Inquiring into the Real: A Realist Phenomenological Approach

The need for postpositivist or antipositivist methods in the social sciences, including library and information science, is well documented. A promising alternative synthesizes critical realism and phenomenology. This method embraces ontological reality in all things, including human and social action. The ontology underlying the realist phenomenological approach recognizes, following Bhaskar, intransitive and transitive objects of knowledge (mind‐independent reality and individual and social perceptions of that reality). The synthesis encompasses some particular elements, including perceptions of parts and wholes, the reconciliation of presence and absence, and the essential character of intentionality. Withholding judgment (exercising a particular kind of skepticism) enables inquirers to delve into the historicity and background of action. Potential uses of the method are manifold; some specifics are examined here

Storing and sharing wisdom and traditional knowledge in the library

Traditional library practice focuses on print collections and developing collections of materials that have been published, which means the documents have gone through some kind of review or vetting process. This practice leaves a wide swath of potential knowledge out of the collection. For example, indigenous knowledge, beliefs, and experience are different, in that they do not undergo the same review or vetting process; we might refer to these types of content as wisdom. Non-print collections, such as collections of recorded oral histories, represent less traditional forms of knowledge. Human libraries push the boundaries further in the quest to integrate wisdom and lived experience into library collections. This paper delineates the relationship between wisdom and knowledge that arose during a phenomenological study of the everyday information practices of Kenyan university women. The women were asked to photograph everyday events from their life and describe what they saw. One finding was a divergent presentation of wisdom and knowledge. Because the women were describing this in relation to their education, we assert that this demonstrates a need to reconsider positivist assumptions in library science, bringing what the women called wisdom into the stacks. How, though, can wisdom be stored and shared?Includes bibliographical references

Moderators and Processes of Change in Traditional Exposure and Response Prevention (ERP) Versus Acceptance and Commitment Therapy-Informed ERP for Obsessive-Compulsive Disorder

The present study evaluated moderators and processes of change in a randomized controlled trial comparing exposure and response prevention (ERP) delivered from a traditional framework versus ERP from an acceptance and commitment therapy framework (ACT+ERP) for obsessive-compulsive disorder (OCD). This paper presents baseline, weekly session, posttreatment, and follow-up data from the study. We examined (a) moderation effects of anxiety, depression, psychological inflexibility, and interpretation of intrusions and (b) the role of psychological inflexibility and interpretation of intrusions respectively as processes of change. Participants with less dysfunctional appraisals at pretreatment performed consistently better in ERP relative to ACT+ERP. In process analyses, psychological inflexibility and interpretation of intrusions positively influenced OCD severity over time in both conditions but OCD symptom severity also positively influenced psychological inflexibility and interpretation of intrusions in both conditions. Furthermore, whereas OCD symptom severity strongly and positively predicted dysfunctional appraisals over the course of treatment in ERP, symptom severity had a weaker positive effect on dysfunctional appraisals in ACT+ERP. Clinical and theoretical implications as well as study limitations are discussed

Assessment of genotype imputation methods

Several methods have been proposed to impute genotypes at untyped markers using observed genotypes and genetic data from a reference panel. We used the Genetic Analysis Workshop 16 rheumatoid arthritis case-control dataset to compare the performance of four of these imputation methods: IMPUTE, MACH, PLINK, and fastPHASE. We compared the methods' imputation error rates and performance of association tests using the imputed data, in the context of imputing completely untyped markers as well as imputing missing genotypes to combine two datasets genotyped at different sets of markers. As expected, all methods performed better for single-nucleotide polymorphisms (SNPs) in high linkage disequilibrium with genotyped SNPs. However, MACH and IMPUTE generated lower imputation error rates than fastPHASE and PLINK. Association tests based on allele "dosage" from MACH and tests based on the posterior probabilities from IMPUTE provided results closest to those based on complete data. However, in both situations, none of the imputation-based tests provide the same level of evidence of association as the complete data at SNPs strongly associated with disease

Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data

Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomicbased approach to identify drug effects by monitoring drug-induced topology alterations. With the proposed method, drug effects are investigated under several conditions on a cell-type specific signaling network. First, starting with a generic pathway made of logical gates, we build a cell-type specific map by constraining it to fit 13 key phopshoprotein signals under 55 experimental cases. Fitting is performed via a formulation as an Integer Linear Program (ILP) and solution by standard ILP solvers; a procedure that drastically outperforms previous fitting schemes. Then, knowing the cell topology, we monitor the same key phopshoprotein signals under the presence of drug and cytokines and we re-optimize the specific map to reveal the drug-induced topology alterations. To prove our case, we make a pathway map for the hepatocytic cell line HepG2 and we evaluate the effects of 4 drugs: 3 selective inhibitors for the Epidermal Growth Factor Receptor (EGFR) and a non selective drug. We confirm effects easily predictable from the drugs’ main target (i.e. EGFR inhibitors blocks the EGFR pathway) but we also uncover unanticipated effects due to either drug promiscuity or the cell’s specific topology. An interesting finding is that the selective EGFR inhibitor Gefitinib is able to inhibit signaling downstream the Interleukin-1alpha (IL-1α) pathway; an effect that cannot be extracted from binding affinity based approaches. Our method represents an unbiased approach to identify drug effects on a small to medium size pathways and is scalable to larger topologies with any type of signaling perturbations (small molecules, 3 RNAi etc). The method is a step towards a better picture of drug effects in pathways, the cornerstone in identifying the mechanisms of drug efficacy and toxicity

Coordinated spatial and temporal expression of Hox genes during embryogenesis in the acoel Convolutriloba longifissura

Background: Hox genes are critical for patterning the bilaterian anterior-posterior axis. The evolution of their clustered genomic arrangement and ancestral function has been debated since their discovery. As acoels appear to represent the sister group to the remaining Bilateria (Nephrozoa), investigating Hox gene expression will provide an insight into the ancestral features of the Hox genes in metazoan evolution. Results: We describe the expression of anterior, central and posterior class Hox genes and the ParaHox ortholog Cdx in the acoel Convolutriloba longifissura. Expression of all three Hox genes begins contemporaneously after gastrulation and then resolves into staggered domains along the anterior-posterior axis, suggesting that the spatial coordination of Hox gene expression was present in the bilaterian ancestor. After early surface ectodermal expression, the anterior and central class genes are expressed in small domains of putative neural precursor cells co-expressing ClSoxB1, suggesting an evolutionary early function of Hox genes in patterning parts of the nervous system. In contrast, the expression of the posterior Hox gene is found in all three germ layers in a much broader posterior region of the embryo. Conclusion: Our results suggest that the ancestral set of Hox genes was involved in the anteriorposterior patterning of the nervous system of the last common bilaterian ancestor and were later co-opted for patterning in diverse tissues in the bilaterian radiation. The lack of temporal colinearity of Hox expression in acoels may be due to a loss of genomic clustering in this clade or, alternatively, temporal colinearity may have arisen in conjunction with the expansion of the Hox cluster in the Nephrozoa

Study of Z boson production in pPb collisions at √sNN=5.02 TeV

The production of Z bosons in pPb collisions at root S-NN = 5.02 TeV is studied by the CMS experiment via the electron and muon decay channels. The inclusive cross section is compared to pp collision predictions, and found to scale with the number of elementary nucleon-nucleon collisions. The differential cross sections as a function of the Z boson rapidity and transverse momentum are measured. Though they are found to be consistent within uncertainty with theoretical predictions both with and without nuclear effects, the forward-backward asymmetry suggests the presence of nuclear effects at large rapidities. These results provide new data for constraining nuclear parton distribution functions

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types