Potential application of immunotherapy for modulation of pulp inflammation: opportunities for vital pulp treatment.

Caries results in the demineralization and destruction of enamel and dentine, and as the disease progresses, irreversible pulpitis can occur. Vital pulp therapy (VPT) is directed towards pulp preservation and the prevention of the progression of inflammation. The outcomes of VPT are not always predictable, and there is often a poor correlation between clinical signs and symptoms, and the events occurring at a molecular level. The inflamed pulp expresses increased levels of cytokines, including tumour necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-8, IL-17 and IL-23, which recruit and drive a complex cellular immune response. Chronic inflammation and sustained cytokine release can result in irreversible pulp damage and a decreased capacity for tissue healing. Other chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases and rheumatoid arthritis, are also characterized by an dysregulated immune response composed of relatively high cytokine levels and increased numbers of immune cells along with microbial and hard-soft tissue destructive pathologies. Whilst anti-cytokine therapies have been successfully applied in the treatment of these diseases, this approach is yet to be attempted in cases of pulp inflammation. This review therefore focuses on the similarities in the aetiology between chronic inflammatory diseases and pulpitis, and explores how anti-cytokine therapies could be applied to manage an inflamed pulp and facilitate healing. Further proof-of-concept studies and clinical trials are justified to determine the effectiveness of these treatments to enable more predictable outcomes in VPT.

Automated, unsupervised inversion of multiwavelength lidar data with TiARA: assessment of retrieval performance of microphysical parameters using simulated data.

We evaluate the retrieval performance of the automated, unsupervised inversion algorithm, Tikhonov Advanced Regularization Algorithm (TiARA), which is used for the autonomous retrieval of microphysical parameters of anthropogenic and natural pollution particles. TiARA (version 1.0) has been developed in the past 10 years and builds on the legacy of a data-operator-controlled inversion algorithm used since 1998 for the analysis of data from multiwavelength Raman lidar. The development of TiARA has been driven by the need to analyze in (near) real time large volumes of data collected with NASA Langley Research Center's high-spectral-resolution lidar (HSRL-2). HSRL-2 was envisioned as part of the NASA Aerosols-Clouds-Ecosystems mission in response to the National Academy of Sciences (NAS) Decadal Study mission recommendations 2007. TiARA could thus also serve as an inversion algorithm in the context of a future space-borne lidar. We summarize key properties of TiARA on the basis of simulations with monomodal logarithmic-normal particle size distributions that cover particle radii from approximately 0.05 µm to 10 µm. The real and imaginary parts of the complex refractive index cover the range from non-absorbing to highly light-absorbing pollutants. Our simulations include up to 25% measurement uncertainty. The goal of our study is to provide guidance with respect to technical features of future space-borne lidars, if such lidars will be used for retrievals of microphysical data products, absorption coefficients, and single-scattering albedo. We investigate the impact of two different measurement-error models on the quality of the data products. We also obtain for the first time, to the best of our knowledge, a statistical view on systematic and statistical uncertainties, if a large volume of data is processed. Effective radius is retrieved to 50% accuracy for 58% of cases with an imaginary part up to 0.01i and up to 100% of cases with an imaginary part of 0.05i. Similarly, volume concentration, surface-area concentration, and number concentrations are retrieved to 50% accuracy in 56%-100% of cases, 99%-100% of cases, and 54%-87% of cases, respectively, depending on the imaginary part. The numbers represent measurement uncertainties of up to 15%. If we target 20% retrieval accuracy, the numbers of cases that fall within that threshold are 36%-76% for effective radius, 36%-73% for volume concentration, 98%-100% for surface-area concentration, and 37%-61% for number concentration. That range of numbers again represents a spread in results for different values of the imaginary part. At present, we obtain an accuracy of (on average) 0.1 for the real part. A case study from the ORCALES field campaign is used to illustrate data products obtained with TiARA.

FoxP3+ regulatory T cells, interleukin 17 and mast cells in chronic inflammatory periodontal disease.

