Is Quantitative Research Ethical? Tools for Ethically Practicing, Evaluating, and Using Quantitative Research

This editorial offers new ways to ethically practice, evaluate, and use quantitative research (QR). Our central claim is that ready-made formulas for QR, including 'best practices' and common notions of 'validity' or 'objectivity,' are often divorced from the ethical and practical implications of doing, evaluating, and using QR for specific purposes. To focus on these implications, we critique common theoretical foundations for QR and then recommend approaches to QR that are 'built for purpose,' by which we mean designed to ethically address specific problems or situations on terms that are contextually relevant. For this, we propose a new tool for evaluating the quality of QR, which we call 'relational validity.' Studies, including their methods and results, are relationally valid when they ethically connect researchers' purposes with the way that QR is oriented and the ways that it is done—including the concepts and units of analysis invoked, as well as what its 'methods' imply more generally. This new way of doing QR can provide the liberty required to address serious worldly problems on terms that are both practical and ethically informed in relation to the problems themselves rather than the confines of existing QR logics and practices.cited By

General mutation databases : analysis and review

Databases of mutations causing Mendelian disease play a crucial role in research, diagnostic and genetic health care and can play a role in life and death decisions. These databases are thus heavily used, but only gene or locus specific databases have been previously reviewed for completeness, accuracy, currency and utility. We have performed a review of the various general mutation databases that derive their data from the published literature and locus specific databases. Only two&mdash;the Human Gene Mutation Database (HGMD) and Online Mendelian Inheritance in Man (OMIM)&mdash;had useful numbers of mutations. Comparison of a number of characteristics of these databases indicated substantial inconsistencies between the two databases that included absent genes and missing mutations. This situation strengthens the case for gene specific curation of mutations and the need for an overall plan for collection, curation, storage and release of mutation data.<br /

High Glucose Attenuates Shear-Induced Changes in Endothelial Hydraulic Conductivity by Degrading the Glycocalyx

Diabetes mellitus is a risk factor for cardiovascular disease; however, the mechanisms through which diabetes impairs homeostasis of the vasculature have not been completely elucidated. The endothelium interacts with circulating blood through the surface glycocalyx layer, which serves as a mechanosensor/transducer of fluid shear forces leading to biomolecular responses. Atherosclerosis localizes typically in regions of low or disturbed shear stress, but in diabetics, the distribution is more diffuse, suggesting that there is a fundamental difference in the way cells sense shear forces. In the present study, we examined the effect of hyperglycemia on mechanotranduction in bovine aortic endothelial cells (BAEC). After six days in high glucose media, we observed a decrease in heparan sulfate content coincident with a significant attenuation of the shear-induced hydraulic conductivity response, lower activation of eNOS after exposure to shear, and reduced cell alignment with shear stress. These studies are consistent with a diabetes-induced change to the glycocalyx altering endothelial response to shear stress that could affect the distribution of atherosclerotic plaques

COL4A5 and LAMA5 variants co-inherited in familial hematuria: Digenic inheritance or genetic modifier effect?

