Miracle-dz/UniFAR-FTUs huggingface dataset:
Do we need validity ? — A critical appraisal of validity in qualitative research

Author: Per Kihlgren Master thesis SOCM04 30hp Supervisor: Veronika Burcar Department of sociology, spring term 2016 Background: Validity is understood to be a question of the correctness or accuracy of research. It can be viewed as a condition for science’s aspiration to produce authoritative knowledge. When it comes to qualitative research, the claims produced are often interpretations of people’s way of understanding. The validity of qualitative research can therefore be viewed as particularly difficult to affirm. Purpose: The purpose of this thesis is to review literature on validity in qualitative research. It also discusses the literature in relation to using it in assessment of research. Literature was collected through extensive searches in method books on qualitative research and databases. The focus is on research in sociology. Results: Validity in qualitative research has been understood, among other things, as truth, accurate representation and adequacy. It has also been reconceptualized as concerning success in practice and acknowledgement of multiple possible interpretations. An attractive solution to the problem of validity is to equate it with that findings can be trusted to use in further research. A common theme is that validity is dependent on consensus, e.g., consensus concerning the meaning and application of concepts. Problems with consensus is that it can be hard to reach, standards based on it may be hard to practice, and it can also stop innovation. Conclusion: A workable and mutual concept of validity is possible if there is consensus within a research community on, e.g., concepts and their application. However, such a consensus may block new interpretations and work as a “policing” of a research field. Instead, conceptions of validity should be treated as incitements to research. Moreover, a generic conception of validity, independent of what purpose the research should serve, is not possible. Still, transparency and honesty is generally called for, since they facilitate the evaluation of research.
Mixed Proteasomes Function To Increase Viral Peptide Diversity and Broaden Antiviral CD8+ T Cell Responses

The three proteasome subunits with proteolytic activity are encoded by standard or immunoproteasome genes. Many proteasomes expressed by normal cells and cells exposed to cytokines are “mixed”, that is, contain both standard and immunoproteasome subunits. Using a panel of 38 defined influenza A virus–derived epitopes recognized by C57BL/6 mouse CD8+ T cells, we used mice with targeted disruption of β1i, β2i, or β5i/β2i genes to examine the contribution of mixed proteasomes to the immunodominance hierarchy of antiviral CD8+ T cells. We show that each immunoproteasome subunit has large effects on the primary and recall immunodominance hierarchies due to modulating both the available T cell repertoire and generation of individual epitopes as determined both biochemically and kinetically in Ag presentation assays. These findings indicate that mixed proteasomes function to enhance the diversity of peptides and support a broad CD8+ T cell response.
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.

Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacologic approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs, and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this review, we illustrate how dietary and pharmacologic therapies differ in their effect on tumor growth, proliferation, and metabolism and discuss the available preclinical and clinical evidence in favor of or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics. SIGNIFICANCE To our knowledge, this is the first review article that comprehensively analyzes the preclinical and preliminary clinical experimental foundations of both dietary and pharmacologic metabolic interventions in cancer therapy. Among several promising therapies, we propose treatment personalization on the basis of tumor genetics, tumor metabolism, and patient systemic metabolism.Cancer Discov; 6(12); 1315-33. ©2016 AACR.
Single-phase/-stage PFC AC/DC converter based on the integration of interleaved DCM boost converter and three-level DC-DC topology composed by the series connection of two half-bridge converters

A single-phase single-stage high power factor AC/DC converter based on the integration of interleaved DCM boost converter and three-level DC-DC topology composed by the series connection of two isolated half-bridge converters is proposed in this paper. The DC-DC isolated converters operate in CCM with ZVS commutation in all switches and the three-level structure configuration allows the operation with reduced switch voltage and the use of lower voltage rating devices. The input interleaved boost converters operate in DCM and the input current follows the input voltage waveform without an input current control loop. The input current also presents low current ripple due to the interleaved operation. The control of the integrated converter is obtained using an asymmetrical PWM modulation and a balance capacitor is used in order to maintain the voltage balance in the primary bus capacitors. The performance of the isolated rectifier is tested with a prototype with 1 kW output power, 127 V input voltage, 200 V output voltage and 40 kHz switching frequency.
Serotype-specific interactions among functional domains of dengue virus 2 nonstructural proteins (NS) 5 and NS3 are crucial for viral RNA replication