BACKGROUND AND OBJECTIVE: T cells are known to play a pivotal role in periodontal disease; however, less is known about the T-helper subsets of regulatory T cells (Tregs) and Th17 cells. The aim of this study was to investigate the cell types expressing FoxP3 and interleukin (IL)-17A within periodontal disease tissues and to determine gene and protein expression profiles associated with periodontitis. MATERIAL AND METHODS: A total of 10 healthy/gingivitis and 10 chronic periodontitis tissues were investigated. Immunohistochemistry and immunofluorescence techniques were used to identify the FoxP3 and IL17-positive cells and to determine the cell types respectively. Gene expression was determined using semi-quantitative polymerase chain reaction array technology that allowed the analysis of 84 pathway-focused genes known to be associated with Tregs and Th17 cells. Transforming growth factor (TGF)-ß1, IL10 and IL17A protein levels were determined using enzyme-linked immunosorbent assay. RESULTS: Double immunofluorescence labeling revealed that all FoxP3+ cells were CD4+ , while IL17+ cells were neither CD4+ nor CD8+ but were tryptase+ , suggestive of mast cells. More FoxP3+ cells than IL17+ cells were found in all the tissues examined and overall there were few IL17+ cells. Statistically significant increases in gene expression were found for STAT5A, STAT3, SOCS1, TGFß1 and IL10 in the chronic periodontitis specimens predominantly infiltrated with B cells and plasma cells when compared with healthy/gingivitis specimens predominantly infiltrated with T cells. Protein analysis demonstrated higher levels of the TGFß1 and IL10 cytokines in periodontitis tissues and in B-cell and plasma cell predominant gingival tissues than in healthy/gingivitis tissues and T-cell predominant gingival tissues. IL17A gene and protein expression was not detected in any of the tissues. CONCLUSION: Based on the findings of this study, we suggest that the source of low levels of IL17A in periodontal tissues is mast cells not Th17 cells and that Tregs may have a more prominent role in the pathogenesis of periodontal disease than Th17 cells.

Upregulation of angiogenesis in oral lichen planus.

OBJECTIVES: As angiogenesis is fundamental to the pathogenesis of many chronic inflammatory disorders, this study investigated the expression of various vascular markers in oral lichen planus and non-specific oral mucosal inflammatory tissues. METHODS: Archival specimens of oral lichen planus (n = 15) and inflamed tissues (n = 13) were stained using immunohistochemistry with antibodies to CD34, vascular endothelial growth factor, vascular endothelial growth factor receptor and vasohibin. Nine representative sites at the epithelial-connective tissue junction and through the fibrous connective tissue were selected, and automated analysis techniques were used to determine the extent of positivity expressed as the percentage of positive cells. Significance was denoted when P < .05. RESULTS: The expression of pro-angiogenic factors was higher in lichen planus samples compared with inflamed controls. A higher level of CD34 was observed in the deeper parts of the connective tissue of Oral lichen planus (OLP) (P = .04), whereas VEGF and VEGFR2 expressions were higher all through the tissues (respectively, P < .02 and P < .01). The expression of the anti-angiogenic VASH1 was higher in inflamed tissue compared with lichen planus in all sites evaluated (P < .01). CONCLUSIONS: The findings indicate that angiogenic factors are differentially expressed in oral lichen planus compared with inflamed controls, with increased expression of pro-angiogenic factors and decreased anti-angiogenic expression.

Effectiveness of an oral health education seminar for paediatric and family medicine residents.

