Insufficient Effort Responding

The quality of self-report data has long been a concern, with increasing attention to the issue of insufficient effort responding (IER). Researchers have made considerable progress in developing techniques for handling IER (Meade & Craig, 2012; Huang, Bowling, Liu, & Li, 2014). This dissertation examines the use of IER best practices in survey research within the management literature through a series of essays. The results of the first study indicate that there is a lack of methodological transparency regarding how IER is addressed in the management literature. Simply stated, few authors report addressing IER in their manuscripts; thus, no conclusions could be drawn regarding management researchers use of IER best practices. Based on the findings of Study 1, the aim of Study 2 was to investigate this lack of reporting through a job performance lens. The essay explored several potential reasons for low methodological transparency regarding IER practices, including (1) insufficient KSAs (i.e., understanding or awareness of IER best practices), thus IER was not addressed nor reported, and (2) a lack of extrinsic motivation to report how IER was addressed in studies (i.e., reviewer requirements and page limitations). The results of Study 2 indicate that though management researchers do not report utilizing IER technique, IER is being addressed in various ways by management researchers. The most common techniques management researchers use to address IER are employing infrequency technique items to detect IER and deleting respondents flagged by the detection method from samples. Taken as a whole, these findings suggest there is room for improvement regarding how IER is addressed in management research using self-report survey data. Subsequently, Study 3 introduces a technique for examining and addressing the effects of IER on data quality that does not require researchers to delete respondent data, which may inadvertently bias samples or eliminate otherwise “good” data. Specifically, the final essay demonstrates how to create an IER method factor that can be used to examine the effects of IER detected in a sample and control for the effects of IER if it appears to bias research conclusions

COS-P som hjelpetiltak i barnevernet. Delrapport 5 prosjekt «Virkning av hjelpetiltak i barnevernet»

Denne rapporten handler om bruken av foreldreveiledningsprogrammet Circle of Security (COS-P) i barnevernet og er en delrapport i prosjektet «Virkning av hjelpetiltak i barnevernet». Studien bygger på flere metodiske tilnærminger. Vi har gjennomført en litteraturgjennomgang, kvalitative intervjuer med ansatte i barneverntjenesten, og foreldre som har gjennomført COS-P som et tiltak i barnevernet. Studien bygger også på et feltarbeid i flere barneverntjenester der vi har vært til stede på drøftingsmøter i barneverntjenesten. I tillegg har vi gjennomført en studie av barnevernmapper, og gjort observasjoner i et gruppetilbud med COS-P.publishedVersio

Styrket og tidligere tilbud til småbarnsforeldre. Systematisk samarbeid mellom helsestasjon og familievernkontor. Evaluering av Tiltak 26 i «En god barndom varer livet ut». Tiltaksplan for å bekjempe vold og seksuelle overgrep mot barn og ungdom (2014-2017)

Myndighetene ønsker å bedre barns oppvekstvilkår gjennom å bidra til gode og lett tilgjengelige tjenester for å styrke kvaliteten i samliv, samt forebygge samlivskonflikter og samlivsbrudd. Helsestasjonene og familieverntjenesten står sammen i en særstilling når det gjelder mulighet til å bidra til gode parforhold for å fremme barnas beste. Barne-, ungdoms- og familiedirektoratet (Bufdir) har i samarbeid med Helsedirektoratet (Hdir) hatt ansvar for å gjennomføre et treårig prøveprosjekt med systematisk samarbeid mellom disse tjenestene. Oppdraget er formulert i tiltak 26 i «En god barndom varer livet ut. Tiltaksplan for å bekjempe vold og seksuelle overgrep mot barn og ungdom (2014-2017)». Prosjektet har vart i perioden 2015-2017. VID vitenskapelige høgskole har evaluert prøveprosjektetpublishedVersio

Identification of Genetic and Epigenetic Variations in a Rat Model for Neurodevelopmental Disorders

A combination of genetic variations, epimutations and environmental factors may be involved in the etiology of complex neurodevelopmental disorders like schizophrenia. To study such disorders, we use apomorphine-unsusceptible (APO-UNSUS) Wistar rats and their phenotypic counterpart apomorphine-susceptible (APO-SUS) rats that display a complex phenotype remarkably similar to that of schizophrenic patients. As the molecular basis of the APO-SUS/UNSUS rat model, we recently identified a genomic rearrangement of the Aph-1b gene. Here, we discovered between the two rat lines differences other than the Aph-1b gene defect, including a remarkable cluster of genetic variations, two variants corresponding to topoisomerase II-based recombination hot spots and an epigenetic (DNA methylation) difference in cerebellum and (hypo)thalamic but not hippocampal genomic DNA. Furthermore, genetic variations were found to correlate with the degree of apomorphine susceptibility in unselected Wistar rats. Together, the results show that a number of genetic and epigenetic differences exist between the APO-SUS and -UNSUS rat genomes, raising the possibility that in addition to the Aph-1b gene defect the newly identified variations may also contribute to the complex APO-SUS phenotype

Clioquinol Inhibits Zinc-Triggered Caspase Activation in the Hippocampal CA1 Region of a Global Ischemic Gerbil Model

Background: Excessive release of chelatable zinc from excitatory synaptic vesicles is involved in the pathogenesis of selective neuronal cell death following transient forebrain ischemia. The present study was designed to examine the neuroprotective effect of a membrane-permeable zinc chelator, clioquinol (CQ), in the CA1 region of the gerbil hippocampus after transient global ischemia. Methodology/Principal Findings: The common carotid arteries were occluded bilaterally, and CQ (10 mg/kg, i.p.) was injected into gerbils once a day. The zinc chelating effect of CQ was examined with TSQ fluorescence and autometallography. Neuronal death, the expression levels of caspases and apoptosis inducing factor (AIF) were evaluated using TUNEL, in situ hybridization and Western blotting, respectively. We were able to show for the first time that CQ treatment attenuates the ischemia-induced zinc accumulation in the CA1 pyramidal neurons, accompanied by less neuronal loss in the CA1 field of the hippocampus after ischemia. Furthermore, the expression levels of caspase-3,-9, and AIF were significantly decreased in the hippocampus of CQ-treated gerbils. Conclusions/Significance: The present study indicates that the neuroprotective effect of CQ is related to downregulation o

Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells

INTRODUCTION: A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison. METHODS: Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage. RESULTS: When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis. CONCLUSION: The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper

Endogenous Zinc in Neurological Diseases

The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early