An evaluation of the Amblyopia and Strabismus Questionnaire using Rasch analysis

noPURPOSE. To evaluate whether the Amblyopia and Strabismus Questionnaire (A&SQ) is a suitable instrument for the assessment of vision-related quality-of life (VR-QoL) in individuals with strabismus and/or amblyopia. METHODS. The A&SQ was completed by 102 individuals, all of whom had amblyopia, strabismus, or both. Rasch analysis was used to evaluate the usefulness of individual questionnaire items (i.e., questions); the response-scale performance; how well the items targeted VR-QoL; whether individual items showed response bias, depending on factors such as whether strabismus was present; and dimensionality. RESULTS. Items relating to concerns about the appearance of the eyes were applicable only to those with strabismus, and many items showed large ceiling effects. The response scale showed disordered responses and underused response options, which improved after the number of response options was reduced from five to three. This change improved the discriminative ability of the questionnaire (person separation index increased from 1.98 to 2.11). Significant bias was found between strabismic and nonstrabismic respondents. Separate Rasch analyses conducted for subjects with and without strabismus indicated that all A&SQ items seemed appropriate for individuals with strabismus (Rasch infit values between 0.60 and 1.40), but several items fitted the model poorly in amblyopes without strabismus. The AS&Q was not found to be unidimensional. CONCLUSIONS. The findings highlight the limitations of the A&SQ instrument in the assessment of VR-QoL in subjects with strabismus and especially in those with amblyopia alone. The results suggest that separate instruments are needed to quantify VR-QoL in amblyopes with and without strabismus

When Do Single Mothers Work? An Analysis of the 1990 Census Data

This study analyzes the relative effect of the amount of public assistance income received one year on the probability that a single mother is employed the following year compared to a variety of other determinants of employment status. The analysis is based on a national sample which was drawn from the Public Use Micro data 5 percent Sample (PUMS) of the 1990 U.S. Census. It consists of the 275,744female householders who were divorced, separated, widowed or never married, and living with their own children age 18 and under. Logistic regression was utilized to calculate the probability of being employed in 1990 according to sources and amounts of income in 1989, level of education, age, work experience, number and age of children, race, and marital status. The results indicate that greater amounts of public assistance income reduced the probability of being employed. However, several other factors-including race-ethnicity, family form and size, educational background and previous earnings-were significant, independent determinants of labor-force status. In particular, African- American women, women with children under six, women with relatively low levels of education and low earnings in the previous year, and nevermarried women all faced a reduced probability of being employed in 1990 regardless of how much public assistance income they received in 1989. The paper concludes with an assessment of the implications of these findings for current debates on the relationships among welfare receipt, work incentives, and employment

Mesoscopic modelling of enamel interaction with mid-infrared sub-ablative laser pulses

Using a finite element approach the authors model the influence of enamel's microstructure and water distribution on the temperature and stress at the centre of the laser spot, for a CO2 laser working at 10.6 μm, with 0.35 μs pulse duration and sub-ablative intensity. The authors found that the distribution of water in enamel significantly influences the stress generated at the end of one laser pulse: much lower (two orders of magnitude) stress values occur in models with homogeneously distributed water than in models with 0.27 vol.% water located in pores or 4 vol.% in layers. The amount of water in enamel has a strong influence on the stress distribution, but not on the maximum stress values reached. However, different water contents do not influence the temperature distribution in enamel. These results suggest that adequate modelling of the ablation mechanisms in enamel, as in other highly inhomogeneous materials, must include their structure at the mesoscopic scale

Bunyamwera orthobunyavirus glycoprotein precursor is processed by cellular signal peptidase and signal peptide peptidase

This study was supported by Wellcome Trust Grant 099220/B/12/Z (to R.M.E.) and Grant 094476/Z/10/Z that funded the purchase of the TripleTOF 5600 mass spectrometer at the Biomedical Sciences Research Complex (BSRC) of University of St. Andrews.Bunyamwera virus (BUNV) is the prototype of the Orthobunyavirus genus and Bunyaviridae family that contains important human and animal pathogens. The cleavage mechanism of orthobunyavirus glycoprotein precursor (GPC) and the host proteases involved have not been clarified. Here we found that NSm and Gc contain their own internal signal peptides, which mediate the GPC cleavage by host signal peptidase and signal peptide peptidase (SPP). Furthermore, the NSm domain-I plays an important postcleavage role in cell fusion. Our data clarified the implication of host proteases in the processing of the orthobunyavirus GPC. This work identifies SPP as a potential intervention target, and the knowledge we gained will benefit preventive strategies against other orthobunyavirus infections.PostprintPeer reviewe

Restriction landmark genomic scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations.