AIM: To assess the immediate effect of a 60-minute oral health educational seminar for paediatric and family medicine residents in improving their knowledge, attitude, likelihoodtowards incorporating oral health preventive practice in their current practices to well-child visits, and confidence in identifying and referring patients with dental trauma. MATERIALS AND METHODS: Baseline pre- and post-test design was used to evaluate the immediate effect of a 60-minute PowerPoint oral health educational seminar given to the paediatric and family medicine residents. STATISTICS: Multiple-choice items were used and the pre- and post-test data were analysed with McNemar and Wilcoxon signed-rank tests. A p-value <0.05 was considered statistically significant. RESULTS: Sixty-eight residents participated in the oral health educational seminar and completed the questionnaire. The mean age of participants was 29.9 years old (SD ±4.8 yrs.). Immediately following a 60-minute oral health educational seminar, there was an overall significant increase in participants' knowledge, attitudes and likelihood towards incorporating oral health preventive practice in their current practices to well-child visits (p<0.05). More confidence in identifying and referring patients with dental trauma was reported by 100% of participants. CONCLUSIONS: A 60-minute oral health educational seminar was effective in improving paediatric and family medicine residents' immediate knowledge, attitude, and likelihood towards incorporating oral health preventive practice in their current practices to well-child visits. Significantly more residents felt more confident in identifying and referring patients with dental trauma. Key messages: an oral health educational seminar can be effective in improving paediatric and family medicine residents' immediate knowledge, attitude, and likelihood towards incorporating oral health preventive practice in their current practices to well-child visits.

Does age matter? Sexual event-level analysis of age-disparate sexual partners among gay, bisexual and other men who have sex with men (GBM) in Vancouver, Canada.

BACKGROUND: To determine factors associated with age-disparate sexual partners among Vancouver gay, bisexual and other men who have sex with men (GBM). METHODS: Sexually active GBM aged ≥16 years were recruited from February 2012 to February 2014. Participants self-completed a questionnaire on demographics, attitudes and sexual behaviour and substance use at last sexual event with five most recent partners. Two generalised linear mixed models identified factors associated with: (1) 'same-age' (referent), 'younger' or 'much-younger' and (2) 'same-age' (referent), 'older' or 'much-older' partners. Statistical interactions between age and HIV status were tested. RESULTS: Participants (n=719) were predominantly gay (85.1%), White (75.0%), HIV-negative/unknown status (72.9%) with median age of 33 years (Q1,Q3: 26,47). A minority of sexual events were reported with much-older/much-younger partners (13.7%). In the multivariable models, GBM reporting older partners were more likely to be Asian or Latino, have greater Escape Motivation scores, report their partner used erectile dysfunction drugs (EDDs) and have received something for sex; compared with condom-protected insertive anal sex, participants with older partners were more likely to report condomless insertive anal sex with a serodiscordant or unknown status partner or no insertive anal sex. GBM reporting older partners were less likely to be bisexual-identified, have given something for sex and report event-level alcohol and EDD use. GBM reporting younger partners were more likely to have annual incomes >$30 000 and have met their partner online. As per significant statistical interactions, age-disparate relations were more common for younger HIV-positive and older HIV-negative GBM. CONCLUSIONS: Differences among age-disparate partners highlight important targets for health promotion and future research.

The Representation of Color across the Human Visual Cortex: Distinguishing Chromatic Signals Contributing to Object Form Versus Surface Color.

Many theories of visual object perception assume the visual system initially extracts borders between objects and their background and then "fills in" color to the resulting object surfaces. We investigated the transformation of chromatic signals across the human ventral visual stream, with particular interest in distinguishing representations of object surface color from representations of chromatic signals reflecting the retinal input. We used fMRI to measure brain activity while participants viewed figure-ground stimuli that differed either in the position or in the color contrast polarity of the foreground object (the figure). Multivariate pattern analysis revealed that classifiers were able to decode information about which color was presented at a particular retinal location from early visual areas, whereas regions further along the ventral stream exhibited biases for representing color as part of an object's surface, irrespective of its position on the retina. Additional analyses showed that although activity in V2 contained strong chromatic contrast information to support the early parsing of objects within a visual scene, activity in this area also signaled information about object surface color. These findings are consistent with the view that mechanisms underlying scene segmentation and the binding of color to object surfaces converge in V2.

Political Affiliation, Probable PTSD, and Symptoms of Depression in Iraq and Afghanistan Combat Veterans: A Pilot Study.

