A haploid diamondback moth (Plutella xylostella L.) genome assembly resolves 31 chromosomes and identifies a diamide resistance mutation.

The diamondback moth, Plutella xylostella (L.), is a highly mobile brassica crop pest with worldwide distribution and can rapidly evolve resistance to insecticides, including group 28 diamides. Reference genomes assembled using Illumina sequencing technology have provided valuable resources to advance our knowledge regarding the biology, origin and movement of diamondback moth, and more recently with its sister species, Plutella australiana. Here we apply a trio binning approach to sequence and annotate a chromosome level reference genome of P. xylostella using PacBio Sequel and Dovetail Hi-C sequencing technology and identify a point mutation that causes resistance to commercial diamides. A P. xylostella population collected from brassica crops in the Lockyer Valley, Australia (LV-R), was reselected for chlorantraniliprole resistance then a single male was crossed to a P. australiana female and a hybrid pupa sequenced. A chromosome level 328 Mb P. xylostella genome was assembled with 98.1% assigned to 30 autosomes and the Z chromosome. The genome was highly complete with 98.4% of BUSCO Insecta genes identified and RNAseq informed protein prediction annotated 19,002 coding genes. The LV-R strain survived recommended field application doses of chlorantraniliprole, flubendiamide and cyclaniliprole. Some hybrids also survived these doses, indicating significant departure from recessivity, which has not been previously documented for diamides. Diamide chemicals modulate insect Ryanodine Receptors (RyR), disrupting calcium homeostasis, and we identified an amino acid substitution (I4790K) recently reported to cause diamide resistance in a strain from Japan. This chromosome level assembly provides a new resource for insect comparative genomics and highlights the emergence of diamide resistance in Australia. Resistance management plans need to account for the fact that resistance is not completely recessive.

In vitro evaluation of root canal wall cleanliness in primary molars after preparation with Self-Adjusting-File (SAF) or Mtwo NiTi-instruments and final irrigation.

AIM: In vitro evaluation of cleanliness of root canal walls of primary molars after preparation with the Self-Adjusting-File and Mtwo-instruments and final irrigation with citric acid and sodium hypochlorite. MATERIALS AND METHODS: s Study Design: In 23 matched pairs, teeth were prepared either with SAF or with Mtwo NiTi-instruments, and final irrigation was performed with 2 mL citric acid and 4 mL NaOCl. Roots were split longitudinally, SEM-images were taken, and smear layer was evaluated by two blinded observers using a four-grade score. Statistical evaluation was performed with Mann-Whitney-U-Test and Wilcoxon Signed Rank Test (P<0.05). RESULTS: No significant difference between SAF and Mtwo (P=0.9454) was observed. Overall removal of the smear layer was significantly better in the coronal part of the root canal than in the apical one (P=0.0004393). Mtwo showed no significant difference in cleanliness when comparing the coronal and apical part of the root canal (P=0.1089), whereas SAF cleaned the coronal part of the root canal significantly better than the apical part (P=0.00108). CONCLUSION: None of the two instruments was superior concerning cleanliness in root canals of primary molars. Both show good cleaning ability when using an irrigation protocol with citric acid and sodium hypochlorite.

Impact of Recurrence Score on type and duration of chemotherapy in breast cancer.

Background: The use of Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) testing has been shown to change treatment decisions in approximately 30% of breast cancer (bca) cases, but research on how Recurrence Score testing has affected the type of chemotherapy offered is limited. We sought to determine if the availability of Oncotype dx testing resulted in a change to the type and duration of chemotherapy regimens used in the treatment of early-stage hormone receptor-positive bca. Methods: In a population-based cohort study, patients treated in the 2 years before the availability of Oncotype dx testing were compared with patients treated in the 2 years after testing availability. Charts were audited and divided into 2 groups: pre-Oncotype dx and post-Oncotype dx. The groups were compared for differences in duration of chemotherapy (12 weeks vs. >12 weeks), types of agents used (anthracycline vs. non-anthracycline), and myelosuppressive potential of the chosen regimen. Results: Of 834 patients who fulfilled the enrolment criteria, 360 fell into the pre-Oncotype dx era, and 474, into the post-Oncotype dx era. An increase of 11.2 percentage points, to 69.5% from 58.3%, was observed in the proportion of patients receiving short-course compared with long-course chemotherapy (p = 0.068). The proportion of patients prescribed anthracycline-containing regimens declined in the post-Oncotype dx era (47.7% pre vs. 32.2% post, p = 0.016). The selection of more-myelosuppressive chemotherapy protocols increased in the post-Oncotype dx era (67.4% pre vs. 78.8% post, p = 0.044). Conclusions: In the present study, the availability of Oncotype dx testing was observed to influence the choice of chemotherapy type in the setting of early-stage bca.