Four serotypes of mosquito-borne dengue virus (DENV), evolved from a common ancestor, are human pathogens of global significance for which there is no vaccine or antiviral drug available. The N-terminal domain of DENV NS5 has guanylyltransferase and methyltransferase (MTase), and the C-terminal region has the polymerase (POL), all of which are important for 5′-capping and RNA replication. The crystal structure of NS5 shows it as a dimer, but the functional evidence for NS5 dimer is lacking. Our studies showed that the substitution of DENV2 NS5 MTase or POL for DENV4 NS5 within DENV2 RNA resulted in a severe attenuation of replication in the transfected BHK-21 cells. A replication-competent species was evolved with the acquired mutations in the DENV2 and DENV4 NS5 MTase or POL domain or in the DENV2 NS3 helicase domain in the DENV2 chimera RNAs by repeated passaging of infected BHK-21 or mosquito cells. The linker region of seven residues in NS5, rich in serotype-specific residues, is important for the recovery of replication fitness in the chimera RNA. Our results, taken together, provide genetic evidence for a serotype-specific interaction between NS3 and NS5 as well as specific interdomain interaction within NS5 required for RNA replication. Genome-wide RNAseq analysis revealed the distribution of adaptive mutations in RNA quasispecies. Those within NS3 and NS5 are located at the surface and/or within the NS5 dimer interface, providing a functional significance to the crystal structure NS5 dimer.
Metacognitive capacity and negative symptoms in first episode psychosis: Evidence of a prospective relationship over a 3-year follow-up

Negative symptoms can be linked to Bleuler’s concept of splitting or fragmentation of thought, affect, and will. Research has shown a link between disturbances in metacognition and negative symptoms, although relatively few studies have examined this relationship longitudinally. The aim of this article is to examine whether metacognitive capacity among patients with first episode psychosis (FEP) predicted negative symptoms after a follow-up period of 3 years. Metacognition was assessed using the Metacognition Assessment Scale abbreviated and symptoms were assessed using Positive and Negative Syndrome Scale among 59 adults with FEP. Symptoms were then reassessed at a 3-year follow-up. Significant correlations were found between baseline metacognitive scores and the expressive component of negative symptoms as well as for individual negative symptoms such as blunted affect, poor rapport, and alogia at 3-year follow-up after controlling for baseline negative symptoms. Self-reflectivity was significantly correlated with the expressive component of negative symptoms at 3-year follow-up. The results are partly consistent with a Bleulerian model which understands the emergence of negative symptoms as a response in part to the experience of fragmentation, particularly in terms of sense of self and others. Future research should clarify the likely role of metacognition in the development and maintenance of negative symptoms.
Motivational influences on impression formation: outcome dependency, accuracy-driven attention, and individuating processes.

How might being outcome dependent on another person influence the processes that one uses to form impressions of that person? We designed three experiments to investigate this question with respect to short-term, task-oriented outcome dependency. In all three experiments, subjects expected to interact with a young man formerly hospitalized as a schizophrenic, and they received information about the person's attributes in either written profiles or videotapes. In Experiment 1, short-term, task-oriented outcome dependency led subjects to use relatively individuating processes (i.e., to base their impressions of the patient on his particular attributes), even under conditions that typically lead subjects to use relatively category-based processes (i.e., to base their impressions on the patient's schizophrenic label). Moreover, in the conditions that elicited individuating processes, subjects spent more time attending to the patient's particular attribute information. Experiment 2 demonstrated that the attention effects in Experiment 1 were not merely a function of impression positivity and that outcome dependency did not influence the impression formation process when attribute information in addition to category-level information was unavailable. Finally, Experiment 3 manipulated not outcome dependency but the attentional goal of forming an accurate impression. We found that accuracy-driven attention to attribute information also led to individuating processes. The results of the three experiments indicate that there are important influences of outcome dependency on impression formation. These results are consistent with a model in which the tendency for short-term, task-oriented outcome dependency to facilitate individuating impression formation processes is mediated by an increase in accuracy-driven attention to attribute information.
Oral medicine modification for older adults: a qualitative study of nurses