Ideological commitment of military personnel has been associated with mitigating trauma and protecting mental health. This pilot study assessed whether Democratic and Republican political affiliation differentially predicted probable posttraumatic stress disorder (PTSD) and symptoms of depression in 62 male Iraq and Afghanistan combat veterans. The Liberalism-Conservatism Scale, the PTSD Checklist-Military Version (PCL-M), and the Patient Health Questionnaire-9 (PHQ-9) were assessment measures. Results revealed that Democratic combat veterans had stronger liberal attitudes than Republican combat veterans (r = 0.95). Moreover, of the 50% of the entire sample higher than the cutoff score of 50 on the PCL-M, 84.8% were Democrats compared with 10.3% of Republicans. On the PHQ-9, 46.9% of Democrats compared with 3.7% of Republicans were higher than the cutoff score of 20. These initial results suggest possible mechanisms of action, including differences in shattered world view assumptions, willingness to disclose emotional concerns, and physiological reactions between Democratic and Republican combat veterans.

A clinical trial of a novel emulsion for potential use as a saliva substitute in patients with radiation-induced xerostomia.

Researchers have recently developed a novel oily formulation for potential use as a saliva substitute for the treatment of dry mouth. The aim of this randomised, crossover study was to compare this new formulation to a currently available saliva substitute and a control of water on measures of mastication, subjective feeling of oral dryness and product acceptability. Forty participants treated with radiotherapy to the head and neck and experiencing xerostomia were invited to participate in the trial. Each participant trialled all three products in a randomised order. The effect of each product was measured using the Test of Masticating and Swallowing Solids (TOMASS), the Shortened Xerostomia Inventory (SXI) and a questionnaire designed to test patient acceptability of each product. Outcome data were gathered in a single session after the first administration of each product to evaluate immediate effects and after 7 days of use to evaluate longer-term effects. Statistical analyses consisted of repeated-measures analysis of variance and mixed models. There was no evidence that application of the three formulations had an effect on any of the TOMASS measures, either immediately or after one week of use (P > 0·05). There was a significant main effect of formulation on the SXI score (P = 0·02). Application of the novel emulsion resulted in a clinically small but significant improvement in SXI score (P < 0·01); however, application of methylcellulose (P = 0·21) and water (P = 0·81) resulted in no significant difference. There was no difference in participant acceptability between the three products (P = 0·32). The novel oily emulsion showed no clinically significant benefit over two existing products for relief of xerostomia. Indeed, none of the three products demonstrated significant change in patient outcomes.

Reasons of repeat dental treatment under general anaesthesia: A retrospective study.

AIM: The purpose of this chart review study was to investigate the common factors that exist in paediatric patients requiring a repeat dental treatment under general anaesthesia (GA2) within four years after the initial dental treatment under general anaesthesia (GA1). MATERIALS AND METHODS: The Electronic Health Records of one to 12 year-old children who received dental treatment under general anaesthesia (GA) between April 2004 and October 2009 were identified and analysed by a single examiner. Children who had GA2, within a four year period following GA1 were categorised as cases. Children who had only one dental treatment under GA were considered the control pool. Each case was matched to three controls based on sex and age range at GA1 of ± 6 months. Other recorded variables included: date of birth, date of GAs (GA1 and GA2 for cases; GA1 for controls), type of payment, dmfs before GA1, dental treatments provided under GA, return of 1-week post-GA1 follow-up, frequency of recare/recall visits following one-year post-GA1 visit and the type and frequency of post GA1 emergency visits. RESULTS: Out of 581 subjects, 29 (4.99%) cases were matched to 87 controls. Medically compromised patients had four times the risk of GA2. At GA1, cases received statistically significant less sealants (p=0.026), less extractions (p<0.0001), and more composite restorations (p=0.0002) compared to controls. CONCLUSION: Medically compromised children and children treated with more composites and fewer sealants and extractions at their initial dental treatment under general anaesthesia were more likely to have a repeat dental treatment under general anaesthesia within 4 years.

Awareness and use of nonoccupational post-exposure prophylaxis among men who have sex with men in Vancouver, Canada.

