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Purpose: The goal of this review article is to reinvigorate interest in lipreading and lipreading training for adults with acquired hearing loss. Most adults benefit from being able to see the talker when speech is degraded; however, the effect size is related to their lipreading ability, which is typically poor in adults who have experienced normal hearing through most of their lives. Lipreading training has been viewed as a possible avenue for rehabilitation of adults with an acquired hearing loss, but most training approaches have not been particularly successful. Here, we describe lipreading and theoretically motivated approaches to its training, as well as examples of successful training paradigms. We discuss some extensions to auditory-only (AO) and audiovisual (AV) speech recognition. Method: Visual speech perception and word recognition are described. Traditional and contemporary views of training and perceptual learning are outlined. We focus on the roles of external and internal feedback and the training task in perceptual learning, and we describe results of lipreading training experiments. Results: Lipreading is commonly characterized as limited to viseme perception. However, evidence demonstrates subvisemic perception of visual phonetic information. Lipreading words also relies on lexical constraints, not unlike auditory spoken word recognition. Lipreading has been shown to be difficult to improve through training, but under specific feedback and task conditions, training can be successful, and learning can generalize to untrained materials, including AV sentence stimuli in noise. The results on lipreading have implications for AO and AV training and for use of acoustically processed speech in face-to-face communication. Conclusion: Given its importance for speech recognition with a hearing loss, we suggest that the research and clinical communities integrate lipreading in their efforts to improve speech recognition in adults with acquired hearing loss.

ObjectiveThe goal of these studies is to discover novel urinary biomarkers of lupus nephritis (LN).MethodsUrine from systemic lupus erythematosus (SLE) patients was interrogated for 1000 proteins using a novel, quantitative planar protein microarray. Hits were validated in an independent SLE cohort with inactive, active non-renal (ANR) and active renal (AR) patients, in a cohort with concurrent renal biopsies, and in a longitudinal cohort. Single-cell renal RNA sequencing data from LN kidneys were examined to deduce the cellular origin of each biomarker.ResultsScreening of 1000 proteins revealed 64 proteins to be significantly elevated in SLE urine, of which 17 were ELISA validated in independent cohorts. Urine Angptl4 (area under the curve (AUC)=0.96), L-selectin (AUC=0.86), TPP1 (AUC=0.84), transforming growth factor-β1 (TGFβ1) (AUC=0.78), thrombospondin-1 (AUC=0.73), FOLR2 (AUC=0.72), platelet-derived growth factor receptor-β (AUC=0.67) and PRX2 (AUC=0.65) distinguished AR from ANR SLE, outperforming anti-dsDNA, C3 and C4, in terms of specificity, sensitivity and positive predictive value. In multivariate regression analysis, urine Angptl4, L-selectin, TPP1 and TGFβ1 were highly associated with disease activity, even after correction for demographic variables. In SLE patients with serial follow-up, urine L-selectin (followed by urine Angptl4 and TGFβ1) were best at tracking concurrent or pending disease flares. Importantly, several proteins elevated in LN urine were also expressed within the kidneys in LN, either within resident renal cells or infiltrating immune cells, based on single-cell RNA sequencing analysis.ConclusionUnbiased planar array screening of 1000 proteins has led to the discovery of urine Angptl4, L-selectin and TGFβ1 as potential biomarker candidates for tracking disease activity in LN.

ObjectiveWe assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19.DesignRandomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory).ResultsOf 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (pConclusionsFamotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required.

Objective: To use factor analysis to structure items from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) into latent variables associated with infectious complications, and then to use structural equation modeling (SEM) to organize those latent variables into a predictive model of POIC. Predictive models of post-operative infectious complications (POIC) have traditionally relied upon logistic regression and inconsistent variable groupings. A more standardized approach to a valid construct would allow for more unitary research and improved clinical decision making. Materials and Methods: The study evaluated data from 1580 recipients of radical cystectomies in the ACS NSQIP PUF 2013 database. Pre-operative, operative, and post-operative data were analyzed. Exploratory Factor Analysis (EFA) and theory-based selection were used to create latent variables for a predictive model of POIC which was analyzed with structural equation modeling.Results: After reducing unrelated variables using EFA, two latent variables successfully predicted POIC, a Global Health Variable (Dyspnea, COPD, Diabetes, and Hypertension) and a Proximal Pre-operative Infectious Comorbidity Variable (pre-operative transfusion, pre-operative wound infection, and pre-operative sepsis). The final model produced was well-fit and suggest two unique pathway indicators for understanding which patients are at higher risk for POIC.Conclusion: Discerning the most significant items and their role in the POIC model offer clinical insight into adverse events and new considerations into the prevention of such events. Patients endorsing multiple items in the model may benefit from pre-operative optimization of modifiable conditions and closer post-operative surveillance.

T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6+ and ALCAM+ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target.