Background: About 40-50% of patients with familial microscopic hematuria (FMH) caused by thin basement membrane nephropathy (TBMN) inherit heterozygous mutations in collagen IV genes (COL4A3, COL4A4). On long follow-up, the full phenotypic spectrum of these patients varies a lot, ranging from isolated MH or MH plus low-grade proteinuria to chronic renal failure of variable degree, including end-stage renal disease (ESRD). Methods: Here, we performed Whole Exome Sequencing (WES) in patients of six families, presenting with autosomal dominant FMH, with or without progression to proteinuria and loss of renal function, all previously found negative for severe collagen IV mutations. Hierarchical filtering of the WES data was performed, followed by mutation prediction analysis, Sanger sequencing and genetic segregation analysis. Results: In one family with four patients, we found evidence for the contribution of two co-inherited variants in two crucial genes expressed in the glomerular basement membrane (GBM); LAMA5-p.Pro1243Leu and COL4A5-p.Asp654Tyr. Mutations in COL4A5 cause classical X-linked Alport Syndrome, while rare mutations in the LAMA5 have been reported in patients with focal segmental glomerulosclerosis. The phenotypic spectrum of the patients includes hematuria, proteinuria, focal segmental glomerulosclerosis, loss of kidney function and renal cortical cysts. Conclusions: A modifier role of LAMA5 on the background of a hypomorphic Alport syndrome causing mutation is a possible explanation of our findings. Digenic inheritance is another scenario, following the concept that mutations at both loci more accurately explain the spectrum of symptoms, but further investigation is needed under this concept. This is the third report linking a LAMA5 variant with human renal disease and expanding the spectrum of genes involved in glomerular pathologies accompanied by familial hematurias. The cystic phenotype overlaps with that of a mouse model, which carried a Lama5 hypomorphic mutation that caused severely reduced Lama5 protein levels and produced kidney cysts. 2018 The Author(s).The work was supported from the Cyprus Research Promotion Foundation through the grant NEW INFRASTRUCTURE/STRATEGIC/0308/24 to CD (co-funded by the European Regional Development Fund and the Republic of Cyprus). The funding body did not contribute to the design of study, collection, analysis and interpretation of data, or in manuscript writing.Scopu

An Ethnographer Lured into Darkness

No matter the combination of methods ethnographers bring to their research design and to participant observation, our pursuit to log, interpret, analyse and present the lives of those we meet is never an entirely intellectual or objective one. Ethnographic fieldwork is intimately sensory (Pink, Doing sensory ethnography, Sage, London, 2015), invokes our imagination (Sparkes, Qualitative research in sport and exercise, 1:21–35, 2009) and requires us to actively navigate social landscapes (Hammersley and Atkinson, Field relations. Ethnography: Principles in practice, Routledge, Stoodleigh, 2007). There is a tendency for these elements to fade in terms of visibility and immediacy within the research process. For those in accord with (Davies, Reflexive ethnography: A guide to researching selves and others, Routledge, New York, 2008), continuous reflexive labour becomes a core praxis to monitor the ways we observe and participate in this textured environment. Without this, we are left in the dark and are less able to see how we can (or should) respond to the nitty–gritty qualitative nature of ethnography. In this Chapter, two of methodological vignettes will act as entry points to unpack a set of tensions that commanded my attention during an eighteen months ethnography in Higher Education. ‘You Look Like an Ivory Tower Student’, for example, begins to troubleshoot ethnographic participation within educational environments. ‘Going Dark’, on the other hand, problematises the prioritisation of visual observations that are implicit in ethnographic tradition. Throughout these discussions a metaphor of being lured into darkness is offered as a productive orientation for ethnography

Epistatic Role of the MYH9/APOL1 Region on Familial Hematuria Genes.

Familial hematuria (FH) is explained by at least four different genes (see below). About 50% of patients develop late proteinuria and chronic kidney disease (CKD). We hypothesized that MYH9/APOL1, two closely linked genes associated with CKD, may be associated with adverse progression in FH. Our study included 102 thin basement membrane nephropathy (TBMN) patients with three known COL4A3/COL4A4 mutations (cohort A), 83 CFHR5/C3 glomerulopathy patients (cohort B) with a single CFHR5 mutation and 15 Alport syndrome patients (cohort C) with two known COL4A5 mild mutations, who were categorized as "Mild" (controls) or "Severe" (cases), based on renal manifestations. E1 and S1 MYH9 haplotypes and variant rs11089788 were analyzed for association with disease phenotype. Evidence for association with "Severe" progression in CFHR5 nephropathy was found with MYH9 variant rs11089788 and was confirmed in an independent FH cohort, D (cumulative p value = 0.001, odds ratio = 3.06, recessive model). No association was found with APOL1 gene. Quantitative Real time PCR did not reveal any functional significance for the rs11089788 risk allele. Our results derive additional evidence supporting previous reports according to which MYH9 is an important gene per se, predisposing to CKD, suggesting its usefulness as a prognostic marker for young hematuric patients