OBJECTIVES: Nonoccupational post-exposure prophylaxis (nPEP) is a strategy to reduce the risk of HIV infection in those with high-risk exposure. This study characterized nPEP awareness among gay, bisexual and other men who have sex with men (MSM) in Metro Vancouver, British Columbia, Canada after a pilot nPEP programme established in 2012. METHODS: Momentum Health Study participants were MSM aged ≥16 years recruited via respondent-driven sampling (RDS) who completed a computer-assisted self-interview. Stratifying patients by HIV status, we used multivariable logistic regression with backward selection to identify factors associated with nPEP awareness. All analyses were RDS-adjusted. RESULTS: A total of 51.9% (112 of 173) of HIV-positive and 48.5% (272 of 500) of HIV-negative participants had heard of nPEP. Only 3% (five of 106) of HIV-negative participants who reported recent high-risk sex used nPEP. Generally, nPEP awareness was higher for participants who engaged in sexual activities with increased HIV transmission potential. Factors associated with greater awareness among HIV-negative participants included recent alcohol use, higher communal sexual altruism, previous sexually transmitted infection diagnosis, and greater perceived condom use self-efficacy. Other factors associated with greater awareness among HIV-negative participants included white race/ethnicity, gay sexual identity, more formal education, lower personal sexual altruism, and Vancouver residence. Greater nPEP awareness among HIV-positive participants was associated with greater perceived agency to ask sexual partners' HIV status and more frequently reporting doing so, a higher number of lifetime receptive sex partners, and greater access to condoms. CONCLUSIONS: Following implementation of an nPEP pilot programme, nPEP awareness among HIV-negative MSM was 51% and use was 3%. These data support the need to expand access to and actively promote nPEP services.

Air quality implications of the Deepwater Horizon oil spill.

During the Deepwater Horizon (DWH) oil spill, a wide range of gas and aerosol species were measured from an aircraft around, downwind, and away from the DWH site. Additional hydrocarbon measurements were made from ships in the vicinity. Aerosol particles of respirable sizes were on occasions a significant air quality issue for populated areas along the Gulf Coast. Yields of organic aerosol particles and emission factors for other atmospheric pollutants were derived for the sources from the spill, recovery, and cleanup efforts. Evaporation and subsequent secondary chemistry produced organic particulate matter with a mass yield of 8 ± 4% of the oil mixture reaching the water surface. Approximately 4% by mass of oil burned on the surface was emitted as soot particles. These yields can be used to estimate the effects on air quality for similar events as well as for this spill at other times without these data. Whereas emission of soot from burning surface oil was large during the episodic burns, the mass flux of secondary organic aerosol to the atmosphere was substantially larger overall. We use a regional air quality model to show that some observed enhancements in organic aerosol concentration along the Gulf Coast were likely due to the DWH spill. In the presence of evaporating hydrocarbons from the oil, NO(x) emissions from the recovery and cleanup operations produced ozone.

Preliminary findings from the Oranga Niho dental student outplacement project.

OBJECTIVES: To examine stakeholder perspectives of the Bachelor of Dental Surgery 2012-2013 clinical outplacement programme with Maori Oral Health Providers (MOHPs) and inform the programme's ongoing development. DESIGN: A mixed methods kaupapa Maori action research project. SETTING: Six North Island MOHPs and the University of Otago Faculty of Dentistry. PARTICIPANTS AND METHODS: Online questionnaires were used to conduct a pre- and post-outplacement survey of dental students and a twice-yearly survey of all MOHP-based clinical supervisors. Paper questionnaires were used to survey adult clients and caregivers of child clients that the students treated. Data were analysed descriptively and thematically. MAIN OUTCOME MEASURES: 68 (61%) of the 112 eligible students completed the pre- and post-outplacement questionnaires; 31 clinical supervisor questionnaire responses were received representing all six MOHPs; and 426 client and 130 caregiver questionnaire responses were received from five MOHPs. RESULTS: 79% of students felt well prepared for outplacement and 75% indicated that they would consider working for a MOHP in future. Of the clinical supervisors, 93% indicated that the students were adequately prepared for outplacement, and 68%, that they would recommend one or more students for employment. However, 58% associated the outplacements with decreased productivity. More than 97% of adult clients and caregivers of child clients were pleased with the care that the students provided. CONCLUSION: Recommendations for strengthening the outplacement programme included: increasing communication between the Faculty, MOHPs and students; addressing the financial cost of the programme to the MOHPs; and providing more support for clinical supervisors.