The current under-representation of racial and ethnic minorities and socio-economically disadvantaged participants in clinical trials represents an important problem, because it reduces generalizability of trial results and should urgently be addressed in all diseases. Decentralized trials may improve engagement of under-represented populations with long-standing health disparities and may be relevant to patients with pancreatic cancer who would benefit from at home trial participation. We completed a fully decentralized randomized double-blind phase II clinical trial in New York State for participants with mild-to-moderate COVID-19. Electronic data were collected for 28 days (5 vital readings and 1 survey with 20 questions per day) from 55 non-hospitalized participants. Home monitoring devices, HIPAA compliant data submission technology, and internet access were provided free-of-charge. We enrolled 40% White, 33% Black or African American and 27% Other/Mixed/Unknown participants. Of these, 25% self-identified as Hispanic or Latino. This exceeded national and New York state averages of minority populations, in contrast with the current clinical trial landscape. We found that the local area within a 30-minute return car journey from our main research hospital disproportionately over-represented socio-economically advantaged white inhabitants. We found that decentralization enabled the inclusion of participants living up to a 2-hour journey from this hospital in socio-economically deprived geographies with higher minority race representation. We excluded selection bias, by demonstrating that our trial population represented the differences of social deprivation observed between races at the national and state level (p = 0.003). In addition to trial enrollment, completeness of trial data has an important impact on the veracity of trial results. Half our participants were assigned a dedicated team member to make telephone call reminders if participants had not submitted data by mid-day despite of a pre-ceding automated notification to the supplied electronic device. Daily telephone follow-up significantly reduced missing electronic data in participants living above the median deprivation index (submitted data per day 4 out of 6 vs 6 out of 6: p = 0.03), thereby aiding equitable data collection from traditionally under-represented participant groups. Our findings require further validation and refinement from multiple centers and expansion to patients with reduced mobility and cachexia due to progressing pancreatic cancer. Also, other factors such as language assistance and recruitment methods, need to be addressed in clinical trials to mitigate against their negative impact on equitable recruitment. Nevertheless, for now we identify decentralization combined with engagement telephone calls as readily actionable methods to improve inclusion of under-represented participants in clinical trials. Citation Format: Hassal Lee, Alexander Shakeel Bates, Richard Dima, Sandeep Nadella, Nicole Jordan-Martin, Christina Brennan, Tobias Janowitz. Analysis of methods to improve engagement of under-represented and socioeconomically deprived patients in clinical research [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A050.

Purpose The optimal management of medial humeral epicondyle fractures continues to be debated since decades. This single center study analyzes changes and optimizations of treatment over an observation period of 16 years and reports the results. Materials and Methods Retrospective analysis of all patients treated with a medial humeral epicondyle fracture between 2005 and 2020 at our institution. Results Ninety-six patients (mean 9.3 years, range 1 - 15) were included in the study. In 25 cases (26 %), the fracture was associated with an elbow dislocation. Most patients received surgical treatment (83.3 %), whereas 17.7 % were treated nonoperatively. Surgical treatment consisted of open reduction and fixation with compression screw (n = 44 steel, n = 2 absorbable), K-wire (n = 30), a combination of screw/K-wire (n = 2), or a PDS suture (n = 1). Compression screws have been used significantly more often in the latter half of the study period (p = 0.006). Patients were immobilized in a long arm cast for 29 days (range 11 – 50). Eleven surgically treated patients were early mobilized in an elbow orthosis. After a mean follow up of 7.6 months [ 2 – 61), Mayo elbow performance index (MEPI) outcome was excellent in all 96 patients. Loss of elbow movement (LOM) was found to be mild in 30 and moderate in 15 patients. LOM was found to be associated with surgical treatment (p = 0.001), and with concomitant elbow dislocations (p = 0.29). One pseudarthrosis occurred after conservative treatment. A persistence of ulnar nerve palsy or recurrent joint instability has not been described. Conclusion Most children with medial humeral epicondyle fractures nowadays undergo surgery. Screw osteosynthesis represents the increasingly preferred method in order to prevent joint instability or non-union, and to allow shorter immobilization duration. Overall results after medial epicondyle fractures are good.

