Aim. This paper discusses the literature on establishing rigour in research studies. It describes the methodological trinity of reliability, validity and generalization and explores some of the ...issues relating to establishing rigour in naturalistic inquiry.
Background. Those working within the naturalistic paradigm have questioned the issue of using validity, reliability and generalizability to demonstrate robustness of qualitative research. Triangulation has been used to demonstrate confirmability and completeness and has been one means of ensuring acceptability across paradigms. Emerging criteria such as goodness and trustworthiness can be used to evaluate the robustness of naturalistic inquiry.
Discussion. It is argued that the transference of terms across paradigms is inappropriate; however, if we reject the concepts of validity and reliability, we reject the concept of rigour. Rejection of rigour undermines acceptance of qualitative research as a systematic process that can contribute to the advancement of knowledge. Emerging criteria for demonstrating robustness in qualitative inquiry, such as authenticity, trustworthiness and goodness, need to be considered. Goodness, when not seen as a separate construct but as an integral and embedded component of the research process, should be useful in assuring quality of the entire study. Triangulation is a tried and tested means of offering completeness, particularly in mixed‐method research. When multiple types of triangulation are used appropriately as the ‘triangulation state of mind’, they approach the concept of crystallization, which allows for infinite variety of angles of approach.
Conclusion. Qualitative researchers need to be explicit about how and why they choose specific legitimizing criteria in ensuring the robustness of their inquiries. A shift from a position of fundamentalism to a more pluralistic approach as a means of legitimizing naturalistic inquiry is advocated.
The restricted immunoglobulin (Ig) repertoire found in B-cell chronic lymphocytic leukemia (CLL) implies a role for antigen(s) in the leukemogenesis. The nature of the antigens has, however, not been ...characterized, although examples of autoantigens have been demonstrated. We have analyzed a panel of 28 CLL cell lines and primary cultures, producing monoclonal Ig with different Ig heavy-chain variable region gene usage and mutational status, including several complementarity determining region 3 homology subset members. Using mass-spectrometry, immunoassays, or protein macroarrays, we have discovered novel antigens binding to CLL Igs. These antigens included cytoskeletal proteins vimentin, filamin B, and cofilin-1, but also phosphorylcholine-containing antigens (eg, Streptococcus pneumoniae polysaccharides and oxidized low-density lipoprotein oxLDL). Additional new antigens identified were cardiolipin and proline-rich acidic protein-1. Remarkably, these antigens represent molecular motifs exposed on apoptotic cells/blebs and bacteria, and several CLL Igs bound to apoptotic Jurkat cells. In conclusion, these intriguing data, showing a limited target structure recognition, indicate that CD5+ CLL B cells are derived from a cell compartment that produces “natural antibodies,” which may be instrumental in elimination and scavenging of apoptotic cells and pathogenic bacteria.
BACKGROUND:The focus of this article is on the meanings attributed by nurses who worked with patients receiving a cancer diagnosis within acute care settings in Ireland.
OBJECTIVE:The aim of this ...article was to explore the nurses’ perceptions of caring for patients who receive bad news in the form of a cancer diagnosis while in an acute care setting.
METHODS:The article focuses on the perceptions of 20 nurses who formed the nurse participant group in a larger phenomenological study exploring giving and receiving a cancer diagnosis. Data were collected using unstructured in-depth interviews. Analysis was conducted using Koch’s analytical framework.
RESULTS:The nurses’ narratives provided 2 emerging themes entitled, “connectednessjourneying as professional within the everyday world” and “connectednessexclusion of professional within the everyday world.” This article focuses on the first emerging theme and highlights the experiences of nurses as they reflect on their interactions with their patients before, during, and after the giving of a cancer diagnosis.
CONCLUSIONS:This study highlights the importance of professional companionship. It provides insights into the nurse-patient challenges as a result of lack of information.
IMPLICATIONS FOR PRACTICE:Lack of information and involvement affects the nurse’s ability to be authentically present for the recipient and results in a fracture to the nurse-patient relationship. Understanding the experiences of nurses from acute care settings where the cancer diagnosis is often given will inform and enable the nurse working in oncology settings to engage patients in a more meaningful and focused way.
The immunoglobulin variable heavy chain (IgVH) gene mutation status is an important prognostic factor in chronic lymphocytic leukemia (CLL), since cases with mutated VH genes show significantly ...longer survival than unmutated cases. Recently, we reported a preferential use of the VH3-21 gene in mutated CLL and showed that mutated VH3-21 cases had an inferior overall survival compared with other mutated CLL. In order to further characterize this subset, we performed VH gene analysis in 265 CLL cases and identified 31 VH3-21 cases (11.7%); 21 cases had mutated and 10 cases unmutated VH genes. Regardless of VH gene mutation status, a poor overall survival was found in the VH3-21 cases with a median survival of 83 months. These survival data confirm that VH3-21 cases do not fit into the general prognostic grouping of mutated and unmutated CLL. A large fraction of VH3-21 cases also demonstrated unique features with shorter lengths of the third complementarity determining region (CDR3) and CDR3s with highly homologous amino acid sequences. Furthermore, the VH3-21 cases showed a striking dominance of λ light chain expression, and analysis of the Igλ gene rearrangements revealed highly restricted use of the Vλ2-14/Jλ3 genes in the majority of cases. Taken together, our new findings strengthen the suggestion that VH3-21–using cases comprise a new CLL entity, irrespective of VH gene mutation status, and implicate that a common antigen epitope, perhaps of pathogenic significance, is recognized by the highly homologous VH3-21/Vλ2-14 Ig molecules expressed in individual tumors.
