301 research outputs found
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Unison, workplace learning and enhancing learning network theory : a case study
Following a review of the UK's long term skill requirements in 2006 (Leitch 2006), the government has been looking at ways to increase the UK's skills base through employer engagement in training and education. Trade unions and higher education institutions have had a vital role in this process through the establishment of a wide variety of collaborative projects aimed at enhancing basic, intermediate and higher skills. One example of such a partnership is the Learning Partnership Route (LPR) to Social Work qualification. Whilst a number of authors have detailed the role of trade unions in work-based learning partnerships with public sector organisations, including in social care (see, for example, Sutherland and Rainbird 2000), there is a shortage of academic literature relating specifically to UNISON's role in informal learning in these organisations. This research study uses a case study method applying a critical realist approach, to look in depth at one social care organisation in which the LPR was run. The key theory utilised for data analysis is the Learning Network Theory (LNT) (Poell et al 2000). The LNT is one theory which has been put forward to describe organisational learning in the literature and uses the actors, structures and processes to interpret and describe how learning is organised. The case study findings revealed how Unison's trusting relationship with the social care employer and their coherent notion of the concept of a learning organisation, enabled them to become involved in both formal and informal aspects of workplace learning. Evidence is also presented to critique and enhance the LNT, extending the LNT to incorporate the concepts of formal and informal learning
Prison(er) auto/biography, 'true crime', and teaching, learning, and research in criminology
The main aim of this essay is to explore prisoner life writing within the specific, richly and multiply dependent context of teaching and learning undergraduate criminology at an English university, from the authorial viewpoint of a teacher and her students as budding criminologists and co-authors. This article seeks to redress a continuing resistance to life history approaches in the teaching of criminology, despite the discipline being formally devoted to the understanding of the meaning and experience of imprisonment in all its forms and consequences. What follows is a trucated narrative of what students had to say on the fascinating subjects of prisoner auto/biography and its place in popular and expert discourses on crime, criminality, and punishment, contextualised within the academic discipline of criminology
Bridging Opportunities in Human Health Services
The Campus to Community project aims to develop facilitated, in-depth site visits for VCU faculty and staff interested in exploring human health services opportunities in the Richmond community. The site visit experience will provide exposure to various community organizations specializing in human health, essentially creating a âbridgeâ between VCUâs campus and these facilities. This initiative is intended to motivate employees to action within the Richmond community by enabling them to observe first-hand the services that these organizations provide, learn more about the organizationsâ missions, and engage in meaningful interactions with representatives on site. Likewise, it will allow Richmond community organizations to discuss unique needs and opportunities for partnerships with VCU
Influence Of DNA On The Rate Of Porphyrin Metallation
Poly(dGâdC)â and poly(dAâdT)â have marked influences on the rate of insertion of copper(II) into cationic porphyrins reflecting the interaction mode of the porphyrin with the nucleic acid
Managing unusual sensory experiences: A feasibility trial in an At Risk Mental States for psychosis group
Objectives To conduct a feasibility study on a new, tablet-delivered treatment for unusual sensory experiences in service-users with an At Risk Mental States for psychosis. Design A mixed method design was employed, using content analysis to investigate whether service-users and therapists found the new treatment acceptable and helpful. We also collected data on the impact of treatment, but without a control group could not make any claims about effectiveness. Methods Eligible participants were contacted before starting treatment and offered the chance to participate. Assessments were conducted before and after the treatment, which typically was completed in 4â6 sessions by an accredited CBT therapist. A structured interview was used to collect qualitative feedback. Results Qualitative feedback suggested that the treatment was acceptable to service-users and therapists, and the progression criteria were met for recruitment, retention, and adherence to treatment. Conclusions The new treatment targeting subtypes of auditory and visual hallucinations was acceptable to service-users and the benefits of addressing psychological mechanisms thought to contribute to hallucinations was supported by qualitative feedback
Macrophage Differentiation and Polarization Regulate the Release of the Immune Checkpoint Protein V-Domain Ig Suppressor of T Cell Activation.
Recently, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) was identified as a negative immune checkpoint regulator (NCR) that is mainly expressed in hematopoietic cells. Preclinical studies have shown that VISTA blockade results in impeded tumor growth and improved survival. Nevertheless, little is known about the physiological role of VISTA expression in macrophages. This study focused on the differential expression of VISTA in human monocytes and macrophages in order to elucidate a putative role of VISTA regulation upon macrophage polarization and activation. We observed that human peripheral monocytes constitutively release soluble VISTA, which was regulated via matrix metalloproteinases. However, monocyte stimulation with cytokines that induce macrophage differentiation, such as granulocyte-macrophage colony-stimulating (GM-CSF) and macrophage colony-stimulating factor (M-CSF), substantially reduced soluble VISTA release. VISTA release was further affected by various pro- and anti-inflammatory stimuli that led to macrophage polarization, where activated M1 macrophages generally released more VISTA than M2 macrophages. Additionally, we observed that stimulation of activated macrophages with the toll-like receptor 4 ligand lipopolysaccharide (LPS) led to a further decrease of soluble VISTA release. Moreover, we found that soluble VISTA impairs T cell cytotoxic activity but did not induce their programmed death. Our results suggest that VISTA is constantly produced and released in the peripheral blood where it may contribute to peripheral tolerance
Effects of a novel, brief psychological therapy (Managing Unusual Sensory Experiences) for hallucinations in first episode psychosis (MUSE FEP): findings from an exploratory randomised controlled trial.