Background Classification and treatment decisions in lupus nephritis (LN) are largely based on renal histology. Single-cell RNA sequencing (scRNAseq) analysis may accurately differentiate types of renal involvement at the transcriptomic level, and better inform treatment decisions and prognosis. Methods scRNAseq was performed on kidney and non-lesional skin tissue collected from 20 SLE patients undergoing a clinically indicated renal biopsy. Cell types were determined using principal component analysis and t-distributed stochastic neighbor embedding (tSNE) plotting, resulting in the definitive identification of keratinocytes, tubular cells, mesangial cells, fibroblasts, endothelial cells, and leukocytes. Results LN patients expressed upregulated IFN response genes in both their tubular cells and keratinocytes. This IFN response signature in tubular cells predicted poor response to therapy 6 months post-biopsy. Tubular cells of non-responder patients also expressed upregulated extracellular matrix proteins and fibrotic markers (figure 1A and 1B). Using logistic regression analysis, a 4-gene tubular fibrosis score was created and able to predict response to treatment with an area under curve of 0.9 (figure 1C). Keratinocytes of non-responders also upregulated certain extracellular matrix genes and this response was not observed in peripheral blood mononuclear cells. Differential expression analysis between histology classes indicated an upregulation of IFN and TNF signaling in the tubular cells of patients with proliferative LN compared with membranous. Conclusions scRNAseq from 2–10 mm of renal biopsy tissue in SLE can differentiate between the different classes of LN, and provide important insights into potential pathogenic mechanisms. Further, changes in the skin of LN patients can provide a useful source of biomarkers and may reflect important information concerning concurrent kidney pathological events. Funding Source(s): This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network. AMP is a public-private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb, Foundation for the National Institutes of Health, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals) created to develop new ways of identifying and validating promising biological targets for diagnostics and drug development. Funding was provided through grants from the National Institutes of Health (UH2-AR067676, UH2-AR067677, UH2-AR067679, UH2-AR067681, UH2-AR067685, UH2-AR067688, UH2-AR067689, UH2-AR067690, UH2-AR067691, UH2-AR067694, and UM2-AR067678).

In the presented study the response of a carbon-glass composite/steel/(elastomer) multi-material structure to low-velocity impact was investigated experimentally. Two different steel layer thicknesses, 0.125 mm and 0.25 mm, as well as the addition of a rubber layer were assessed regarding their influence on internal and external damage, the absorbed energy, force evolution, and deformation. It was found that the doubling of the steel layer thickness stiffens the structure marginally and induces deeper indentations but has no significant influence on the absorbed energy or the damage threshold F D . The additional rubber layer increases the damage threshold load. Below this threshold, the response is dominated by global, elastic deformation decreasing internal and external damage and thereby the amount of absorbed energy. Above F D , large local deformations around the centre of impact lead to a more critical surface damage which dissipate a part of the energy decreasing the extend of delaminations.

Our recent study has implicated bradykinin (BK) signaling as being of pathogenic importance in lupus. This study aims to investigate the biomarker potential of BK peptides, BK and BK-des-arg-9, in lupus and other rheumatic autoimmune diseases. Sera from systemic lupus erythematosus (SLE) patients and healthy subjects were screened for BK and BK-des-arg-9 by liquid chromatography–mass spectrometry metabolomics. Serum from 6-mo-old C57BL/6 mice and three murine lupus strains were also screened for the two peptides by metabolomics. Given the promising initial screening results, validation of these two peptides was next conducted using multiple reaction monitoring in larger patient cohorts. In initial metabolomics screening, BK-des-arg-9 was 22-fold higher in SLE serum and 106-fold higher in mouse lupus serum compared with healthy controls. In validation assays using multiple reaction monitoring and quadrupole time-of-flight mass spectrometry, BK and BK-des-arg-9 showed significant elevations in SLE serum compared with controls (p < 0.0001; area under the curve = 0.79–0.88), with a similar but less pronounced increase being noted in rheumatoid arthritis serum. Interestingly, increased renal SLE disease activity index in lupus patients was associated with reduced circulating BK-des-arg-9, and the reasons for this remain to be explored. To sum, increased conversion of BK to the proinflammatory metabolite BK-des-arg-9 appears to be a common theme in systemic rheumatic diseases. Besides serving as an early marker for systemic autoimmunity, independent studies also show that this metabolic axis may also be a pathogenic driver and therapeutic target in lupus.

Legislative bodies have very important roles and understanding the psychology of their decision-making processes is a useful area of study. We add to this area by replicating two previous studies Abe (2012) and Matsumoto, and Hwang (2013) in the context of a legislative body. The present study hypothesized that legislators who support war measures be externally focused and less cognitively complex in their speeches while opponents of war measures would be internally focused. Speeches were obtained pertaining to the decisions for the U.S. to take military action in Kosovo, Iraq, and Libya. While we found mixed results depending on the circumstances of a specific conflict, we demonstrate how automated language analysis can be combined with voting records to better understand behavioral action, such as legislative decision.