Forkhead box P3-positive regulatory T-cells and interleukin 17-positive T-helper 17 cells in chronic inflammatory periodontal disease.

BACKGROUND AND OBJECTIVE: The role of two recently identified and closely related T-helper cell subsets - regulatory T-cells [Tregs; forkhead box P3-positive (FOXP3(+) )] and Th17 cells [interleukin-17-positive (IL-17(+) )] - in periodontal disease is yet to be determined. Tregs are essential in maintaining peripheral tolerance and regulating the immune response. Th17 cells play a critical role in several autoimmune diseases, inflammation and host defence. The aim of this study was to determine the presence of FOXP3(+) Tregs and IL-17(+) cells, and their possible spatial interaction, in diseased periodontal tissues. MATERIAL AND METHODS: Twenty-nine archival tissues with nonspecific gingival inflammation were grouped based on the intensity (minimally or intensely inflamed) and nature (T-cell predominant or B- and plasma-cell predominant) of the inflammatory infiltrate. Using double-labelling immunohistochemistry, the concomitant presence of FOXP3(+) and IL-17(+) cells was determined and their spatial relationship was established. In addition, the proportions of FOXP3(+) and IL-17(+) cells were compared between the groups. RESULTS: Of the 29 gingival specimens investigated, 17 were intensely inflamed (≥ 1000 inflammatory cells per 0.12 mm(2) ) and 12 were minimally inflamed (≤ 600 cells per 0.12 mm(2) ). Based on the percentage of CD19(+) B-cells and plasma cells collectively and CD3(+) T-cells, gingival tissues were also grouped into B- and plasma-cell-predominant gingival tissues (n = 21; 50.7% total B- and plasma cells vs. 19.1% T cells; p < 0.001) and T-cell-predominant gingival tissues (n = 8; 61.0% T-cells vs. 15.2% B- and plasma cells; p = 0.007). More FOXP3(+) cells than IL-17(+) cells were observed in all archival gingival tissues examined. A trend towards an increased number of FOXP3(+) cells was observed for intensely inflamed gingival tissues (6.7%) and for B- and plasma-cell-predominant tissues (6.4%) compared with minimally inflamed gingival tissues (4.6%) and T-cell-predominant gingival tissues (4.5%). However, no statistically significant difference in the mean percentage of FOXP3(+) cells between the groups was observed. Interestingly, FOXP3(+) cells were significantly correlated with the B- and plasma-cell/T-cell ratio in B- and plasma-cell-predominant tissues (r = 0.713, p < 0.001). Overall, there were very few IL-17(+) cells (< 1%). All IL-17(+) cells identified in this study had an ovoid/plasmacytoid morphology and were larger in size compared with adjacent inflammatory cells. IL-17(+) and FOXP3(+) cells were not adjacent to each other in any of the areas examined, suggesting that FOXP3(+) Tregs do not directly interact with IL-17(+) cells in diseased gingival tissues. IL-17(+) /FOXP3(+) cells were not detected in the tissues examined. CONCLUSION: These results show that FOXP3(+) cells are more prominent than IL-17(+) cells in periodontal disease processes, which may suggest a predominant role for FOXP3(+) cells in periodontal disease. Further studies are required to characterize these cells more precisely and to understand, in more detail, their roles in the pathophysiology of periodontal disease.

Detection of Candida albicans ADH1 and ADH2 mRNAs in human archival oral biopsy samples.