Micro-CT evaluation of sonically and ultrasonically activated irrigation on the removal of hard-tissue debris from isthmus-containing mesial root canal systems of mandibular molars.

AIM: To evaluate the efficacy of sonically and ultrasonically activated irrigation on removal of accumulated hard-tissue debris (AHTD) in mesial root canal systems of mandibular molars using micro-computed tomographic (micro-CT) analysis. METHODOLOGY: Forty mesial roots of mandibular molars with two independent canals joined apically by an isthmus (Vertucci type II) were selected. The root canals were instrumented using Reciproc R25 instruments, and specimens were scanned at a resolution of 10.5 µm. Subsequently, n = 10 roots were assigned to each of the four final irrigation groups such that the group means and variances were almost identical: sonically activated irrigation with EndoActivator (EA) or EDDY (ED), ultrasonically activated irrigation (UAI) and manual irrigation without activation (MI). The final irrigation procedures were performed using a total of 5 mL 1% NaOCl and 5 mL 15% EDTA per canal over 5 min with activation time of 4 × 20 s. Reconstructed data sets were coregistered, and the mean percentage reduction of AHTD after final irrigation was compared statistically between groups using analysis of variance at a significance level set at 5%. RESULTS: A significant reduction of AHTD was achieved after final irrigation in all groups (P < 0.05), ranging from 44.1% to 66.8%. The vol% of debris after irrigation was 3.7 ± 1.9% for EA, 3.3 ± 2.3% for ED, 2.1 ± 1.6% for UAI and 4.4 ± 2.3% for MI, with no significant difference between groups (P > 0.05). CONCLUSIONS: None of the final irrigation protocols completely removed AHTD from mesial root canal systems in extracted human mandibular molars. Sonically and ultrasonically activated irrigation performed no better compared to manual irrigation.

Parameterizing developmental changes in epistemic trust.

Children rely on others for much of what they learn, and therefore must track who to trust for information. Researchers have debated whether to interpret children's behavior as inferences about informants' knowledgeability only or as inferences about both knowledgeability and intent. We introduce a novel framework for integrating results across heterogeneous ages and methods. The framework allows application of a recent computational model to a set of results that span ages 8 months to adulthood and a variety of methods. The results show strong fits to specific findings in the literature trust, and correctly fails to fit one representative result from an adjacent literature. In the aggregate, the results show a clear development in children's reasoning about informants' intent and no appreciable changes in reasoning about informants' knowledgeability, confirming previous results. The results extend previous findings by modeling development over a much wider age range and identifying and explaining differences across methods.

EB Ford revisited: assessing the long-term stability of wing-spot patterns and population genetic structure of the meadow brown butterfly on the Isles of Scilly.

Understanding selection in the wild remains a major aim of evolutionary ecology and work by Ford and colleagues on the meadow brown butterfly Maniola jurtina did much to ignite this agenda. A great deal of their work was conducted during the 1950s on the Isles of Scilly. They documented island-specific wing-spot patterns that remained consistent over about a decade, but patterns on some islands changed after environmental perturbation. It was suggested that these wing-spot patterns reflected island-specific selection and that there was little migration between islands. However, genetic studies to test the underlying assumption of restricted migration are lacking and it is also unknown whether the originally described wing-spot patterns have persisted over time. We therefore collected female butterflies from five of Ford's original study locations, including three large islands (St Mary's, St Martin's and Tresco) and two small islands (Tean and St Helen's). Wing-spot patterns had not changed appreciably over time on three of the islands (two large and one small), but were significantly different on the other two. Furthermore, analysis of 176 amplified fragment length polymorphisms revealed significant genome-wide differentiation among the five islands. Our findings are consistent with Ford's conclusions that despite the close proximity of these islands, there is restricted gene flow among them.

Cognitive ability, social desirability, body mass index and socioeconomic status as correlates of fourth-grade children's dietary-reporting accuracy.