Recent studies on the immunoglobulin variable heavy chain (IgVH) genes have revealed that B-cell chronic lymphocytic leukemia (B-CLL) consists of at least 2 clinical entities with either somatically ...mutated or unmutated VH genes. We have analyzed the VH gene mutation status and VH gene usage in 119 B-CLL cases and correlated them to overall survival. A novel finding was the preferential use of the VH3-21 gene in mutated cases, whereas biased VH1-69 gene usage was found in unmutated cases as previously reported. Interestingly, the subset of mutated cases using the VH3-21 gene displayed distinctive genotypic/phenotypic characteristics with shorter average length of the complementarity determining region 3 and clonal expression of λ light chains. In addition, this mutated subset showed significantly shorter survival than other mutated cases and a similar clinical course to unmutated cases. We therefore suggest that B-CLL cases with mutated VH3-21 genes may constitute an additional entity of B-CLL.
This article explores the process of coming to a place of knowing one's diagnosis of cancer. The study was guided by the philosophy of hermeneutic phenomenology, with data collected via unstructured ...in-depth interviews. This article focuses on 10 people who received a cancer diagnosis (recipients). The analysis of the recipient narratives offered an interpretation of the phenomenon of receiving bad news as a process occurring over a period of time and not as a one-off event in time. The concept of bad news as a trajectory was clearly evident in the narratives and was represented through 3 themes"disturbance of the everyday world," "surfacing within the lived world," and "embodiment within the lived world." The findings are consistent with the literature addressing diagnosis and end-of-life issues. Understanding the phenomenon of "knowing" is crucial in helping the healthcare professional recognize the changing information and psychosocial needs of the recipient as they experience the trajectory of bad news.
From the Department of Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden (EB, AB, IL, BR, ML and AR); Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala ...University, SE-751 85 Uppsala, Sweden (CS, GT, RR)
Correspondence: Eva Bäckman, Department of Experimental Medicine, Division of Cell Biology, Linköping University, SE-581 85 Linköping, Sweden. E-mail: eva.backman{at}ibk.liu.se
Background and Objectives: The redox-regulatory protein thioredoxin has several functions including transcriptional regulation, and antioxidant, cytokine, and chemokine activities. We have previously shown that extracellular thioredoxin protects B-cell chronic lymphocytic leukemia (CLL) cells from apoptosis in vitro . In this study we were interested to determine whether thioredoxin is produced by cells surrounding the CLL cells in the in vivo microenvironment and whether this cell-derived thioredoxin has any leukemia growth-promoting effect in vitro .
Design and Methods: Lymph nodes from CLL patients (n=25) were analyzed for thioredoxin expression by immunohistology. Stromal cells purified from the lymph nodes were analyzed for thioredoxin secretion at the single cell level using an ELIspot assay. The survival effect of the stromal-derived thioredoxin was tested by co-culturing stromal- and CLL cells with and without Fab-fragments of an anti-thioredoxin antibody.
Results: The results indicated that the thioredoxin production correlated with the amount of proliferating cells and was mainly localized to the proliferation centers (pseudofollicles) in the CLL lymph nodes. The leukemia cells per se showed minimal thioredoxin levels; in contrast, stromal cells strongly expressed thioredoxin. Purified primary stromal cells, which secreted extracellular thioredoxin, significantly protected the CLL cells from undergoing apoptosis in 72 h co-cultures. Interestingly, this anti-apoptotic effect could be abrogated by addition of Fab-fragments of an anti- thioredoxin antibody.
Interpretation and Conclusions: In conclusion, we have shown that stromal cells in the lymph node microenvironment produce thioredoxin and that the thioredoxin production is localized to the proliferation centers of the CLL lymph nodes. In addition, thioredoxin produced by purified stromal cells rescued CLL cells from apoptosis in vitro .
Key words: CLL, thioredoxin, stromal cells, microenvironment.
We report the synthesis, structure and physicochemical attributes of a new holmium(III)-based metal-organic framework whose 3D network structure gives rise to porosity; the reported structure-type ...can be varied using a range of different lanthanide ions to tune the photophysical properties and produce ligand-sensitised near-infrared (NIR) and visible light emitters.
Tri- and pentanuclear, kinetically stable SBUs were exploited for the preparation of the novel MOFs Zn(3)(BTEB)(2)(DMF)(2) and (Me(2)NH(2))Zn(5)(BTEB)(3)(μ(3)-OH)(2)(DMF)(2). The applied synthetic ...approach results in topologies that are stabilised by tritopic benzene-trisethynylbenzoic acid (BTEB) linkers giving rise to chiral frameworks with large pores or channels.
Somatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared ...with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, “stereotyped” amino acid changes occurred across the entire IGHV region in CLL subsets carrying stereotyped HCDR3 sequences, especially those expressing the IGHV3-21 and IGHV4-34 genes. These mutations are underrepresented among non-CLL sequences and thus can be considered as CLL-biased. Furthermore, it was shown that even a low level of mutations may be functionally relevant, given that stereotyped amino acid changes can be found in subsets of minimally mutated cases. The precise targeting and distinctive features of somatic hypermutation (SHM) in selected subgroups of CLL patients provide further evidence for selection by specific antigenic element(s).
PDF