OBJECTIVES: The aim of this study was to investigate the relationship between expression of Candida albicans alcohol dehydrogenases (ADH) genes in archival formalin-fixed paraffin-embedded (FFPE) samples from biopsies of leukoplakia. MATERIALS AND METHODS: Archival FFPE samples were obtained from four sample groups: normal oral mucosa, non-dysplastic leukoplakia, chronic hyperplastic candidosis (CHC), and non-CHC dysplastic leukoplakia. The presence of C. albicans was determined by periodic acid Schiff staining and by immunocytochemistry. C. albicans ADH1 and ADH2 mRNAs were detected using reverse transcription PCR. RESULTS: Candida albicans was detected in FFPE samples diagnosed as CHC (the histological diagnoses had been made by specialist oral pathologists, using uniform criteria), but not in any other sample group, including the non-dysplastic leukoplakias. RT-PCR confirmed a significant correlation between the expression of CaADH1 mRNA (P = 0.000), but not for CaADH2 mRNA (P = 0.056) in archival FFPE samples (n = 31) from biopsies of leukoplakia. CONCLUSIONS: Candida albicans was the predominant species in the lesions diagnosed as CHC, and the presence of C. albicans in CHC lesions was associated with a high expression of C. albicans ADH1 mRNA. There was no association between the presence of Candida and malignant transformation in the cases examined; however, the number of cases was limited and further studies are needed to further elucidate the role of C. albicans ADH1 in the pathogenesis of oral squamous cell carcinoma.

Domain general frontoparietal regions show modality-dependent coding of auditory and visual rules.

A defining feature of human cognition is our ability to respond flexibly to what we see and hear, changing how we respond depending on our current goals. In fact, we can rapidly associate almost any input stimulus with any arbitrary behavioural response. This remarkable ability is thought to depend on a frontoparietal "multiple demand" circuit which is engaged by many types of cognitive demand and widely referred to as domain general. However, it is not clear how responses to multiple input modalities are structured within this system. Domain generality could be achieved by holding information in an abstract form that generalises over input modality, or in a modality-tagged form, which uses similar resources but produces unique codes to represent the information in each modality. We used a stimulus-response task, with conceptually identical rules in two sensory modalities (visual and auditory), to distinguish between these possibilities. Multivariate decoding of functional magnetic resonance imaging data showed that representations of visual and auditory rules recruited overlapping neural resources but were expressed in modality-tagged non-generalisable neural codes. Our data suggest that this frontoparietal system may draw on the same or similar resources to solve multiple tasks, but does not create modality-general representations of task rules, even when those rules are conceptually identical between domains.

Lung cancer survival in England: trends in non-small-cell lung cancer survival over the duration of the National Lung Cancer Audit.

BACKGROUND: In comparison with other European and North American countries, England has poor survival figures for lung cancer. Our aim was to evaluate the changes in survival since the introduction of the National Lung Cancer Audit (NLCA). METHODS: We used data from the NLCA to identify people with non-small-cell lung cancer (NSCLC) and stratified people according to their performance status (PS) and clinical stage. Using Cox regression, we calculated hazard ratios (HRs) for death according to the year of diagnosis from 2004/2005 to 2010; adjusted for patient features including age, sex and co-morbidity. We also assessed whether any changes in survival were explained by the changes in surgical resection rates or histological subtype. RESULTS: In this cohort of 120,745 patients, the overall median survival did not change; but there was a 1% annual improvement in survival over the study period (adjusted HR 0.99, 95% confidence interval (CI) 0.98-0.99). Survival improvement was only seen in patients with good PS and early stage (adjusted HR 0.97, 95% CI 0.95-0.99) and this was partly accounted for by changes in resection rates. CONCLUSION: Survival has only improved for a limited group of people with NSCLC and increasing surgical resection rates appeared to explain some of this improvement.

RNA processing and the evolution of eukaryotes.

In eukaryotes, RNA processing events, including alternative splicing and RNA editing, can generate many different messages from a single gene. As a consequence, the RNA pool, which we refer to here as the 'ribotype', has a different information content from the genotype and can vary as circumstances change. The outcome of a single RNA processing event often regulates the outcome of another, giving rise to networks that affect the composition and expression of a particular ribotype. Successful ribotypes are determined by natural selection, and can be incorporated into the genome over time by reverse transcription. Eukaryotic evolution is therefore influenced by the alternate ways in which RNAs are processed and the continual interplay between RNA and DNA.