BACKGROUND/OBJECTIVES: To investigate the relationship of reporting accuracy in 24-h dietary recalls to child-respondent characteristics-cognitive ability, social desirability, body mass index (BMI) percentile and socioeconomic status (SES). SUBJECTS/METHODS: Fourth-grade children (mean age 10.1 years) were observed eating two school meals and interviewed about dietary intake for 24 h that included those meals. (Eight multiple-pass interview protocols operationalized the conditions of an experiment that crossed two retention intervals-short and long-with four prompts (ways of eliciting reports in the first pass)). Academic achievement-test scores indexed cognitive ability; social desirability was assessed by questionnaire; height and weight were measured to calculate BMI; nutrition-assistance program eligibility information was obtained to index SES. Reported intake was compared to observed intake to calculate measures of reporting accuracy for school meals at the food-item (omission rate; intrusion rate) and energy (correspondence rate; inflation ratio) levels. Complete data were available for 425 of 480 validation-study participants. RESULTS: Controlling for manipulated variables and other measured respondent characteristics, for one or more of the outcome variables, reporting accuracy increased with cognitive ability (omission rate, intrusion rate, correspondence rate, P<0.001), decreased with social desirability (correspondence rate, P<0.0004), decreased with BMI percentile (correspondence rate, P=0.001) and was better by higher- than by lower-SES children (intrusion rate, P=0.001). Some of these effects were moderated by interactions with retention interval and sex. CONCLUSIONS: Children's dietary-reporting accuracy is systematically related to such respondent characteristics as cognitive ability, social desirability, BMI percentile and SES.

Infant-directed speech is consistent with teaching.

Infant-directed speech (IDS) has distinctive properties that differ from adult-directed speech (ADS). Why it has these properties-and whether they are intended to facilitate language learning-is a matter of contention. We argue that much of this disagreement stems from lack of a formal, guiding theory of how phonetic categories should best be taught to infantlike learners. In the absence of such a theory, researchers have relied on intuitions about learning to guide the argument. We use a formal theory of teaching, validated through experiments in other domains, as the basis for a detailed analysis of whether IDS is well designed for teaching phonetic categories. Using the theory, we generate ideal data for teaching phonetic categories in English. We qualitatively compare the simulated teaching data with human IDS, finding that the teaching data exhibit many features of IDS, including some that have been taken as evidence IDS is not for teaching. The simulated data reveal potential pitfalls for experimentalists exploring the role of IDS in language learning. Focusing on different formants and phoneme sets leads to different conclusions, and the benefit of the teaching data to learners is not apparent until a sufficient number of examples have been provided. Finally, we investigate transfer of IDS to learning ADS. The teaching data improve classification of ADS data but only for the learner they were generated to teach, not universally across all classes of learners. This research offers a theoretically grounded framework that empowers experimentalists to systematically evaluate whether IDS is for teaching. (PsycINFO Database Record

Promoting and maintaining physical activity in the transition to retirement: a systematic review of interventions for adults around retirement age.

It has been argued that transition points in life, such as the approach towards, and early years of retirement present key opportunities for interventions to improve the health of the population. Research has also highlighted inequalities in health status in the retired population and in response to interventions which should be addressed. We aimed to conduct a systematic review to synthesise international evidence on the types and effectiveness of interventions to increase physical activity among people around the time of retirement. A systematic review of literature was carried out between February 2014 and April 2015. Searches were not limited by language or location, but were restricted by date to studies published from 1990 onwards. Methods for identification of relevant studies included electronic database searching, reference list checking, and citation searching. Systematic search of the literature identified 104 papers which described study populations as being older adults. However, we found only one paper which specifically referred to their participants as being around the time of retirement. The intervention approaches for older adults encompassed: training of health care professionals; counselling and advice giving; group sessions; individual training sessions; in-home exercise programmes; in-home computer-delivered programmes; in-home telephone support; in-home diet and exercise programmes; and community-wide initiatives. The majority of papers reported some intervention effect, with evidence of positive outcomes for all types of programmes. A wide range of different measures were used to evaluate effectiveness, many were self-reported and few studies included evaluation of sedentary time. While the retirement transition is considered a significant point of life change, little research has been conducted to assess whether physical activity interventions at this time may be effective in promoting or maintaining activity, or reducing health inequalities. We were unable to find any evidence that the transition to retirement period was, or was not a significant point for intervention. Studies in older adults more generally indicated that a range of interventions might be effective for people around retirement age.

'Thin people they're healthy': young children's understanding of body weight change.