Objective Oral medicines are frequently modified (eg, tablets crushed) for older adults. However, these modifications can have clinical, legal and/or ethical implications. Nurses bear responsibility for medicine administration and hence, perform these modifications. The aim of this study was to investigate the knowledge, attitudes and beliefs of nurses about oral medicine modification for older adults. Design A qualitative study was conducted using semi-structured, face-to-face interviews with nurses providing care to older adults in acute and long-term care settings. Interviews were audio-recorded, transcribed verbatim and analysed thematically. Settings Sixteen purposively selected care settings; 4 acute-care and 12 long-term care settings were included. Nurses were recruited by convenience sampling at these sites. Participants Eighteen nurses participated (83% female, 67% long-term care, 33% acute-care, median age (IQR) 38 years (32.5–52.0)). Results Three major themes: modifying—a necessary evil, nurses’ role as patient advocate and modifying—we are working very much as a team and two minor themes: fractional dosing, and covert administration emerged from the data. Nurses viewed oral medicine modifications as being a routine and necessary occurrence in geriatric patient care due to limitations of available formulations and the presence of age-related challenges in drug administration. Nurses’ knowledge of residents’ requirements ensured that they advocate for those with individualised formulation needs, however, nurses rely on pharmacists for information about modifications. Nurses expressed a desire for supports including increased education and ward-specific, pharmacist-developed recommendations on common modifications. Conclusions This study has provided useful insights into the views of nurses regarding oral medicine modification for older adults. The unique and varied formulation requirements of older adults must be acknowledged. Increased engagement by healthcare professionals, the pharmaceutical industry, regulatory agencies and policy-makers is required to facilitate the development of age-appropriate formulations. In the interim, practical interventions, informed by the findings of this study, are required.
Wedelolactone inhibits adipogenesis through the ERK pathway in human adipose tissue‐derived mesenchymal stem cells

Wedelolactone is an herbal medicine that is used to treat septic shock, hepatitis and venom poisoning. Although in differentiated and cancer cells, wedelolactone has been identified as anti‐inflammatory, growth inhibitory, and pro‐apoptotic, the effects of wedelolactone on stem cell differentiation remain largely unknown. Here, we report that wedelolactone inhibits the adipogenic differentiation of human adipose tissue‐derived mesenchymal stem cells (hAMSCs). Wedelolactone reduced the formation of lipid droplets and the expression of adipogenesis‐related proteins, such as CCAAT enhancer‐binding protein‐α (C/EBP‐α), peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), lipoprotein lipase (LPL), and adipocyte fatty acid‐binding protein aP2 (aP2). Wedelolactone mediated this process by sustaining ERK activity. In addition, inhibition of ERK activity with PD98059 resulted in reversion of the wedelolactone‐mediated inhibition of adipogenic differentiation. Taken together, these results indicate that wedelolactone inhibits adipogenic differentiation through ERK pathway and suggest a novel inhibitory effect of wedelolactone on adipogenic differentiation in hAMSCs. J. Cell. Biochem. 113: 3436–3445, 2012. © 2012 Wiley Periodicals, Inc.
Hip pain and mobility deficits--hip osteoarthritis: clinical practice guidelines linked to the international classification of functioning, disability, and health from the orthopaedic section of the American Physical Therapy Association.

The Orthopaedic Section of the American Physical Therapy Association presents this third set of clinical practice guidelines on hip osteoarthritis, linked to the International Classification of Functioning, Disability, and Health (ICF). The purpose of these practice guidelines is to describe evidence-based orthopaedic physical therapy clinical practice and provide recommendations for (1) examination and diagnostic classification based on body functions and body structures, activity limitations, and participation restrictions, (2) prognosis, (3) interventions provided by physical therapists, and (4) assessment of outcome for common musculoskeletal disorders. J Orthop Sports Phys Ther 2009;39(4):A1-A25. doi:10.2519/jospt.2009. 0301
A Multilevel Functional Study of a SNAP25 At-Risk Variant for Bipolar Disorder and Schizophrenia

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25, rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b/SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala–ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal–limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia. SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically the SNAP25 protein, may be involved in psychiatric disorders. Here, our multilevel functional studies are bringing strong evidence for the functional consequences of an allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal–limbic network. These results demonstrate a common genetically driven functional alteration of a synaptic mechanism both in schizophrenia and early-onset bipolar disorder and confirm the shared genetic vulnerability between these two disorders.
Analysis of Subcarinal Lymph Nodes in (Suspected) Non-Small-Cell Lung Cancer after a Negative Transbronchial Needle Aspiration – What’s Next?