Lupus nephritis is a leading cause of mortality among systemic lupus erythematosus (SLE) patients, and its heterogeneous nature poses a significant challenge to the development of effective diagnostics and treatments. Single cell RNA sequencing (scRNA-seq) offers a potential solution to dissect the heterogeneity of the disease and enables the study of similar cell types distant from the site of renal injury to identify novel biomarkers. We applied scRNA-seq to human renal and skin biopsy tissues and demonstrated that scRNA-seq can be performed on samples obtained during routine care. Chronicity index, IgG deposition, and quantity of proteinuria correlated with a transcriptomic-based score composed of IFN-inducible genes in renal tubular cells. Furthermore, analysis of cumulative expression profiles of single cell keratinocytes dissociated from nonlesional, non–sun-exposed skin of patients with lupus nephritis also revealed upregulation of IFN-inducible genes compared with keratinocytes isolated from healthy controls. This indicates the possible use of scRNA-seq analysis of skin biopsies as a biomarker of renal disease. These data support the potential utility of scRNA-seq to provide new insights into the pathogenesis of lupus nephritis and pave the way for exploiting a readily accessible tissue to reflect injury in the kidney.

Objective We compared the prevalence and the clustering of the metabolic syndrome (MetS) components (obese body mass index [BMI; ≥30 kg/m2], hypertriglyceridemia, low high-density lipids, hypertension, and diabetes mellitus) in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. Methods We included CORRONA participants with a rheumatologist-confirmed clinical diagnosis of PsA or RA with complete data. We used a modified definition of MetS that did not include insulin resistance, waist circumference, or blood pressure measurements. Logistic regression models were adjusted for age, sex, and race. Results In the overall CORRONA population, the rates of diabetes mellitus and obesity were significantly higher in PsA compared with RA. In 294 PsA and 1,162 RA participants who had lipids measured, the overall prevalence of MetS in PsA versus RA was 27% versus 19%. The odds ratio (OR) of MetS in PsA versus RA was 1.44 (95% confidence interval [95% CI] 1.05–1.96, P = 0.02). The prevalence of hypertriglyceridemia was higher in PsA compared with RA (38% versus 28%; OR 1.51 [95% CI 1.15–1.98], P = 0.003). The prevalence of type 2 diabetes mellitus was also higher in PsA compared with RA (15% versus 11%; OR 1.56 [95% CI 1.07–2.28], P = 0.02) in the adjusted model. Similarly, higher rates of hypertriglyceridemia and diabetes mellitus were observed in the subgroup of PsA and RA patients with obese BMI. Conclusion Compared with RA, PsA is associated with higher rates of obesity, diabetes mellitus, and hypertriglyceridemia.

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.

Classification and treatment decisions in lupus nephritis (LN) are largely based on renal histology. Single-cell RNAseq (scRNAseq) analysis may accurately differentiate types of renal involvement at the transcriptomic level, and better inform treatment decisions and prognosis. scRNAseq was performed on kidney and non-lesional skin tissue collected from clinically indicated renal biopsies, and skin biopsies obtained at the time of renal biopsies, in 20 systemic lupus erythematosus (SLE) patients. Cell-types were determined using principal component analysis and tSNE plotting, resulting in the definitive identification of keratinocytes, tubular cells, mesangial cells, fibroblasts, endothelial cells, and leukocytes. Tubular cells in patients with proliferative nephritis demonstrated upregulated TNF signaling compared with membranous nephritis. Interestingly, keratinocytes of patients with proliferative nephritis also demonstrated upregulated TNF signaling. Furthermore, tubular cells of patients who did not respond to standard immunosuppressive treatment showed upregulation of extracellular matrix proteins and fibrotic markers at the time of biopsy. Using logistic regression analysis, a 4-gene tubular fibrosis score was created which predicted response to treatment, with an area under curve of 0.9. We conclude that scRNAseq using small amounts of renal biopsy tissue in SLE can differentiate between the different classes of LN, and provide important insights into potential pathogenic mechanisms. Further, changes in the skin of LN patients can provide a useful source of biomarkers and may reflect important information concerning concurrent kidney pathological events.

To study the effects of hydrogen peroxide exposure on mitochondrial DNA (mtDNA) in cultured human corneal epithelial cells. In addition, we compared the integrity of mtDNA found in epithelial cells isolated from keratoconus (KC) and normal (NL) corneas.Telomerase immortalized human corneal epithelial cell line (hTCEpi) were cultured at pH 7.0 or pH 5.0 with or without 200 microM hydrogen peroxide (H2O2). Immunohistochemistry with a marker for oxidative damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), was performed on KC and NL corneas (n = 10). Epithelial cells were isolated from KC corneas (n = 5) and NL corneas (n = 7). Total DNA was extracted, and the mtDNA was analyzed by long extension polymerase chain reaction (LX-PCR). The ratios of mtDNA to nuclear DNA were measured by PCR. The mtDNA control regions were PCR amplified and sequenced.In the epithelial cell cultures, the full-length LX-PCR mtDNA decreased 54% and 44% in the H2O2 + pH7 cultures and H2O2 + pH5 cultures, respectively. 8-OH-dG was present in all layers of KC epithelial cells but only in superficial layers of NL epithelial cells. The isolated KC and NL epithelial cells had comparable levels of full-length LX-PCR mtDNA (16.2 kb) and smaller sized mtDNA bands (4.3 +/- 0.99 vs 4.0 +/- 0.83 bands per individual, respectively). There were no significant differences in the control region nucleotide sequences in KC and NL epithelia.Hydrogen peroxide can significantly degrade LX-PCR mtDNA in vitro. Although the KC epithelium showed a higher degree of oxidative damage, the levels of mtDNA damage in NL and KC epithelial cells were similar to each other.