Hallucinations are a common feature of psychosis, yet access to effective psychological treatment is limited. The Managing Unusual Sensory Experiences for First-Episode-Psychosis (MUSE-FEP) trial aimed to establish the feasibility and acceptability of a brief, hallucination-specific, digitally provided treatment, delivered by a non-specialist workforce for people with psychosis. MUSE uses psychoeducation about the causal mechanisms of hallucinations and tailored interventions to help a person understand and manage their experiences. We undertook a two-site, single-blind (rater) Randomised Controlled Trial and recruited 82 participants who were allocated 1:1 to MUSE and treatment as usual (TAU) (n=40) or TAU alone (n=42). Participants completed assessments before and after treatment (2 months), and at follow up (3-4 months). Information on recruitment rates, adherence, and completion of outcome assessments was collected. Analyses focussed on feasibility outcomes and initial estimates of intervention effects to inform a future trial. The trial is registered with the ISRCTN registry 16793301. Criteria for the feasibility of trial methodology and intervention delivery were met. The trial exceeded the recruitment target, had high retention rates (87.8%) at end of treatment, and at follow up (86.6%), with good acceptability of treatment. There were 3 serious adverse events in the therapy group, and 5 in the TAU group. Improvements were evident in both groups at the end of treatment and follow up, with a particular benefit in perceived recovery in the MUSE group. We showed it was feasible to increase access to psychological intervention but a definitive trial requires further changes to the trial design or treatment
T lymphocytes induce human cancer cells derived from solid malignant tumors to secrete galectin-9 which facilitates immunosuppression in cooperation with other immune checkpoint proteins.
BACKGROUND
Galectin-9 is a member of the family of lectin proteins and crucially regulates human immune responses, particularly because of its ability to suppress the anticancer activities of T lymphocytes and natural killer cells. Recent evidence demonstrated that galectin-9 is highly expressed in a wide range of human malignancies including the most aggressive tumors, such as high-grade glioblastomas and pancreatic ductal adenocarcinomas, as well as common malignancies such as breast, lung and colorectal cancers. However, solid tumor cells at rest are known to secrete either very low amounts of galectin-9 or, in most of the cases, do not secrete it at all. Our aims were to elucidate whether T cells can induce galectin-9 secretion in human cancer cells derived from solid malignant tumors and whether this soluble form displays higher systemic immunosuppressive activity compared with the cell surface-based protein.
METHODS
A wide range of human cancer cell lines derived from solid tumours, keratinocytes and primary embryonic cells were employed, together with helper and cytotoxic T cell lines and human as well as mouse primary T cells. Western blot analysis, ELISA, quantitative reverse transcriptase-PCR, on-cell Western and other measurement techniques were used to conduct the study. Results were validated using in vivo mouse model.
RESULTS
We discovered that T lymphocytes induce galectin-9 secretion in various types of human cancer cells derived from solid malignant tumors. This was demonstrated to occur via two differential mechanisms: first by translocation of galectin-9 onto the cell surface followed by its proteolytic shedding and second due to autophagy followed by lysosomal secretion. For both mechanisms a protein carrier/trafficker was required, since galectin-9 lacks a secretion sequence. Secreted galectin-9 pre-opsonised T cells and, following interaction with other immune checkpoint proteins, their activity was completely attenuated. As an example, we studied the cooperation of galectin-9 and V-domain Ig-containing suppressor of T cell activation (VISTA) proteins in human cancer cells.
CONCLUSION
Our results underline a crucial role of galectin-9 in anticancer immune evasion. As such, galectin-9 and regulatory pathways controlling its production should be considered as key targets for immunotherapy in a large number of cancers
Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-ÎČ1 - Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes.
Immune checkpoint proteins play crucial roles in human embryonic development but are also used by cancer cells to escape immune surveillance. These proteins and biochemical pathways associated with them form a complex machinery capable of blocking the ability of cytotoxic immune lymphoid cells to attack cancer cells and, ultimately, to fully suppress anti-tumor immunity. One of the more recently discovered immune checkpoint proteins is V-domain Ig-containing suppressor of T cell activation (VISTA), which plays a crucial role in anti-cancer immune evasion pathways. The biochemical mechanisms underlying regulation of VISTA expression remain unknown. Here, we report for the first time that VISTA expression is controlled by the transforming growth factor beta type 1 (TGF-ÎČ)-Smad3 signaling pathway. However, in T lymphocytes, we found that VISTA expression was differentially regulated by TGF-ÎČ depending on their immune profile. Taken together, our results demonstrate the differential biochemical control of VISTA expression in human T cells and various types of rapidly proliferating cells, including cancer cells, fetal cells and keratinocytes
AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.
Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (
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