Compassion Stress and the Qualitative Researcher

Human subjects are carefully protected in the research process. However, the same consideration is not currently being given to the qualitative researcher, even those investigating topics that are likely to elicit powerful emotions. The role of researcher’s emotional responses and the self-care strategies that, in some circumstances, are appropriate for the researcher and other research support personnel have not received the attention they deserve in qualitative research literature. Based on experience in conducting research on the topic of self-directed learning and breast cancer, and on the limited literature available, the author makes the case for the use of strategies such as counseling, peer debriefing, and journal writing as means of dealing with the potential for “compassion stress” as experienced by the researcher and other research support personnel. She also suggests that the preparation of social science researchers should include information on appropriate self-care strategies.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Kinome and Transcriptome Profiling Reveal Broad and Distinct Activities of Erlotinib, Sunitinib, and Sorafenib in the Mouse Heart and Suggest Cardiotoxicity From Combined Signal Transducer and Activator of Transcription and Epidermal Growth Factor Receptor Inhibition

BACKGROUND: Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. METHODS AND RESULTS: We administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks. We then compared the effects of these 3 kinase inhibitors on the cardiac transcriptome using RNAseq and the cardiac kinome using multiplexed inhibitor beads coupled with mass spectrometry. We found unexpectedly broad molecular effects of all 3 kinase inhibitors, suggesting that target kinase selectivity does not define either the molecular response or the potential for cardiotoxicity. Using in vivo drug administration and primary cardiomyocyte culture, we also show that the cardiosafety of erlotinib treatment may result from upregulation of the cardioprotective signal transducer and activator of transcription 3 pathway, as co-treatment with erlotinib and a signal transducer and activator of transcription inhibitor decreases cardiac contractile function and cardiomyocyte fatty acid oxidation. CONCLUSIONS: Collectively our findings indicate that preclinical kinome and transcriptome profiling may predict the cardiotoxicity of novel kinase inhibitors, and suggest caution for the proposed therapeutic strategy of combined signal transducer and activator of transcription/epidermal growth factor receptor inhibition for cancer treatment

Der Konflikt in Afghanistan : Historischer und gesellschaftlicher Hintergrund, Evolution und Lageentwicklung – ein Positionspapier

This study is part of a larger project, the aim of which is to elucidate “mental health nurses” attitudes towards their patients'. In this study, nurses' and patients' attitudes are described from the perspective of both parties using a qualitative approach. The informants were selected from a rehabilitation unit for young adults, below 40, suffering from psychosis at a psychiatric clinic that provides acute psychiatric care. The informant group consisted of three dyads: three patients with various diagnoses and three nurses with primary responsibility for the patients' daily care. The aim of this particular study was to extend our preliminary understanding of nurses' attitudes towards psychiatric patients in the context of psychiatric in-patient care, by elucidating the patient's “inner” picture of her/his past, present and future and the nurse's picture of the same patient's past, present and future. Data were collected and analysed using a phenomenological-hermeneutic approach and the narrative picturing technique. For each picture and group, 15 related sub-themes emerged, on the basis of which six themes were formulated. The findings show that the nurses overrate their own importance when it comes to the patient's well-being on the ward. All the nurses emphasize confirmation and safety as the basis of their nursing care, while in the patient's picture the nurses represent a replication of childhood demands, which probably means that nursing care risks becoming a continuation of the patient's childhood estrangement

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

Narrative constructions of anorexia and abuse: An athlete's search for meaning in trauma

Interpretive approaches to the study of eating disorders are scarce. Narrative analysis provides an attractive means to address this shortfall and is applied to the life story of Beth, a former elite athlete with experience of anorexia nervosa and, as she revealed, sexual abuse. Six unstructured life history interviews took place yielding more than 9 hours of interview data. Throughout our conversations, Beth constructed multiple, fragile, and sometimes contrasting narrative coherences indicative of a fragmented and uncertain understanding of her life. It is argued that how Beth makes sense of her trauma is consequential for her future experiences

Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex

Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment. In preclinical models MEK inhibition induced genome-wide enhancer formation involving the seeding of BRD4, MED1, H3K27 acetylation and p300 that drives transcriptional adaptation. Inhibition of P-TEFb associated proteins BRD4 and CBP/p300 arrested enhancer seeding and RTK upregulation. BRD4 bromodomain inhibitors overcame trametinib resistance, producing sustained growth inhibition in cells, xenografts and syngeneic mouse TNBC models. Pharmacological targeting of P-TEFb members in conjunction with MEK inhibition by trametinib is an effective strategy to durably inhibit epigenomic remodeling required for adaptive resistance