The microstructure and the mechanical properties of spray deposited materials depend critically on the conditions that are present during deposition and may be modified through changes of the processing parameters. Within the scope of the special research program at the University of Bremen, investigations of the influences of various process and production related parameters on the spray deposition behaviour and the resulting material properties of copper based materials have performed. In order to achieve a fundamental analysis, the investigations were at first focused on pure copper to eliminate influences of alloying elements. Based on these results, investigations of several copper alloys, especially Cu–Sn, Cu–Ni and Cu–Cr with different compositions have been started. The present paper gives an overview of the microstructure development of sprayed pure copper and selected copper alloys in dependence on the process parameters and the process technology supplemented by results of numerical process simulation.

Objectives: To investigate the factors associated with medication compliance in a multi-ethnic population of patients with systemic lupus erythematosus in an urban community.Methods: We surveyed patients in our cohort using the standardized measures of the Compliance- Questionnaire-Rheumatology (CQR), the Beliefs about Medications Questionnaire (BMQ), as well as patient selfreported compliance. Demographic and clinical characteristics of compliant and non-compliant patients underwent bivariate analysis. A multivariate analysis was then performed on variables of interest.Results: Of the 94 patients who agreed to participate in the survey, 89 fully completed each questionnaire. Overall, 48% of patients were compliant by CQR. In multivariate analyses, higher education level was associated with non-compliance. Spanish-speaking patients and those with an income of greater than $15,000 per year were more likely to be compliant.Conclusions: In this urban lupus population, several factors may influence medication compliance. Factors associated with non-compliance are not what have been found in other populations. Further studies looking into specific reasons for certain areas of non-compliance as well as addressing these issues will be important in both treatment and outcomes in lupus patients in implementing appropriate interventions.

OBJECTIVE: Given the social constraints imposed by a gluten-free diet, it can be hypothesized that children with celiac disease (CD) living in the United States have a reduced health-related quality of life (HRQOL); however, there is no validated CD-specific HRQOL instrument for children living in the United States. The goals of this study were to develop and validate a CD-specific HRQOL instrument for children 8 to 18 years of age with CD and to report HRQOL in these children using both generic- and disease-specific instruments. METHODS: This was a prospective study using focus group methodology to develop a CD-specific HRQOL instrument that was then administered to children 8 to 18 years of age with CD living throughout the United States. Instrument validation methods included construct, convergent, and divergent validities. RESULTS: Two instruments were developed: CD-specific pediatric HRQOL instrument (CDPQOL) 8 to 12 and CDPQOL 13 to 18. A total of 181 children with CD completed the CDPQOL as well as a comparator generic instrument. Exploratory factor analysis restructured the CDPQOL and reduced the total number of items. The CDPQOL showed a moderate agreement with the Psychosocial dimensions of the generic instrument confirming convergent validity and low-to-moderate agreement with the Physical Health Summary dimension of the generic instrument confirming divergent validity. CONCLUSIONS: The CDPQOL, consisting of 13 to 17 questions, is a validated instrument for the measurement of HRQOL in children 8 to 18 years of age with CD living in the United States.

We compared the prevalence and the clustering of the metabolic syndrome (MetS) components (obese body mass index [BMI; ≥30 kg/m(2) ], hypertriglyceridemia, low high-density lipids, hypertension, and diabetes mellitus) in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry.We included CORRONA participants with a rheumatologist-confirmed clinical diagnosis of PsA or RA with complete data. We used a modified definition of MetS that did not include insulin resistance, waist circumference, or blood pressure measurements. Logistic regression models were adjusted for age, sex, and race.In the overall CORRONA population, the rates of diabetes mellitus and obesity were significantly higher in PsA compared with RA. In 294 PsA and 1,162 RA participants who had lipids measured, the overall prevalence of MetS in PsA versus RA was 27% versus 19%. The odds ratio (OR) of MetS in PsA versus RA was 1.44 (95% confidence interval [95% CI] 1.05-1.96, P = 0.02). The prevalence of hypertriglyceridemia was higher in PsA compared with RA (38% versus 28%; OR 1.51 [95% CI 1.15-1.98], P = 0.003). The prevalence of type 2 diabetes mellitus was also higher in PsA compared with RA (15% versus 11%; OR 1.56 [95% CI 1.07-2.28], P = 0.02) in the adjusted model. Similarly, higher rates of hypertriglyceridemia and diabetes mellitus were observed in the subgroup of PsA and RA patients with obese BMI.Compared with RA, PsA is associated with higher rates of obesity, diabetes mellitus, and hypertriglyceridemia.