Access to and quality of care for sexual and gender minority women living with HIV in Metro Vancouver, Canada: Results from a longitudinal cohort study.

BACKGROUND: While scarce, literature suggests that women at the intersection of HIV status and gender and/or sexual minority identities experience heightened social and health disparities within health care systems. OBJECTIVES: This study examines the association between sexual and/or gender minority identities and: (1) experiences of poor treatment by health professionals and (2) being unable to access health services among a cohort of women living with HIV in Metro Vancouver, Canada. DESIGN: Data were drawn from a longitudinal community-based cohort of women living with HIV (Sexual Health and HIV/AIDS Women's Longitudinal Needs Assessment). METHODS: We examined associations between sexual and/or gender minority identities and the two outcomes. We drew on explanatory variables to measure sexual minority and gender minority identities independently and a combined variable measuring sexual and/or gender minority identities. The associations between each of these three variables and each outcome were analysed using bivariate and multivariable logistic regression models with generalized estimating equations for repeated measures over time. Adjusted odds ratios and 95% confidence intervals are reported. RESULTS: The study sample included 1460 observations on 315 participants over 4.5 years (September 2014 to February 2019). Overall, 125 (39.7%) reported poor treatment by health professionals and 102 (32.4%) reported being unable to access health care services when needed at least once over the study period. A total of 110 (34.9%) of participants reported sexual and/or gender minority identities, 106 (33.7%) reporting sexual minority identities, with 29 (9.2%) reporting gender minority identities. In multivariable analysis, adjusting for confounders, sexual minority identities, and combined sexual and/or gender minority identities were significantly associated with increased odds of experiencing poor treatment by health professionals (sexual minority adjusted odds ratio = 1.39 (0.94-2.05); sexual and/or gender minority adjusted odds ratio = 1.48 (1.00-2.18)) and being unable to access health services (sexual minority adjusted odds ratio = 1.89 (1.20-2.97); sexual and/or gender minority adjusted odds ratio = 1.91 (1.23-2.98)). In multivariable analysis, gender minority identities were not significantly associated with increased odds of experiencing poor treatment by health professionals (gender minority adjusted odds ratio = 1.38; 95% CI = 0.76-2.52) and being unable to access health services (gender minority adjusted odds ratio = 1.72; 95% CI = 0.89-3.31) possibly due to low sample size among women with gender minority identities. CONCLUSION: Our findings suggest the need for access to inclusive, affirming, trauma-informed health care services tailored specifically for and by women living with HIV with sexual and/or gender minority identities.

Histological evidence of superficial inflammation is associated with lower recurrence of equine sarcoids following surgical removal: A follow-up study of 106 tumours in 64 horses.

Although the equine sarcoid is the most common skin neoplasm in domesticated horses, histopathological characteristics have not previously been evaluated for association with recurrence. The aim of this retrospective cohort study was to investigate clinical and histopathological features of excised equine sarcoids and to evaluate their association with recurrence at the original surgical site and at new sites. Clinical records and excisional biopsies from 106 equine sarcoids from 64 horses referred to Leahurst Equine Hospital, University of Liverpool, between March 2010 and February 2015 were retrieved. Biopsies were re-evaluated histologically. Clinical data were obtained from hospital records, and owner-reported follow-up data were obtained by telephone questionnaire. Associations between clinical and histopathological features of sarcoids and their recurrence at the surgical site were determined using uni- and multivariable mixed effects logistic regression. Recurrence of sarcoids at the surgical site occurred in 30 horses (46.9%). Sarcoids developed at a distant site in 21 horses (32.8%). In the final mixed effects logistic regression model, only superficial inflammation was associated with reduced odds of recurrence at the surgical site (adjusted odds ratio, 0.32; 95% confidence intervals, 0.10-0.96; P = 0.04). This suggests that the inflammatory process may play a role in protecting horses against the recurrence of sarcoids.