BACKGROUND: While research has investigated negative stereotyping of fat body shapes, little has focused on young children's understanding of the mechanisms, motivations and consequences of weight change. OBJECTIVES: To investigate children's understanding of how weight change is achieved, people's motivation for weight change, and the consequences of weight loss or weight gain. METHODS: One hundred children (mean age 5.2, 38 girls) read a book in which one of the main characters (male/female according to the child's sex) was either healthy weight or overweight. Afterwards, this character was described as gaining or losing weight, and drawings which depicted the child in the story as either healthy weight or overweight were presented to the child and discussed. An audio-recorded semi-structured interview followed and transcripts were analysed using thematic analysis. RESULTS: Nearly all children described the weight/shape change and attributed this to food more frequently than exercise. Weight loss was viewed positively and both motivations and consequences grouped under two master themes (physical and social reasons). No clear gender differences were observed in these responses. CONCLUSIONS: Talking with 5-year-olds showed them to be observant and knowledgeable, especially about motivations for and consequences of weight change. For those working to improve children's health literacy, this suggests receptiveness to early and fact-based education.

Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies.

Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima.

Learning to trust and trusting to learn: a theoretical framework.

Learning from other people requires integrating reasoning about an informant's psychological properties, such as knowledge and intent, with reasoning about the implications of the data the informant chooses to present. Here, we argue for an approach that considers these two reasoning paths as interrelated, reciprocal processes that develop over experience and guide learners when acquiring knowledge about the world.

Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response.

Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical interventions, which act mainly by regulating gene expression levels. A large fraction of patients (∼30%), especially those of African descent, show a weak response to treatment. To interrogate the contribution of variable transcriptional response to inter-ethnic differences, we measured in vitro lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in peripheral blood mononuclear cells from African-American (AA) and European-American (EA) healthy donors. We found that transcriptional response after 8 h treatment was significantly correlated with variation in LGS within and between populations. We found that NFKB1, a gene previously found to predict LGS within populations, was more strongly downregulated in EAs on average. NFKB1 could not completely explain population differences, however, and we found an additional 177 genes with population differences in the average log2 fold change (false discovery rate<0.05), most of which also showed a weaker transcriptional response in AAs. These results suggest that inter-ethnic differences in GC sensitivity reflect variation in transcriptional response at many genes, including regulators with large effects (for example, NFKB1) and numerous other genes with smaller effects.

Unifying pedagogical reasoning and epistemic trust.

Researchers have argued that other people provide not only great opportunities for facilitating children's learning but also great risks. Research on pedagogical reasoning has argued children come prepared to identify and capitalize on others' helpfulness to teach, and this pedagogical reasoning allows children to learn rapidly and robustly. In contrast, research on epistemic trust has focused on how the testimony of others is not constrained to be veridical, and therefore, children must be prepared to identify which informants to trust for information. Although these problems are clearly related, these two literatures have, thus far, existed relatively independently of each other. We present a formal analysis of learning from informants that unifies and fills gaps in each of these literatures. Our analysis explains why teaching--learning from a knowledgeable and helpful informant--supports more robust inferences. We show that our account predicts specific inferences supported in pedagogical situations better than a standard account of learning from teaching. Our analysis also suggests that epistemic trust should depend on inferences about others' knowledge and helpfulness. We show that our knowledge and helpfulness account explains children's behavior in epistemic trust tasks better than the standard knowledge-only account. We conclude by discussing implications for development and outline important questions raised by viewing learning from testimony as joint inference over others' knowledge and helpfulness.

Long-term outcome in an uncemented, hydroxyapatite-coated total knee replacement: a 15- to 18-year survivorship analysis.

A consecutive series of patients with a hydroxyapatite-coated uncemented total knee replacement (TKR) performed by a single surgeon between 1992 and 1995 was analysed. All patients were invited for clinical review and radiological assessment. Revision for aseptic loosening was the primary outcome. Assessment was based on the Knee Society clinical score (KSS) and an independent radiological analysis. Of 471 TKRs performed in 356 patients, 432 TKRs in 325 patients were followed for a mean of 16.4 years (15 to 18). The 39 TKRs in 31 patients lost to follow-up had a mean KSS of 176 (148 to 198) at a mean of ten years. There were revisions in 26 TKRs (5.5%), of which 11 (2.3%) were for aseptic loosening. Other further surgery was carried out on 49 TKRs (10.4%) including patellar resurfacing in 20, arthrolysis in 19, manipulation under anaesthetic in nine and extensor mechanism reconstruction in one. Survivorship at up to 18 years without aseptic loosening was 96% (95% confidence interval 91.9 to 98.1), at which point the mean KSS was 176 (134 to 200). Of 110 knees that underwent radiological evaluation, osteolysis was observed in five (4.5%), one of which was revised. These data indicate that uncemented hydroxyapatite-coated TKR can achieve favourable long-term survivorship, at least as good as that of cemented designs.