Background: Transbronchial needle aspiration (TBNA) of subcarinal lymph nodes (LN) has a variable yield. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has demonstrated a high accuracy in the analysis of enlarged subcarinal LN. Objective: To assess the diagnostic accuracy of EUS-FNA in the analysis of enlarged subcarinal LN previously staged tumor negative by TBNA. Methods and Patients: In this retrospective study, we included all patients with (suspected) lung cancer and enlarged (>1 cm on CT) subcarinal LNs staged tumor negative by TBNA, who were subsequently staged by EUS-FNA. In addition, surgical-pathological information had to be available in those cases in which EUS-FNA was tumor negative. Results: Subcarinal LN metastases were assessed by EUS-FNA in 10 of 14 patients (71%). In 1 patient granulomas without necrosis were found. The remaining 3 patients staged tumor negative by both TBNA and EUS-FNA had reactive LN tissue, which was confirmed by surgical-pathological staging. Sensitivity, specificity and diagnostic accuracy of EUS in analyzing TBNA-negative LNs was 100% in all. Conclusions: In patients with (suspected) lung cancer and enlarged subcarinal LNs staged tumor negative by TBNA, additional staging by EUS-FNA confirmed subcarinal LN metastasis in 71% of the patients. These data suggest that for the analysis of the subcarinal LNs the real-time controlled technique of EUS-FNA is superior to the ‘blind’ technique of TBNA.
Temperature-dependent Arrest of Neutrophil Apoptosis

Apoptosis is essential for the resolution of neutrophilic inflammation. To define the mechanisms triggering the execution phase of apoptosis we developed and utilized a model in which culture of human neutrophils at 15 °C for 20 h arrested apoptosis and subsequent warming to 37 °C triggered a synchronous burst of apoptosis. Treatment of 15 °C cultured neutrophils with the pan-caspase inhibitor zVAD-fmk just before warming to 37 °C inhibited the morphological changes associated with apoptosis, but did not prevent the insertion of the proapoptotic protein Bax into mitochondria nor the inhibition of secretion and the externalization of phosphatidylserine, indices of neutrophil apoptosis. In both intact neutrophils and a cell-free extract, cytochrome c released from mitochondria induced proteolytic cleavage of procaspase-3. At 15 °C the binding of Bax to mitochondria was uncoupled from Bax insertion into the mitochondrial membrane required for the release of cytochrome c. Apoptosis was also inhibited by low pH during warming to 37 °C, suggesting that changes to the conformation of Bax, necessary for membrane insertion, were being inhibited. Bax insertion was only sensitive to zVAD-fmk when added at the start of the 15 °C culture period, suggesting that a cytoplasmic substrate of the effector caspases may mediate in the mechanism of Bax insertion into mitochondria.
Human-action recognition using a multi-layered fusion scheme of Kinect modalities

This study addresses the problem of efficiently combining the joint, RGB and depth modalities of the Kinect sensor in order to recognise human actions. For this purpose, a multi-layered fusion scheme concatenates different specific features, builds specialised local and global SVM models and then iteratively fuses their different scores. The authors essentially contribute in two levels: (i) they combine the performance of local descriptors with the strength of global bags-of-visual-words representations. They are able then to generate improved local decisions that allow noisy frames handling. (ii) They also study the performance of multiple fusion schemes guided by different features concatenations, Fisher vectors representations concatenation and later iterative scores fusion. To prove the efficiency of their approach, they have evaluated their experiments on two challenging public datasets: CAD-60 and CGC-2014. Competitive results are obtained for both benchmarks.