BackgroundRestriction landmark genomic scanning (RLGS) is one of the most successfully applied methods for the identification of aberrant CpG island hypermethylation in cancer, as well as the identification of tissue specific methylation of CpG islands. However, a limitation to the utility of this method has been the ability to assign specific genomic sequences to RLGS spots, a process commonly referred to as "RLGS spot cloning."ResultsWe report the development of a virtual RLGS method (vRLGS) that allows for RLGS spot identification in any sequenced genome and with any enzyme combination. We report significant improvements in predicting DNA fragment migration patterns by incorporating sequence information into the migration models, and demonstrate a median Euclidian distance between actual and predicted spot migration of 0.18 centimeters for the most complex human RLGS pattern. We report the confirmed identification of 795 human and 530 mouse RLGS spots for the most commonly used enzyme combinations. We also developed a method to filter the virtual spots to reduce the number of extra spots seen on a virtual profile for both the mouse and human genomes. We demonstrate use of this filter to simplify spot cloning and to assist in the identification of spots exhibiting tissue-specific methylation.ConclusionThe new vRLGS system reported here is highly robust for the identification of novel RLGS spots. The migration models developed are not specific to the genome being studied or the enzyme combination being used, making this tool broadly applicable. The identification of hundreds of mouse and human RLGS spot loci confirms the strong bias of RLGS studies to focus on CpG islands and provides a valuable resource to rapidly study their methylation

Secretome protein signature of human pancreatic cancer stem-like cells

Emerging research has demonstrated that pancreatic ductal adenocarcinoma (PDAC) contains a sub-population of cancer stem cells (CSCs) characterized by self-renewal, anchorage-independent-growth, long-term proliferation and chemoresistance. The secretome analysis of pancreatic CSCs has not yet been performed, although it may provide insight into tumour/microenvironment interactions and intracellular processes, as well as to identify potential biomarkers. To characterize the secreted proteins of pancreatic CSCs, we performed an iTRAQ-based proteomic analysis to compare the secretomes of Panc1 cancer stem-like cells (Panc1 CSCs) and parental cell line. A total of 72 proteins were found up-/down-regulated in the conditioned medium of Panc1 CSCs. The pathway analysis revealed modulation of vital physiological pathways including glycolysis, gluconeogenesis and pentose phosphate. Through ELISA immunoassays we analysed the presence of the three proteins most highly secreted by Panc1 CSCs (ceruloplasmin, galectin-3, and MARCKS) in sera of PDAC patient. ROC curve analysis suggests ceruloplasmin as promising marker for patients negative for CA19-9.Overall, our study provides a systemic secretome analysis of pancreatic CSCs revealing a number of secreted proteins which participate in pathological conditions including cancer differentiation, invasion and metastasis. They may serve as a valuable pool of proteins from which biomarkers and therapeutic targets can be identified. Biological significance: The secretome of CSCs is a rich reservoir of biomarkers of cancer progression and molecular therapeutic targets, and thus is a topic of great interest for cancer research. The secretome analysis of pancreatic CSCs has not yet been performed. Recently, our group has demonstrated that Panc-CSCs isolated from parental cell line by using the CSC selective medium, represent a model of great importance to deepen the understanding of the biology of pancreatic adenocarcinoma. To our knowledge, this is the first proteomic study of pancreatic CSC secretome. We performed an iTRAQ-based analysis to compare the secretomes of Panc1 CSCs and Panc1 parental cell line and identified a total of 43 proteins secreted at higher level by pancreatic cancer stem cells. We found modulation of different vital physiological pathways (such as glycolysis and gluconeogenesis, pentose phosphate pathway) and the involvement of CSC secreted proteins (for example 72 kDa type IV collagenase, galectin-3, alpha-actinin-4, and MARCKS) in pathological conditions including cancer differentiation, invasion and metastasis. By ELISA verification we found that MARCKS and ceruloplasmin discriminate between controls and PDAC patients; in addition ROC curve analyses indicate that MARCKS does not have diagnostic accuracy, while ceruloplasmin could be a promising marker only for patients negative for CA19-9.We think that the findings reported in our manuscript advance the understanding of the pathways implicated in tumourigenesis, metastasis and chemoresistance of pancreatic cancer, and also identify a pool of proteins from which novel candidate diagnostic and therapeutic biomarkers could be discovered

