1,964 research outputs found
Care, control and the electroconvulsive therapy (ECT) ritual: Making sense of polarised patient narratives
Despite evidence of short-term effectiveness of ECT (electroconvulsive therapy), both positive and negative patient reports are common. However, research examining these polarized accounts has not adequately elucidated why such divergences occur. We thus sought to examine opposing patient narratives to better understand underlying meanings. Eighteen interviews were conducted with UK-based people who had experienced the treatment. Our analysis revealed that the quality of relations with staff, ECT artefacts (e.g. the ECT suite), and perceived outcomes all play a role in divergent accounts. Positive reflections on ECT emerged alongside narratives of trust in staff, comfort with ECT, and perception of sufficient personal control. Conversely, where negative evaluations of ECT predominated, there was anger associated with a lack of control, and a belief that ECT made little sense, and was linked to past abuses and/or the unacceptability of side effects. We discuss the implications of our findings for professionals
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Advancing the business and human rights agenda: Dialogue, empowerment, and constructive engagement
As corporations are going global, they are increasingly confronted with human rights challenges. As such, new ways to deal with human rights challenges in corporate operations must be developed as traditional governance mechanisms are not always able to tackle them. This article presents five different views on innovative solutions for the relationships between business and human rights that all build on empowerment, dialogue and constructive engagement. The different approaches highlight an emerging trend toward a more active role for corporations in the protection of human rights. The first examines the need for enhanced dialogue between corporations and their stakeholders. The next three each examine a different facet of empowerment, a critical factor for the respect and protection of human rights: empowerment of the poor, of communities, and of consumers. The final one presents a case study of constructive corporate engagement in Myanmar (Burma). Altogether, these research projects provide insight into the complex relationships between corporate operations and human rights, by highlighting the importance of stakeholder dialogue and empowerment. All the five projects were presented during the Second Swiss Master Class in Corporate Social Responsibility, held in Lausanne, Switzerland on December 12, 2008. The audience for this conference, which examined business and human rights, was composed of researchers, governmental representatives, and business and non-governmental organization practitioners
Paravertebral block as a sole technique for the anaesthetic management of a patient with myalgic encephalomyelitis undergoing breast cancer surgery
Myalgic encephalomyelitis (ME) is a multifaceted organic disease which, owing to its non-specific multiple symptoms that include incapacitating fatigue, deeply affects the quality of life of diseased patients. It carries a perceived risk of an adverse reaction to drugs, including anaesthetics. However, there is very little information in the medical literature on the anaesthetic management and outcomes of patients with this condition. According to current scientific literature, there is no causal relationship between ME relapse and anaesthesia, surgery or both. We present the anaesthetic management of a ME patient who underwent breast cancer surgery.Keywords: breast cancer surgery, chronic fatigue syndrome, myalgic encephalomyelitis, paravertebral bloc
NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss
Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.
Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PSâ
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1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint.
Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SDâ
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6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SDâ
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6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Grâ
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3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm.
Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss
Displaced but not replaced: the impact of e-learning on academic identities in higher education.
Challenges facing universities are leading many to implement institutional strategies to incorporate e-learning rather than leaving its adoption up to enthusiastic individuals. Although there is growing understanding about the impact of e-learning on the student experience, there is less understanding of academicsâ perceptions of e-learning and its impact on their identities. This paper explores the changing nature of academic identities revealed through case study research into the implementation of e-learning at one UK university. By providing insight into the lived experiences of academics in a university in which technology is not only transforming access to knowledge but also influencing the balance of power between academic and student in knowledge production and use, it is suggested that academics may experience a jolt to their âtrajectory of selfâ when engaging with e-learning. The potential for e-learning to prompt loss of teacher presence and displacement as knowledge expert may appear to undermine the ontological security of their academic identity
High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease.
BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95Â % CI 2.5-14.5, pâ=â0.004) with high resolution CT. In the multivariate analysis ethnicity (pâ=â0.02) and disease state (pâ<â0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95Â % CI 2.5-14.5, pâ=â0.004) and in HAM/TSP patients compared with all other categories 8.4 (95Â % CI 2.7-26.1, pâ=â0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95Â % 1.2-9.7, pâ=â0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4Â %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis
Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome
Long-distance axonal trafficking plays a critical role in neuronal function and transport defects have been linked to neurodegenerative disorders. Various lines of evidence suggest that the small GTPase Rab5 plays a role in neuronal signaling via early endosomal transport. Here, we characterized the motility of Rab5 endosomes in primary cultures of mouse hippocampal pyramidal cells by live-cell imaging and showed that they exhibit bi-directional long-range motility in axons, with a strong bias toward retrograde transport. Characterization of key Rab5 effectors revealed that endogenous Rabankyrin-5, Rabenosyn-5 and APPL1 are all present in axons. Further analysis of APPL1-positive endosomes showed that, similar to Rab5-endosomes, they display more frequent long-range retrograde than anterograde movement, with the endosomal levels of APPL1 correlated with faster retrograde movement. Interestingly, APPL1-endosomes transport the neurotrophin receptor TrkB and mediate retrograde axonal transport of the kinase Akt1. FRET analysis revealed that APPL1 and Akt1 interact in an endocytosis-dependent manner. We conclude that Rab5-APPL1 endosomes exhibit the hallmarks of axonal signaling endosomes to transport Akt1 in hippocampal pyramidal cells
Adopting human factors in early phase and experimental medicine research: a nested pilot study observing controlled human infection with SARS-CoV-2
Aims
The influence of human factors on safety in healthcare settings is well established, with targeted interventions reducing risk and enhancing team performance. In experimental and early phase clinical research participant safety is paramount and safeguarded by guidelines, protocolized care and staff training; however, the real-world interaction and implementation of these risk-mitigating measures has never been subjected to formal system-based assessment.
Methods
Independent structured observations, systematic review of study documents, and interviews and focus groups were used to collate data on three key tasks undertaken in a clinical research facility (CRF) during a SARS CoV-2 controlled human infection model (CHIM) study. The Systems Engineering Initiative for Patient Safety (SEIPS) was employed to analyse and categorize findings, and develop recommendations for safety interventions.
Results
High levels of team functioning and a clear focus on participant safety were evident throughout the study. Despite this, latent risks in both study-specific and CRF work systems were identified in all four SEIPS domains (people, environment, tasks and tools). Fourteen actionable recommendations were generated collaboratively. These included inter-organization and inter-study standardization, optimized checklists for safety critical tasks, and use of simulation for team training and exploration of work systems.
Conclusions
This pioneering application of human factors techniques to analyse work systems during the conduct of research in a CRF revealed risks unidentified by routine review and appraisal, and despite international guideline adherence. SEIPS may aid categorization of system problems and the formulation of recommendations that reduce risk and mitigate potential harm applicable across a trials portfolio
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