The reinforcing and subjective effects of brief (about 1.5 min) exposures to nitrous oxide, ranging from inspired concentrations of 20–80% in oxygen, were examined in 11 healthy volunteers. A choice procedure was used in which during each of four sessions, subjects first sampled a given concentration of nitrous oxide and placebo oxygen, and then chose between the two. 20, 40, 60 and 80% nitrous oxide were chosen by five, four, three, and three subjects, respectively—these choice levels did not exceed that of chance. All concentrations had psychoactive effects, and in general, concentration-related subjective effects were found. We conclude that in a medical setting, nitrous oxide inhaled in a manner similar to that when used recreationally in a naturalistic setting, does not function as a reinforcer across a wide range of concentrations, in subjects with a modest lifetime history of psychoactive drug use.

The four members of the epidermal growth factor receptor (EGFR/ERBB) family form homo- and heterodimers which mediate ligand-specific regulation of many key cellular processes in normal and cancer tissues. While signaling through the EGFR has been extensively studied on the molecular level, signal transduction through ERBB3/ERBB4 heterodimers is less well understood. Here, we generated isogenic mouse Ba/F3 cells that express full-length and functional membrane-integrated ERBB3 and ERBB4 or ERBB4 alone, to serve as a defined cellular model for biological and phosphoproteomics analysis of ERBB3/ERBB4 signaling. ERBB3 co-expression significantly enhanced Ba/F3 cell proliferation upon neuregulin-1 (NRG1) treatment. For comprehensive signaling studies we performed quantitative mass spectrometry (MS) experiments to compare the basal ERBB3/ERBB4 cell phosphoproteome to NRG1 treatment of ERBB3/ERBB4 and ERBB4 cells. We employed a workflow comprising differential isotope labeling with mTRAQ reagents followed by chromatographic peptide separation and final phosphopeptide enrichment prior to MS analysis. Overall, we identified 9686 phosphorylation sites which could be confidently localized to specific residues. Statistical analysis of three replicate experiments revealed 492 phosphorylation sites which were significantly changed in NRG1-treated ERBB3/ERBB4 cells. Bioinformatics data analysis recapitulated regulation of mitogen-activated protein kinase and Akt pathways, but also indicated signaling links to cytoskeletal functions and nuclear biology. Comparative assessment of NRG1-stimulated ERBB4 Ba/F3 cells revealed that ERBB3 did not trigger defined signaling pathways but more broadly enhanced phosphoproteome regulation in cells expressing both receptors. In conclusion, our data provide the first global picture of ERBB3/ERBB4 signaling and provide numerous potential starting points for further mechanistic studies. ispartof: PLOS ONE vol:11 issue:1 ispartof: location:United States status: published

(1991). Maurice Gamelin, Italy and the eastern alliances. Journal of Strategic Studies: Vol. 14, No. 4, pp. 428-441.

This chapter investigates a very specific kind of culture: that of the extensive private music teaching and learning practice carried out throughout much of the Western world and present in slightly different forms in other cultural traditions like Indian classical music. “Private teaching, private learning” is conceptually, at least, part of a rather loosely defined yet powerful “institution”, and as such it is an intriguing form of teaching and learning: it is ubiquitous, and it is close to people’s everyday living experience, since teacher and learner may exist in a one-on-one context within a domestic setting. This kind of institution interconnects with more formal or typically recognized institutions of the junior and senior academy/conservatory, also present the world over, in different guises. At the senior level, these institutions are often equivalents to universities, and are bastions of excellence in musical performance. They have their own curricula, examination systems and awards, often regulated by national bodies, and many are internationally recognized: the Julliard School of Music, New York; the Royal College of Music, London; the Mozarteum, Saltzburg, for example.At the more junior levels, even in the private home-based scenario, there is also some sort of curriculum. This can be a formal and nationally recognized qualification, such as theory and practical examination boards present in many countries that offer levels of achievement up to universitylevel entrance. But the curriculum might simply be a negotiated contract between teacher and student – for example, to play so many scales and pieces by a specific deadline, or to participate in a concert at the teacher’s home. The place of “private teaching, private learning” as institution presented here is an attempt to bring insight into how and why this form of education is so common and why it should be better understood. The chapter traces a learning pathway typical for manyWestern classical music students who progress from home-based to senior conservatory music learning. It investigates the pros and cons of how teaching and learning is approached in these contexts. Research on