Pannexin 1 channels facilitate communication between T cells to restrict the severity of airway inflammation

Allergic airway inflammation is driven by type-2 CD4(+) T cell inflammatory responses. We uncover an immunoregulatory role for the nucleotide release channel, Panx1, in T cell crosstalk during airway disease. Inverse correlations between Panx1 and asthmatics and our mouse models revealed the necessity, specificity, and sufficiency of Panx1 in T cells to restrict inflammation. Global Panx1(-/-) mice experienced exacerbated airway inflammation, and T-cell-specific deletion phenocopied Panx1(-/-) mice. A transgenic designed to re-express Panx1 in T cells reversed disease severity in global Panx1(-/-) mice. Panx1 activation occurred in pro-inflammatory T effector (Teff) and inhibitory T regulatory (Treg) cells and mediated the extracellular-nucleotide-based Treg-Teff crosstalk required for suppression of Teff cell proliferation. Mechanistic studies identified a Salt-inducible kinase-dependent phosphorylation of Panx1 serine 205 important for channel activation. A genetically targeted mouse expressing non-phosphorylatable Panx1S205A phenocopied the exacerbated inflammation in Panx1(-/-) mice. These data identify Panx1-dependent Treg:Teff cell communication in restricting airway disease

The American Association for the Surgery of Trauma renal injury grading scale: Implications of the 2018 revisions for injury reclassification and predicting bleeding interventions.

BackgroundIn 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions.MethodsData on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared.ResultsOf the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34).ConclusionAbout one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions.Level of evidencePrognostic and Epidemiological Study, level III

Modelling collinear and spatially correlated data

In this work we present a statistical approach to distinguish and interpret the complex relationship between several predictors and a response variable at the small area level, in the presence of i) high correlation between the predictors and ii) spatial correlation for the response. Covariates which are highly correlated create collinearity problems when used in a standard multiple regression model. Many methods have been proposed in the literature to address this issue. A very common approach is to create an index which aggregates all the highly correlated variables of interest. For example, it is well known that there is a relationship between social deprivation measured through the Multiple Deprivation Index (IMD) and air pollution; this index is then used as a confounder in assessing the e ect of air pollution on health outcomes (e.g. respiratory hospital admissions or mortality). However it would be more informative to look specically at each domain of the IMD and at its relationship with air pollution to better understand its role as a confounder in the epidemiological analyses. In this paper we illustrate how the complex relationships between the domains of IMD and air pollution can be deconstructed and analysed using pro le regression, a Bayesian non-parametric model for clustering responses and covariates simultaneously. Moreover, we include an intrinsic spatial conditional autoregressive (ICAR) term to account for the spatial correlation of the response variable

Drinking Water Salinity and Raised Blood Pressure: Evidence from a Cohort Study in Coastal Bangladesh.

BACKGROUND: Millions of coastal inhabitants in Southeast Asia have been experiencing increasing sodium concentrations in their drinking-water sources, likely partially due to climate change. High (dietary) sodium intake has convincingly been proven to increase risk of hypertension; it remains unknown, however, whether consumption of sodium in drinking water could have similar effects on health. OBJECTIVES: We present the results of a cohort study in which we assessed the effects of drinking-water sodium (DWS) on blood pressure (BP) in coastal populations in Bangladesh. METHODS: DWS, BP, and information on personal, lifestyle, and environmental factors were collected from 581 participants. We used generalized linear latent and mixed methods to model the effects of DWS on BP and assessed the associations between changes in DWS and BP when participants experienced changing sodium levels in water, switched from "conventional" ponds or tube wells to alternatives [managed aquifer recharge (MAR) and rainwater harvesting] that aimed to reduce sodium levels, or experienced a combination of these changes. RESULTS: DWS concentrations were highly associated with BP after adjustments for confounding factors. Furthermore, for each 100 mg/L reduction in sodium in drinking water, systolic/diastolic BP was lower on average by 0.95/0.57 mmHg, and odds of hypertension were lower by 14%. However, MAR did not consistently lower sodium levels. CONCLUSIONS: DWS is an important source of daily sodium intake in salinity-affected areas and is a risk factor for hypertension. Considering the likely increasing trend in coastal salinity, prompt action is required. Because MAR showed variable effects, alternative technologies for providing reliable, safe, low-sodium fresh water should be developed alongside improvements in MAR and evaluated in "real-life" salinity-affected settings. https://doi.org/10.1289/EHP659