of Sedation Need (IOSN), or its component parts, to predict sedation modality in patients referred with dental anxiety. Methods: A convenience sample of patients referred to the PDS for dental anxiety management was invited to take part. The IOSN was completed for each patient (patient dental anxiety, medical and behavioural indicators and dental treatment complexity) as well as the American Society of Anesthesiologists Physical Status Classification System and the Case Mix Tool. The practitioners completed details of their planned sedation modality and identified normative dental treatment need. The data were entered onto an SPSS v21 database and subjected to frequency distributions, t-tests, correlation analysis and exploratory partial structural equation modelling (SEM). Results: Ninety-five percent of patients were ranked as MDAS 3 or 4, indicating high dental anxiety; 69% had a medical condition, which might impact on dental treatment and 82% had a dental treatment need, which was classified as intermediate/complex according to the IOSN. Eighty-eight percent of the patients in accordance with the IOSN required sedation: 62% of patients were assessed as requiring intravenous sedation. The IOSN discriminated between patients who were assessed as requiring more complex sedation modalities and had a greater normative treatment need. The SEM showed that the patient dental anxiety (P <0.02) and dental treatment complexity (P <0.02) predicted planned sedation modality. Functional morbidity was less strong, as a predictor, and was significant at the ten percent level. Conclusions: The IOSN is a useful and valid assessment of sedation need and predicted sedation modality for patients referred with high dental anxiety states and secondly, that component parts of the IOSN add explanatory value in practitioners' choice of planned sedation modality

A systematic review of physiological reactivity to stimuli in autism

Objective: The prevalence of abnormal behavioural responses to a variety of stimuli among individuals with autism has led researchers to examine whether physiological reactivity is typical in this population. The current paper reviewed studies assessing physiological reactivity to sensory, social and emotional, and stressor stimuli in individuals with autism. Methods: Systematic searches of electronic databases identified 57 studies that met our inclusion criteria. A novel measure of methodological quality suitable for use with non-randomised, non-interventional, psychophysiological studies was also developed and applied. Results: Individuals with autism were found to respond differently than typically developing controls in 78.6%, 66.7%, and 71.4% of sensory, social and emotional, and stressor stimulus classes, respectively. Conclusions: Individual differences in physiological reactivity are clearly present in autism, suggesting additional research is needed to determine the variables relating to physiological reactivity among those with ASD and to examine the possibility of physiological subtype responders in this population

Assembly-level analyses of accident-tolerant cladding concepts for a long-life civil marine SMR core using micro-heterogeneous duplex fuel

In this reactor physics study, we examine the neutronic performance of accident-tolerant fuel (ATF) claddings – austenitic type 310 stainless steel (310SS), ferritic Fe-20Cr-5Al (FeCrAl), advanced powder metallurgic ferritic (APMT), and silicon carbide (SiC)-based materials – as alternative cladding materials compared with Zircaloy-4 (Zr) cladding. The cores considered use 18% 235U enriched micro-heterogeneous ThO2-UO2 duplex fuel and, for purposes of comparison, 15% 235U enriched homogeneously mixed all-UO2 fuel, loaded into 13×13 pin arrays. A constant cladding coating thickness of 655 μm is assumed. We use the WIMS reactor physics code to analyse the associated reactivity, achievable discharge burnup, spectral variations, rim effect and reactivity feedback parameters for the candidate cladding materials at the assembly level. The results show that candidate fuels with 310SS cladding exhibit a ∼13% discharge burnup penalty compared to Zr due to the presence of a very high nickel (Ni) concentration. The high neutron absorption cross-sections of iron (Fe) in the FeCrAl and APMT claddings also lead to a ∼10% discharge burnup penalty. The fuels with SiC cladding can achieve a ∼1% higher discharge burnup compared to Zr due to the low thermal neutron absorption cross-sections of its constituents and the softer neutron spectrum. The claddings with lower capture cross-sections (SiC and Zr) exhibit higher relative fission power at the pellet periphery. For both candidate fuels, the end-of-life 239Pu (for UO2 fuel) and 233U (for duplex fuel) inventories are higher for the claddings (Fe-based: FeCrAl, APMT and steel-based: 310SS) with higher thermal capture cross-sections, unlike for SiC and Zr, where SiC provides higher end-of-life 239Pu and 233U inventories despite having lower capture cross-section than that of the Zr. Reactivity feedback parameter values (moderator and fuel temperature coefficients) are more negative for the duplex fuel than the UO2 fuel for all the candidate claddings, with claddings with harder spectra exhibiting more negative values. The duplex fuel yields a softer spectrum than the UO2 fuel with the candidate claddings, which improves neutron economy and thus discharge burnup