PURPOSE To determine whether keratoconus (KC) corneas have more mitochondrial (mt)DNA damage than do normal corneas. METHODS Thirty-three normal corneas and 34 KC corneas were studied. Immunohistochemistry for mitochondria-encoded cytochrome c oxidase (complex IV) subunit 1 (CO-Iota) and porins was performed. Total DNA was isolated and mtDNA genome amplified by either long-extension-polymerase chain reaction (LX-PCR) or short-extension-PCR (SX-PCR). LX-PCR mtDNA was digested with restriction enzymes to confirm full-length mtDNA amplicon. SX-PCR mtDNA was probed by Southern blot analysis. The T414G mutation was analyzed by peptide nucleic acid directed clamping PCR. Real-time PCR measured the ratio of mtDNA to nuclear (n)DNA. RESULTS KC corneas had decreased CO-Iota in areas of corneal thinning. LX-PCR mtDNA digested with restriction enzymes showed expected size bands except for PstI, which showed two additional bands in some KC corneas (2/18). By both LX-PCR (7.4 +/- 3.8 vs. 4.3 +/- 2.7, P < 0.04) and SX-PCR (5.5 +/- 0.55 vs. 2.4 +/- 2.0, P < 0.006), KC corneas had an increased number of smaller-sized bands (representing mtDNA deletions/mutations) compared with normal corneas. Southern blot analysis of SX-PCR products confirmed their mtDNA origin. The T414G mutation was not detected in either KC or normal corneas. KC corneas showed a trend of lower mtDNA-to-nDNA ratio (26%, P < 0.7) than did normal corneas. CONCLUSIONS KC corneas exhibit more mtDNA damage than do normal corneas. The previously reported increased oxidative stress and altered integrity of mtDNA may be related to each other and may be important in KC pathogenesis.

Objectives: To examine the relationship between postmodern values, demographic variables and people’s attitudes towards and use of acupuncture, aromatherapy and naturopathy. Design: One hundred and seventy-one adults completed a survey measuring postmodern values about health, attitudes towards and use of complementary and alternative medicine (CAM), age, gender, education, and current and recent health. Setting: Griffith University, Gold Coast, Australia. Main outcome measures: Attitudes to CAM and use of CAM. Results: Postmodern values significantly predicted attitudes to CAM and actual use of CAM. Age also significantly predicted attitudes to CAM. Conclusions: The results highlight the importance of patients’ belief in natural remedies and in their active involvement in the healing process.

Objective: To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE). Methods: The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a nonserological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity. Results: AUC for EC4d (0.82±0.02) and BC4d (0.84 ±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p

To describe three patients with congenital glaucoma homozygous and compound heterozygous for different mutations and benign sequence variants in the cytochrome P 450 1B1 (CYP1B1) gene.All patients were examined by slit-lamp biomicroscopy, gonioscopy, measurement of the cornea and optic disc, ultrasound biometry, and automated static threshold perimetry when possible. Direct sequence analysis was performed on DNA extracted from peripheral blood from the patients and their parents.For patient 1, a newborn boy with buphthalmos and an opaque cornea, a novel homozygous C/T transition in codon 355 (CGATGA) led to a predicted nonsense codon Arg355X truncating the protein by 188 amino acids. For patient 2, a 24-year-old man, a compound heterozygous mutation 1410-1422del/1546-1555dup was found. For patient 3, a 34-year-old man, two novel heterozygous missense mutations resulting in an Ala443Gly and a Glu229Lys amino acid exchange and five benign sequence variants were found.Our results confirm the crucial role of CYP1B1 mutations for congenital glaucoma.

Background Psoriatic arthritis (PsA) is associated with a higher frequency of abnormal lipids and obesity compared with healthy controls and rheumatoid arthritis. There is also an increased risk of developing PsA in obese individuals, perhaps related to the inflammatory milieu provided by excess adiposity. It is also known that inflammatory cytokines contribute to derangements in lipid metabolism. However, the relationship between disease activity and lipid profiles in PsA is not well studied. Objectives To assess the cross-sectional relationship between PsA disease activity and lipid profiles in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. Methods We analyzed PsA patients followed in CORRONA between 6/2008 and 10/2012 with complete data for lipids and disease activity. Moderate to high disease activity was defined as CDAI>10 and/or presence of enthesitis/dactylitis. Abnormal lipids were defined as: total cholesterol (TC)>200 mg/dl (5.17 mmol/L), High Density Lipoprotein (HDL) 100 mg/dl (2.59 mmol/L), Triglycerides (TG)>150 mg/dl (1.7 mmol/L), and atherogenic ratio (TC/HDL) >5. Models were adjusted for gender, duration of PsA, mHAQ, disease-related medication use, smoking, body mass index (BMI), diabetes (DM), use of cholesterol medications and fish oil. Results Of the 725 PsA patients included in this study, 284 (39%) had moderate to high disease activity. Compared to the low disease activity group, the moderate to high disease activity group had a higher proportion of women (57% vs 46%, p=0.006) and smokers (12.7% vs 7.7%, p=0.029), higher log ESR (2.44 vs 2.13, p=0.003) and log CRP (1.63 vs 1.31, p=0.002), and shorter disease duration (mean 8.7 vs 11.2 years, p=0.001). Those with moderate to high disease activity were more likely to be prescribed prednisone (13% vs 4.5%, p Moderate to high disease activity was associated with higher odds of TC>200 mg/dl, OR 1.6 (1.1, 2.2 95%CI), p=0.010, and higher odds of TG>150 mg/dl, OR 1.6 (1.2, 2.3 95% CI), p=0.005. Enthesitis/dactylitis was positively associated with TC>200 mg/dl, OR 1.6 (1.1, 2.5), p=0.02. There was no significant association found between disease activity and other lipid measures in the moderate to high disease vs low disease groups. Conclusions Moderate to high disease activity in PsA is associated with increased levels of total cholesterol and triglycerides, suggesting a commonality between PsA disease mechanisms and lipid metabolism that deserves further exploration. The implications of this association for cardiovascular disease in PsA need to be studied further. Disclosure of Interest None Declared

