Autopilot? A reflexive review of the piloting process in qualitative e-research

Purpose: This paper examines an oft-neglected aspect of qualitative research practice – conducting a pilot – using the innovative approach of ‘e-research’ to generate both practical and methodological insights. Approach: Using the authors’ ‘e-research’ pilot as a reflexive case study, key methodological issues are critically reviewed. This review is set in a broader context of the qualitative methods literature in which piloting appears largely as an implicit practice. Using a new and emerging approach (‘e-research’) provides a prompt to review our ‘autopilot’ tendencies and offers a new lens for analysing research practice. Findings: We find that despite an initial focus on ‘practical’ aspects of data collection within our ‘e-research’, the pilot opened up a range of areas for further consideration. We review research ethics, collaborative research practices and data management issues specifically for e-research but also reflect more broadly on potential implications for piloting within other research designs. Practical implications: We aim to offer both practical and methodological insights for qualitative researchers, whatever their methodological orientation, so that they might develop approaches for piloting that are appropriate to their own research endeavours. More specifically, we offer tentative guidance to those venturing into the emerging area of ‘e-research’. Value: This paper offers insight into an oft-ignored aspect of qualitative research, whilst also engaging in emerging area of methodological interest

Stratigraphic framework of the late Miocene Pisco Formation at Cerro Los Quesos (Ica Desert, Peru)

The enormous concentration of marine vertebrates documented within the Pisco Formation is unique for Peru and South America and places this unit among the prime fossil Lagerstätten for Miocene to Pliocene marine mammals worldwide. In order to provide a robust stratigraphic framework for the fossil-bearing locality of Cerro Los Quesos, this study presents a 1:10,000 scale geological map covering an area of about 21 km2, a detailed measured section spanning 290 m of strata, and a refined chronostratigraphy for the studied succession well constrained by diatom biostratigraphy and high-resolution 40Ar/39Ar isotopic dating of three interbedded ash layers. Within the apparently monotonous, diatomite-dominated sedimentary section, the Pisco Formation has been subdivided into six local members, with stratigraphic control over the different outcrops facilitated by the establishment of a detailed marker bed stratigraphy based on fifteen readily distinguishable sediment layers of different nature

Effect of hyperbaric oxygenation and gemcitabine on apoptosis of pancreatic ductal tumor cells in vitro.

Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells. Materials and Methods: PANC-1 and AsPc-1 PDAC tumor cell lines wereused. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) and HBO at 2.5 ATA for 90 min or a combination of both (HBO then GEM and GEM then HBO). Twenty-four hours later, apoptotic cells ineach group were analyzed and the apoptotic index (AI) wascalculated. Results: PANC-1 cell line: HBO alone had noeffect on AI: 6.5\ub10.1 vs. 5.9\ub10.1. HBO before and aftergemcitabine did not further increase AI: 8.2\ub10.1 (HBOGEM),8.5\ub10.1 (GEM-HBO) vs. 8.1\ub10.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7\ub10.02 (p<0.001 vs. all groups). AsPc-1 cell line: HBO-alone had no effect on AI: 5.9\ub10.1 vs. 5.9\ub10.1. HBO before and after gemcitabine did not further increase AI:8.2\ub10.1 (HBO-GEM), 8.4\ub10.1 (GEM-HBO) vs. 8.0\ub10.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7\ub10.1 (p<0.001 vs. all groups). Conclusion: HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cellsin vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy

Mapping Protein Structure Changes with Cysteine Labeling Kinetics by Mass Spectrometry

Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide "system" inertia-really difficult to be overcome-and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE) in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of "fertilizing a patient engagement ecosystem": an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient "disengagement" is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Managing participatory action research in a health-care service experiencing conflicts

Purpose \u2013 The purpose of the paper is to explore why it was considered useful and how it was possible to conduct a participatory action research (PAR) in a health-care service experiencing conflictual dynamics (which affected service quality) and on the challenges this entailed. Specific attention is given to the action researchers\u2019 role. Design/methodology/approach \u2013 A methodological reflection is developed starting from theoretical considerations and a case study. In response to the committee group\u2019s request concerning the need to better understand and manage the criticalities and conflict episodes faced by a service for sufferers of Alzheimer\u2019s disease, the authors proposed and realized a PAR. The PAR is described considering: the process, some outcomes, the functions and actions performed by the action researchers, and the dilemmas and challenges they faced. Findings \u2013 The case study revealed it was fundamental for the action researchers to perform a constant mediating function when conducting a PAR in an organization experiencing conflictual dynamics. How this function was carried out is described. Furthermore, the dilemmas, challenges and risks faced by the action researchers in proposing this PAR are addressed. Research limitations/implications \u2013 In this PAR the main limitations and open issues concern both the possibility of assessing outcomes and processes in a medium to long time frame and the cyclical turnover of patients and caregivers, raising the question of legacy. Originality/value \u2013 In analyzing a specific case, the authors focus upon both the indicators that allowed them to assess usefulness, feasibility and sustainability of the PAR in a conflictual context and the functions assumed, actions realized, and challenges faced by the action researchers