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio

Real-time selective sequencing using nanopore technology

The Oxford Nanopore Technologies MinION sequencer enables the selection of specific DNA molecules for sequencing by reversing the driving voltage across individual nanopores. To directly select molecules for sequencing, we used dynamic time warping to match reads to reference sequences. We demonstrate our open-source Read Until software in real-time selective sequencing of regions within small genomes, individual amplicon enrichment and normalization of an amplicon set

Large sub-clonal variation in <i>Phytophthora infestans</i> from recent severe late blight epidemics in India

Abstract The population structure of the Phytophthora infestans populations that caused the recent 2013–14 late blight epidemic in eastern India (EI) and northeastern India (NEI) was examined. The data provide new baseline information for populations of P. infestans in India. A migrant European 13_A2 genotype was responsible for the 2013–14 epidemic, replacing the existing populations. Mutations have generated substantial sub-clonal variation with 24 multi-locus genotypes (MLGs) found, of which 19 were unique variants not yet reported elsewhere globally. Samples from West Bengal were the most diverse and grouped alongside MLGs found in Europe, the UK and from neighbouring Bangladesh but were not linked directly to most samples from south India. The pathogen population was broadly more aggressive on potato than on tomato and resistant to the fungicide metalaxyl. Pathogen population diversity was higher in regions around the international borders with Bangladesh and Nepal. Overall, the multiple shared MLGs suggested genetic contributions from UK and Europe in addition to a sub-structure based on the geographical location within India. Our data indicate the need for improved phytosanitary procedures and continuous surveillance to prevent the further introduction of aggressive lineages of P. infestans into the country

Gene expression polymorphism underpins evasion of host immunity in an asexual lineage of the Irish potato famine pathogen

BACKGROUND: Outbreaks caused by asexual lineages of fungal and oomycete pathogens are a continuing threat to crops, wild animals and natural ecosystems (Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ, Nature 484:186-194, 2012; Kupferschmidt K, Science 337:636-638, 2012). However, the mechanisms underlying genome evolution and phenotypic plasticity in asexual eukaryotic microbes remain poorly understood (Seidl MF, Thomma BP, BioEssays 36:335-345, 2014). Ever since the 19th century Irish famine, the oomycete Phytophthora infestans has caused recurrent outbreaks on potato and tomato crops that have been primarily caused by the successive rise and migration of pandemic asexual lineages (Goodwin SB, Cohen BA, Fry WE, Proc Natl Acad Sci USA 91:11591-11595, 1994; Yoshida K, Burbano HA, Krause J, Thines M, Weigel D, Kamoun S, PLoS Pathog 10:e1004028, 2014; Yoshida K, Schuenemann VJ, Cano LM, Pais M, Mishra B, Sharma R, Lanz C, Martin FN, Kamoun S, Krause J, et al. eLife 2:e00731, 2013; Cooke DEL, Cano LM, Raffaele S, Bain RA, Cooke LR, Etherington GJ, Deahl KL, Farrer RA, Gilroy EM, Goss EM, et al. PLoS Pathog 8:e1002940, 2012). However, the dynamics of genome evolution within these clonal lineages have not been determined. The objective of this study was to use a comparative genomics and transcriptomics approach to determine the molecular mechanisms that underpin phenotypic variation within a clonal lineage of P. infestans. RESULTS: Here, we reveal patterns of genomic and gene expression variation within a P. infestans asexual lineage by comparing strains belonging to the South American EC-1 clone that has dominated Andean populations since the 1990s (Yoshida K, Burbano HA, Krause J, Thines M, Weigel D, Kamoun S, PLoS Pathog 10e1004028, 2014; Yoshida K, Schuenemann VJ, Cano LM, Pais M, Mishra B, Sharma R, Lanz C, Martin FN, Kamoun S, Krause J, et al. eLife 2:e00731, 2013; Delgado RA, Monteros-Altamirano AR, Li Y, Visser RGF, van der Lee TAJ, Vosman B, Plant Pathol 62:1081-1088, 2013; Forbes GA, Escobar XC, Ayala CC, Revelo J, Ordonez ME, Fry BA, Doucett K, Fry WE, Phytopathology 87:375-380, 1997; Oyarzun PJ, Pozo A, Ordonez ME, Doucett K, Forbes GA, Phytopathology 88:265-271, 1998). We detected numerous examples of structural variation, nucleotide polymorphisms and loss of heterozygosity within the EC-1 clone. Remarkably, 17 genes are not expressed in one of the two EC-1 isolates despite apparent absence of sequence polymorphisms. Among these, silencing of an effector gene was associated with evasion of disease resistance conferred by a potato immune receptor. CONCLUSIONS: Our findings highlight the molecular changes underpinning the exceptional genetic and phenotypic plasticity associated with host adaptation in a pandemic clonal lineage of a eukaryotic plant pathogen. We observed that the asexual P. infestans lineage EC-1 can exhibit phenotypic plasticity in the absence of apparent genetic mutations resulting in virulence on a potato carrying the Rpi-vnt1.1 gene. Such variant alleles may be epialleles that arose through epigenetic changes in the underlying genes