SLE is a chronic, recurrent, potentially fatal multisystem inflammatory disorder mainly affecting women. SLE patients produce antibodies to many different self-antigens. Yet, currently used serological markers for SLE are lacking in specificity and/or sensitivity. The aim of this study was to develop an improved diagnostic test by measuring and multiplexing specific autoantibody reactivities in SLE patients. Autoantibody reactivity profiles in serum samples collected from 97 SLE patients within three years of the diagnosis were compared with those of 56 healthy controls. Autoantibody profiles were determined using the ImmunArray iCHIP™ - a proprietary protein microarray technology that allows the display of antigens representing a wide range of SLE-associated biochemical pathways on a single chip. Using this novel platform, SLE patients could be differentiated from healthy subjects by a relatively small subset of auto-antigens and Epstein Barr Virus (EBV) antigens. The autoantibody reactivity profile that allowed SLE diagnosis with high sensitivity and specificity displayed differential response to known SLE-specific antigens, such as single-stranded DNA and EBV, and to several novel ones. Conclusion: An antibody profile for SLE diagnosis using a single multiplexed chip was successfully developed. This profile may differentiate between SLE patients and healthy individuals. Validation of this profile in additional patient samples is ongoing.

PURPOSE To determine whether keratoconus (KC) corneal fibroblast cultures have increased reactive oxygen species (ROS) production and are more susceptible to stress-related challenges. METHODS Normal (n = 9) and KC (n = 10) stromal fibroblast cultures were incubated in either neutral- or low-pH conditions, with or without hydrogen peroxide. Catalase activities were measured with a fluorescent substrate assay. Superoxide and ROS/reactive nitrogen species (RNS) productions were determined with an amine-reactive green-dye assay and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) dye assay, respectively. Cell viability was analyzed by a dye-exclusion assay. Caspase 3 activity was measured by a fluorochrome inhibitor of caspase (FLICA) assay. A cationic (green) dye was used to measure the mitochondrial membrane potential (delta psi m). RESULTS KC fibroblasts had increased superoxide and ROS/RNS production (6.2-fold, P < 0.001 and 1.8-fold, P < 0.001, respectively) and catalase activity (P < 0.01) with higher concentrations of H2O2 compared with normal cultures (P = 0.16). After a low-pH stress challenge, KC fibroblasts maintained higher ROS/RNS levels (3.3-fold, P < 0.02), showed higher caspase-3 activity (7.5-fold, P < 0.02) and decreased delta psi m (2.6-fold, P < 0.04), and had decreased cell viability (37%, P < 0.005 vs. 20%, P < 0.27) compared with normal fibroblasts. CONCLUSIONS Under identical conditions, KC fibroblasts had increased basal generation of ROS/RNS and were more susceptible to stressful challenges (low-pH and/or H2O2 conditions) than were normal fibroblasts. In addition, the stressed KC fibroblasts possessed characteristics similar to those found in the intact KC corneas (increased catalase activity, ROS production, and apoptosis). These properties may play a role in the pathogenesis of KC.

The potential of using fast atom bombardment mass spectrometry for the detection and the characterization of digoxin and a series of related cardenolide analogues was investigated. The spectra were dependent upon the type of support-matrix in which they were recorded; thioglycerol proved to be satisfactory for the characterization of digoxin and allowed for its detection in human urine extract spiked with ca 11 ng ml−1.

Riegelman and Collier have recently reviewed (1) the application of first moment analysis, also termed the mean residence time (MRT) method, to the evaluation ofin vivo absorption time using plasma concentration data following single dose administration. The object of the present report is to apply the MRT method, as well as conventional pharmacokinetic techniques, and to evaluate data derived from comparative bioavailability trials of controlled release formulations versus conventional products. The analyses were performed on data from single dose as well as from multiple dose studies conducted in our laboratories.