Forced Solid-State Interactions for the Selective “Turn-On” Fluorescence Sensing of Aluminum Ions in Water Using a Sensory Polymer Substrate

Selective and sensitive solid sensory substrates for detecting Al(III) in pure water are reported. The material is a flexible polymer film that can be handled and exhibits gel behavior and membrane performance. The film features a chemically anchored salicylaldehyde benzoylhydrazone derivative as an aluminum ion fluorescence sensor. A novel procedure for measuring Al(III) at the ppb level using a single solution drop in 20 min was developed. In this procedure, a drop was allowed to enter the hydrophilic material for 15 min before a 5 min drying period. The process forced the Al(III) to interact with the sensory motifs within the membrane before measuring the fluorescence of the system. The limit of detection of Al(III) was 22 ppm. Furthermore, a water-soluble sensory polymer containing the same sensory motifs was developed with a limit of detection of Al(III) of 1.5 ppb, which was significantly lower than the Environmental Protection Agency recommendations for drinking water.Spanish Ministerio de Economía y Competitividad-Feder (MAT2011-22544) and by the Consejería de Educación - Junta de Castilla y León (BU232U13)

The role of molecular genetics in diagnosing familial hematuria(s)

Familial microscopic hematuria (MH) of glomerular origin represents a heterogeneous group of monogenic conditions involving several genes, some of which remain unknown. Recent advances have increased our understanding and our ability to use molecular genetics for diagnosing such patients, enabling us to study their clinical characteristics over time. Three collagen IV genes, COL4A3, COL4A4, and COL4A5 explain the autosomal and X-linked forms of Alport syndrome (AS), and a subset of thin basement membrane nephropathy (TBMN). A number of X-linked AS patients follow a milder course reminiscent of that of patients with heterozygous COL4A3/COL4A4 mutations and TBMN, while at the same time a significant subset of patients with TBMN and familial MH progress to chronic kidney disease (CKD) or end-stage kidney disease (ESKD). A mutation in CFHR5, a member of the complement factor H family of genes that regulate complement activation, was recently shown to cause isolated C3 glomerulopathy, presenting with MH in childhood and demonstrating a significant risk for CKD/ESKD after 40 years old. Through these results molecular genetics emerges as a powerful tool for a definite diagnosis when all the above conditions enter the differential diagnosis, while in many at-risk related family members, a molecular diagnosis may obviate the need for another renal biopsy

From Data to Causes III: Bayesian Priors for General Cross-Lagged Panel Models (GCLM)

This article describes some potential uses of Bayesian estimation for time-series and panel data models by incorporating information from prior probabilities (i.e., priors) in addition to observed data. Drawing on econometrics and other literatures we illustrate the use of informative “shrinkage” or “small variance” priors (including so-called “Minnesota priors”) while extending prior work on the general cross-lagged panel model (GCLM). Using a panel dataset of national income and subjective well-being (SWB) we describe three key benefits of these priors. First, they shrink parameter estimates toward zero or toward each other for time-varying parameters, which lends additional support for an income → SWB effect that is not supported with maximum likelihood (ML). This is useful because, second, these priors increase model parsimony and the stability of estimates (keeping them within more reasonable bounds) and thus improve out-of-sample predictions and interpretability, which means estimated effect should also be more trustworthy than under ML. Third, these priors allow estimating otherwise under-identified models under ML, allowing higher-order lagged effects and time-varying parameters that are otherwise impossible to estimate using observed data alone. In conclusion we note some of the responsibilities that come with the use of priors which, departing from typical commentaries on their scientific applications, we describe as involving reflection on how best to apply modeling tools to address matters of worldly concern