Citizens advice in primary care: a qualitative study of the views and experiences of service users and staff.

OBJECTIVES: To examine the views and experiences of staff and users of Citizens Advice Bureau (CAB) services located in general practice, and to identify key factors perceived as contributing to the intervention's effectiveness. STUDY DESIGN: A qualitative study in an urban and rural primary care setting in the UK. METHODS: Semi-structured, face-to-face interviews (n = 22) with primary care and practice staff, CAB advisors and 12 service users. RESULTS: Key positive service features reported by all groups were: the confidential, non-stigmatizing and familiar environment of a general practitioner's (GP) surgery; the ability to make appointments and experienced advisor availability and continuity. Outcomes for service users were described as financial gain, managed debt, and beneficial social and mental health impacts. Perceived staff benefits were appropriate referral and better use of GP consultation time. CONCLUSION: Welfare advice in primary care has financial benefits and was perceived by participants to offer health and other benefits to patients and staff. However, while perceptions of gain from the intervention were evident, demonstration of measurable health improvement and well-being presents challenges. Further empirical work is needed in order to explore these complex cause-effect links and the cost-effectiveness of the intervention.

Comparative population genetics of a mimicry locus among hybridizing Heliconius butterfly species.

The comimetic Heliconius butterfly species pair, H. erato and H. melpomene, appear to use a conserved Mendelian switch locus to generate their matching red wing patterns. Here we investigate whether H. cydno and H. pachinus, species closely related to H. melpomene, use this same switch locus to generate their highly divergent red and brown color pattern elements. Using an F2 intercross between H. cydno and H. pachinus, we first map the genomic positions of two novel red/brown wing pattern elements; the G locus, which controls the presence of red vs brown at the base of the ventral wings, and the Br locus, which controls the presence vs absence of a brown oval pattern on the ventral hind wing. The results reveal that the G locus is tightly linked to markers in the genomic interval that controls red wing pattern elements of H. erato and H. melpomene. Br is on the same linkage group but approximately 26 cM away. Next, we analyze fine-scale patterns of genetic differentiation and linkage disequilibrium throughout the G locus candidate interval in H. cydno, H. pachinus and H. melpomene, and find evidence for elevated differentiation between H. cydno and H. pachinus, but no localized signature of association. Overall, these results indicate that the G locus maps to the same interval as the locus controlling red patterning in H. melpomene and H. erato. This, in turn, suggests that the genes controlling red pattern elements may be homologous across Heliconius, supporting the hypothesis that Heliconius butterflies use a limited suite of conserved genetic switch loci to generate both convergent and divergent wing patterns.

Widespread pyrethroid resistance in Australian diamondback moth, Plutella xylostella (L.), is related to multiple mutations in the para sodium channel gene.

Populations of Plutella xylostella, extending over 3800 km in southern Australia, show no genetic structure as assessed by microsatellite markers; yet outbreaks of pyrethroid resistance occur sporadically in cropping areas. Since mutations in the para voltage-gated sodium channel gene have been implicated in pyrethroid resistance, we looked for DNA sequence variation at this target among Australian moths. We found two resistance mutations previously reported for this species (L1014F and T929I), as well as a novel substitution (F1020S). Of the eight possible haplotypes formed by combinations of these three biallelic polymorphisms, only four were found in Australian populations: the wild-type allele (w), the kdr mutation allele (kdr) with only L1014F, the super-kdr-like combination of L1014F and T929I (skdrl), and the crashdown allele with only F1020S (cdr). Comparison of genotype frequencies among survivors of permethrin assays with those from untreated controls identified three resistant genotypes: skdrl homozygotes, cdr homozygotes and the corresponding heterozygote, cdr/skrdl - the heterozygote being at least as resistant as either homozygote. Spatial heterogeneity of allele frequencies was conspicuous, both across the continent and among local collections, consistent with reported spatial heterogeneity of pyrethroid resistance. Further, high resistance samples were sometimes associated with high frequency of cdr, sometimes high frequency of skdrl, or sometimes with a high combined cdr+skdrl frequency. The skdrl and cdr alleles explain a high proportion of the Australia-wide resistance variation. These data add to evidence that nerve insensitivity by mutations in the para-sodium channel gene is a common pyrethroid resistance mechanism in P. xylostella.