Potential new genes for resistance to Mycosphaerella graminicola identified in Triticum aestivum x Lophopyrum elongatum disomic substitution lines.

Lophopyrum species carry many desirable agronomic traits, including disease resistance, which can be transferred towheat by interspecific hybridization. To identify potentially new genes for disease and insect resistance carried by individual Lophopyrum chromosomes, 19 of 21 possible wheat cultivar Chinese Spring 9 Lophopyrum elongatum disomic substitution lines were tested for resistance to barley yellow dwarf virus (BYDV), cereal yellow dwarf virus (CYDV), the Hessian fly Mayetiola destructor, and the fungal pathogens Blumeria graminis and Mycosphaerella graminicola (asexual stage: Septoria tritici). Low resistance to BYDV occurred in some of the disomic substitution lines, but viral titers were significantly higher than those of two Lophopyrum species tested. This suggested that genes on more than one Lophopyrum chromosome are required for complete resistance to this virus. A potentially new gene for resistance to CYDV was detected on wheatgrass chromosome 3E. All of the substitution lines were susceptible to Mayetiola destructor and one strain of B. graminis. Disomic substitution lines containing wheatgrass chromosomes 1E and 6E were significantly more resistant to M. graminicola compared to Chinese Spring. Although neither chromosome by itself conferred resistance as high as that in the wheatgrass parent, they do appear to contain potentially new genes for resistance against this pathogen that could be useful for future plant-improvement programs

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Adaptation of cortical activity to sustained pressure stimulation on the fingertip

Background Tactile adaptation is a phenomenon of the sensory system that results in temporal desensitization after an exposure to sustained or repetitive tactile stimuli. Previous studies reported psychophysical and physiological adaptation where perceived intensity and mechanoreceptive afferent signals exponentially decreased during tactile adaptation. Along with these studies, we hypothesized that somatosensory cortical activity in the human brain also exponentially decreased during tactile adaptation. The present neuroimaging study specifically investigated temporal changes in the human cortical responses to sustained pressure stimuli mediated by slow-adapting type I afferents. Methods We applied pressure stimulation for up to 15 s to the right index fingertip in 21 healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. We analyzed cortical responses in terms of the degrees of cortical activation and inter-regional connectivity during sustained pressure stimulation. Results Our results revealed that the degrees of activation in the contralateral primary and secondary somatosensory cortices exponentially decreased over time and that intra- and inter-hemispheric inter-regional functional connectivity over the regions associated with tactile perception also linearly decreased or increased over time, during pressure stimulation. Conclusion These results indicate that cortical activity dynamically adapts to sustained pressure stimulation mediated by SA-I afferents, involving changes in the degrees of activation on the cortical regions for tactile perception as well as in inter-regional functional connectivity among them. We speculate that these adaptive cortical activity may represent an efficient cortical processing of tactile information.open