Remarks on Legendrian Self-Linking

The Thurston-Bennequin invariant provides one notion of self-linking for any homologically-trivial Legendrian curve in a contact three-manifold. Here we discuss related analytic notions of self-linking for Legendrian knots in Euclidean space. Our definition is based upon a reformulation of the elementary Gauss linking integral and is motivated by ideas from supersymmetric gauge theory. We recover the Thurston-Bennequin invariant as a special case.Comment: 42 pages, many figures; v2: minor revisions, published versio

U-box E3 ubiquitin ligase PUB17 acts in the nucleus to promote specific immune pathways triggered by Phytophthora infestans

Ubiquitination regulates many processes in plants, including immunity. The E3 ubiquitin ligase PUB17 is a positive regulator of programmed cell death (PCD) triggered by resistance proteins CF4/9 in tomato. Its role in immunity to the potato late blight pathogen, Phytophthora infestans, was investigated here. Silencing StPUB17 in potato by RNAi and NbPUB17 in Nicotiana benthamiana by virus-induced gene silencing (VIGS) each enhanced P. infestans leaf colonization. PAMP-triggered immunity (PTI) transcriptional responses activated by flg22, and CF4/Avr4-mediated PCD were attenuated by silencing PUB17. However, silencing PUB17 did not compromise PCD triggered by P. infestans PAMP INF1, or co-expression of R3a/AVR3a, demonstrating that not all PTI- and PCD-associated responses require PUB17. PUB17 localizes to the plant nucleus and especially in the nucleolus. Transient over-expression of a dominant-negative StPUB17V314I,V316I mutant, which retained nucleolar localization, suppressed CF4-mediated cell death and enhanced P. infestans colonization. Exclusion of the StPUB17V314I,V316I mutant from the nucleus abolished its dominant-negative activity, demonstrating that StPUB17 functions in the nucleus. PUB17 is a positive regulator of immunity to late blight that acts in the nucleus to promote specific PTI and PCD pathways

Little groups of irreps of O(3), SO(3), and the infinite axial subgroups

Little groups are enumerated for the irreps and their components in any basis of O(3) and SO(3) up to rank 9, and for all irreps of C$_{\infty}$, C$_{\infty h}$, C$_{\infty v}$, D$_{\infty}$ and D$_{\infty h}$. The results are obtained by a new chain criterion, which distinguishes massive (rotationally inequivalent) irrep basis functions and allows for multiple branching paths, and are verified by inspection. These results are relevant to the determination of the symmetry of a material from its linear and nonlinear optical properties and to the choices of order parameters for symmetry breaking in liquid crystals.Comment: 28 pages and 3 figure

A single genus in the gut microbiome reflects host preference and specificity

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 9 (2015): 90–100, doi:10.1038/ismej.2014.97.Delineating differences in gut microbiomes of human and animal hosts contributes towards understanding human health and enables new strategies for detecting reservoirs of waterborne human pathogens. We focused upon Blautia, a single microbial genus that is important for nutrient assimilation as preliminary work suggested host-related patterns within members of this genus. In our dataset of 57 M sequence reads of the V6 region of the 16S ribosomal RNA gene in samples collected from seven host species, we identified 200 high-resolution taxonomic units within Blautia using oligotyping. Our analysis revealed 13 host-specific oligotypes that occurred exclusively in fecal samples of humans (three oligotypes), swine (six oligotypes), cows (one oligotype), deer (one oligotype), or chickens (two oligotypes). We identified an additional 171 oligotypes that exhibited differential abundance patterns among all the host species. Blautia oligotypes in the human population obtained from sewage and fecal samples displayed remarkable continuity. Oligotypes from only 10 Brazilian human fecal samples collected from individuals in a rural village encompassed 97% of all Blautia oligotypes found in a Brazilian sewage sample from a city of three million people. Further, 75% of the oligotypes in Brazilian human fecal samples matched those in US sewage samples, implying that a universal set of Blautia strains may be shared among culturally and geographically distinct human populations. Such strains can serve as universal markers to assess human fecal contamination in environmental samples. Our results indicate that host-specificity and host-preference patterns of organisms within this genus are driven by host physiology more than dietary habits.This study was funded by the NIH grant R01AI091829-01A1 to SLM

A Study to Validate a Self-Reported Version of the ONS Drug Dependence Questionnaire

Aim: A prospective study to establish the reliability of a self-completion version of the Office for National Statistics (ONS) questionnaire for assessing drug dependence of substance misuse clients. Method: A total of 47 treatment seeking opioid-dependent clients completed the self-complete version of the ONS questionnaire (ONS-sc) followed by the interviewer-administered ONS questionnaire (ONS-ia) at a single clinic appointment. Scores for four Class A drugs (heroin, methadone, speed and crack/cocaine) from both formats were compared. Results: The observed agreement was 87% or more and Cohen's kappa was 0.7 (p < 0.001) or more for all four Class A drugs. Sensitivity for each Class A drugs was 56% or higher and specificity was 87% or higher. Sensitivity for severe heroin dependency was 98% (CI 89–100%). There was a 100% correlation between the ONS-sc and positive urine analysis for heroin use. However, methadone and crack/cocaine drug use appeared under reported. Conclusion: ONS-sc is a feasible, practical and time-saving alternative to a detailed interview on drug dependence. Further research with a larger sample size and non-opiate-dependent clients are needed, as this could prove a useful tool for monitoring clients in everyday practice, or for survey purposes where interviews are impractical

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005–2021)

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required

Systematic review and metaanalysis comparing the bias and accuracy of the modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations in community-based population

BACKGROUND The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1–3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6–3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR

Association between oral health markers and decline in muscle strength and physical performance in later life:longitudinal analyses of two prospective cohorts from the UK and the USA

BACKGROUND: Poor oral health could be associated with changes in musculoskeletal health over time. This aim of this study was to investigate the longitudinal relationship between oral health and decline in physical function in later life. METHODS: We did a prospective analysis of two cohorts of older adults (aged 70 years or older) including men from the British Regional Heart Study (BRHS; n=612), and men and women from the Health, Aging and Body Composition (Health ABC) Study (n=1572), followed up for about 8 years. Data were available for clinical or self-reported oral health measures, muscle (grip) strength, and physical performance (chair stand and gait speed). ANCOVA models were used to assess the association between oral health and follow-up physical function scores. Multivariate logistic regression models were used to examine the associations between oral health and decline in physical function over the follow-up period. In the BRHS, changes in oral health and physical function were also assessed. All models were adjusted for relevant sociodemographic, behavioural, and health-related factors. FINDINGS: In the BRHS, complete tooth loss and difficulty eating were associated with weaker grip strength at follow-up, and periodontal status was associated with decline in gait speed. In the Health ABC Study, complete tooth loss, poor self-rated oral health, and the presence of one oral health problem were associated with slower gait speed at follow-up. In both studies, dry mouth was associated with declines in physical function. In the BRHS, deterioration of dentition (tooth loss) over the follow-up period was associated with decline in chair stand speed (adjusted odds ratio 2·34 [95% CI 1·20-4·46]), as was deterioration in difficulty eating (2·41 [1·04-5·60]). INTERPRETATION: Oral health problems are associated with poorer physical function and greater decline in physical function in older adults, and could be an indicator of individuals at risk of reduced physical capacity and subsequent frailty and disability in later life. FUNDING: The Dunhill Medical Trust and the US National Institutes of Health-National Institute of Dental and Craniofacial Research