False Positive Anti-Topoisomerase I (Scl-70) Antibody Results in Clinical Practice: A Case Series From a Scleroderma Referral Center

PURPOSE: To determine if some patients who tested positive for anti-Scl-70 antibody in clinical practice, but did not have classifiable systemic sclerosis, were negative for anti-Scl-70 antibody by the more specific immunodiffusion method of testing. METHODS: Patients evaluated by a rheumatologist at a Scleroderma referral center who had tested positive for anti-Scl-70 antibody prior to referral, but did not have classifiable SSc based on clinical criteria, were invited to undergo testing for anti-Scl-70 antibody by immunodiffusion. Patient demographics and clinical features were recorded at the time of their evaluation, and diagnostic testing results were reviewed using the medical records. RESULTS: 52 patients were enrolled over an 8-year period, with 48 (92.3%) testing negative and 4 (7.7%) testing positive for anti-Scl-70 antibody by immunodiffusion. Of the 48 patients who tested negative, 18 (37.5%) tested negative for ANA by indirect immunofluorescence, 33 (68.8%) did not have Raynaud\u27s phenomenon, and 43 (89.6%) had ≤1 clinical criteria items based on the 2013 ACR/EULAR SSc classification criteria. Nevertheless, 21 (43.8%) patients who were negative for anti-Scl-70 antibody by immunodiffusion had undergone a chest CT and 14 (29.2%) had undergone an echocardiogram. A total of 23 patients had at least one follow up clinic visit. 3 out of 4 patients who were positive for anti-Scl-70 antibody by immunodiffusion, but none of the 19 patients who tested negative by immunodiffusion, developed sufficient criteria during follow up to be classified as SSc. CONCLUSION: Assays for anti-Scl-70 antibody in commercial laboratories that are commonly utilized in clinical practice can produce false positive results. These results can lead to angst for patients, as well as unnecessary referrals and diagnostic evaluations

Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory conditions. By immunohistochemistry of renal biopsies, patients with focal or crescentic glomerular lesions were found to have the highest expression of calprotectin and those with sclerotic the least. Serum levels of calprotectin as measured by ELISA were elevated in patients with active AAV and the levels decreased but did not normalize during remission, suggesting subclinical inflammation. Calprotectin levels in patients with limited systemic disease increased following treatment withdrawal and were significantly elevated in patients who relapsed compared with those who did not. As assessed by flow cytometry, patients with AAV had higher monocyte and neutrophil cell surface calprotectin expression than healthy controls, but this was not associated with augmented mRNA expression in CD14(+) monocytes or CD16(+) neutrophils. Thus, serum calprotectin is a potential disease biomarker in patients with AAV, and may have a role in disease pathogenesis

Homophily and Contagion Are Generically Confounded in Observational Social Network Studies

We consider processes on social networks that can potentially involve three factors: homophily, or the formation of social ties due to matching individual traits; social contagion, also known as social influence; and the causal effect of an individual's covariates on their behavior or other measurable responses. We show that, generically, all of these are confounded with each other. Distinguishing them from one another requires strong assumptions on the parametrization of the social process or on the adequacy of the covariates used (or both). In particular we demonstrate, with simple examples, that asymmetries in regression coefficients cannot identify causal effects, and that very simple models of imitation (a form of social contagion) can produce substantial correlations between an individual's enduring traits and their choices, even when there is no intrinsic affinity between them. We also suggest some possible constructive responses to these results.Comment: 27 pages, 9 figures. V2: Revised in response to referees. V3: Ditt

Spectrum of non-Hermitian heavy tailed random matrices

Let (X_{jk})_{j,k>=1} be i.i.d. complex random variables such that |X_{jk}| is in the domain of attraction of an alpha-stable law, with 0< alpha <2. Our main result is a heavy tailed counterpart of Girko's circular law. Namely, under some additional smoothness assumptions on the law of X_{jk}, we prove that there exists a deterministic sequence a_n ~ n^{1/alpha} and a probability measure mu_alpha on C depending only on alpha such that with probability one, the empirical distribution of the eigenvalues of the rescaled matrix a_n^{-1} (X_{jk})_{1<=j,k<=n} converges weakly to mu_alpha as n tends to infinity. Our approach combines Aldous & Steele's objective method with Girko's Hermitization using logarithmic potentials. The underlying limiting object is defined on a bipartized version of Aldous' Poisson Weighted Infinite Tree. Recursive relations on the tree provide some properties of mu_alpha. In contrast with the Hermitian case, we find that mu_alpha is not heavy tailed.Comment: Expanded version of a paper published in Communications in Mathematical Physics 307, 513-560 (2011

Evaluation of commercially available RNA amplification kits for RNA sequencing using very low input amounts of total RNA

This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information.Multiple recent publications on RNA sequencing (RNA-seq) have demonstrated the power of next-generation sequencing technologies in whole-transcriptome analysis. Vendor-specific protocols used for RNA library construction often require at least 100 ng total RNA. However, under certain conditions, much less RNA is available for library construction. In these cases, effective transcriptome profiling requires amplification of subnanogram amounts of RNA. Several commercial RNA amplification kits are available for amplification prior to library construction for next-generation sequencing, but these kits have not been comprehensively field evaluated for accuracy and performance of RNA-seq for picogram amounts of RNA. To address this, 4 types of amplification kits were tested with 3 different concentrations, from 5 ng to 50 pg, of a commercially available RNA. Kits were tested at multiple sites to assess reproducibility and ease of use. The human total reference RNA used was spiked with a control pool of RNA molecules in order to further evaluate quantitative recovery of input material. Additional control data sets were generated from libraries constructed following polyA selection or ribosomal depletion using established kits and protocols. cDNA was collected from the different sites, and libraries were synthesized at a single site using established protocols. Sequencing runs were carried out on the Illumina platform. Numerous metrics were compared among the kits and dilutions used. Overall, no single kit appeared to meet all the challenges of small input material. However, it is encouraging that excellent data can be recovered with even the 50 pg input total RNA

The continuum of fetal alcohol spectrum disorders in four rural communities in south africa: Prevalence and characteristics

Prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in previously unstudied rural, agricultural, lower socioeconomic populations in South Africa (ZA)

The continuum of fetal alcohol spectrum disorders in a community in South Africa: Prevalence and characteristics in a fifth sample

The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community

Utilising daily diaries to examine oral health experiences associated with dentine hypersensitivity

Background: The current investigation examined the determinants of oral health experiences associated with dentine hypersensitivity using prospective diary methodology. Methods: Staff and students from a large UK university who had self-diagnosed dentine hypersensitivity completed an online daily diary and text survey for two weeks recording their mood, oral health-related coping behaviours, coping and pain appraisals, pain experiences and functional limitations. Cross sectional and lagged path analyses were employed to examine relationships. Results: 101 participants took part in the diary study. Participants had a mean age of 26.3 years (range=18-63) and most were female (N=69). Individuals who used more oral health-related coping behaviours predicted and experienced greater levels of pain on subsequent days. Negative mood also predicted worse pain outcomes. The daily diary method provided a useful avenue for investigating variations in oral health experiences and relationships between variables that can fluctuate daily. Conclusions: Psychological variables such as coping and mood play an important role in the pain experiences of people with dentine hypersensitivity. The study highlights the benefits of using prospective methods to elucidate the experiences of people with oral condition