Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen

Melanoma patients have high frequencies of T cells directed against antigens of their tumor. The frequency of these antitumor T cells in the blood is usually well above that of the anti-vaccine T cells observed after vaccination with tumor antigens. In a patient vaccinated with a MAGE-3 antigen presented by HLA-A1, we measured the frequencies of anti-vaccine and antitumor T cells in several metastases to evaluate their respective potential contribution to tumor rejection. The frequency of anti–MAGE-3.A1 T cells was 1.5 × 10−5 of CD8 T cells in an invaded lymph node, sixfold higher than in the blood. An antitumor cytotoxic T lymphocyte (CTL) recognizing a MAGE-C2 antigen showed a much higher enrichment with a frequency of ∼10%, 1,000 times higher than its blood frequency. Several other antitumor T clonotypes had frequencies >1%. Similar findings were made on a regressing cutaneous metastasis. Thus, antitumor T cells were ∼10,000 times more frequent than anti-vaccine T cells inside metastases, representing the majority of T cells present there. This suggests that the anti-vaccine CTLs are not the effectors that kill the bulk of the tumor cells, but that their interaction with the tumor generates conditions enabling the stimulation of large numbers of antitumor CTLs that proceed to destroy the tumor cells. Naive T cells appear to be stimulated in the course of this process as new antitumor clonotypes arise after vaccination

Job design, employment practices and well-being: a systematic review of intervention studies

There is inconsistent evidence that deliberate attempts to improve job design realise improvements in well-being. We investigated the role of other employment practices, either as instruments for job redesign or as instruments that augment job redesign. Our primary outcome was well-being. Where studies also assessed performance, we considered performance as an outcome. We reviewed 33 intervention studies. We found that well-being and performance may be improved by: training workers to improve their own jobs; training coupled with job redesign; and system wide approaches that simultaneously enhance job design and a range of other employment practices. We found insufficient evidence to make any firm conclusions concerning the effects of training managers in job redesign and that participatory approaches to improving job design have mixed effects. Successful implementation of interventions was associated with worker involvement and engagement with interventions, managerial commitment to interventions and integration of interventions with other organisational systems. Practitioner Summary: Improvements in well-being and performance may be associated with system-wide approaches that simultaneously enhance job design, introduce a range of other employment practices and focus on worker welfare. Training may have a role in initiating job redesign or augmenting the effects of job design on well-being

Stress factors and stress management interventions: the heuristic of “bottom up” an update from a systematic review

Organizations have increasingly sought to adopt innovative interventions to prevent stress-related issues. In the field of manufacturing, however, the effectiveness of these interventions remains unclear because a systematic and specific review of existing primary evidence has not been undertaken. The present systematic literature review sought to address the foregoing limitation in the literature by summarizing the main source of stress and effectiveness of stress management interventions as grounded in the context of manufacturing. Our review was limited to only randomized clinical trials (RCTs) and quasi-experimental studies and concerned employees from the manufacturing sector. Twenty-two studies on primary, secondary and tertiary interventions across four continents (Asia, Europe, USA and South America) were selected and analyzed in terms of stress factors, methodological properties and outcomes. Most of these were RCT studies (68% Vs 32%) with a majority of secondary interventions (N = 11, 50%), followed by primary (N = 5, 22%), tertiary (N = 3, 13%), and two (9%) mixed interventions. The main outcomes included an improvement of psychological wellbeing, decreased stress reactivity and an increment of general health. There was a predominance of interventions utilizing skills programs and/or cognitive-behavioral techniques. The main source of stress reported related to professional identity, organizational deficiencies, interpersonal conflicts, physical complaints and poor work environment. Taken together, the findings provide important theoretical and practical implications for advancing the study of stress factors and the use of stress management interventions in the workplace. The prerequisite for a successful intervention is to address the real problems experienced by professionals and help them to cope with their difficult situations. The strategy of “bottom-up” offers a potential means of enhancing employees’ health and well-being; however, the most effective means of implementing these interventions needs to be understood better

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed

Perspectives and Integration in SOLAS Science

Why a chapter on Perspectives and Integration in SOLAS Science in this book? SOLAS science by its nature deals with interactions that occur: across a wide spectrum of time and space scales, involve gases and particles, between the ocean and the atmosphere, across many disciplines including chemistry, biology, optics, physics, mathematics, computing, socio-economics and consequently interactions between many different scientists and across scientific generations. This chapter provides a guide through the remarkable diversity of cross-cutting approaches and tools in the gigantic puzzle of the SOLAS realm. Here we overview the existing prime components of atmospheric and oceanic observing systems, with the acquisition of ocean–atmosphere observables either from in situ or from satellites, the rich hierarchy of models to test our knowledge of Earth System functioning, and the tremendous efforts accomplished over the last decade within the COST Action 735 and SOLAS Integration project frameworks to understand, as best we can, the current physical and biogeochemical state of the atmosphere and ocean commons. A few SOLAS integrative studies illustrate the full meaning of interactions, paving the way for even tighter connections between thematic fields. Ultimately, SOLAS research will also develop with an enhanced consideration of societal demand while preserving fundamental research coherency. The exchange of energy, gases and particles across the air-sea interface is controlled by a variety of biological, chemical and physical processes that operate across broad spatial and temporal scales. These processes influence the composition, biogeochemical and chemical properties of both the oceanic and atmospheric boundary layers and ultimately shape the Earth system response to climate and environmental change, as detailed in the previous four chapters. In this cross-cutting chapter we present some of the SOLAS achievements over the last decade in terms of integration, upscaling observational information from process-oriented studies and expeditionary research with key tools such as remote sensing and modelling. Here we do not pretend to encompass the entire legacy of SOLAS efforts but rather offer a selective view of some of the major integrative SOLAS studies that combined available pieces of the immense jigsaw puzzle. These include, for instance, COST efforts to build up global climatologies of SOLAS relevant parameters such as dimethyl sulphide, interconnection between volcanic ash and ecosystem response in the eastern subarctic North Pacific, optimal strategy to derive basin-scale CO2 uptake with good precision, or significant reduction of the uncertainties in sea-salt aerosol source functions. Predicting the future trajectory of Earth’s climate and habitability is the main task ahead. Some possible routes for the SOLAS scientific community to reach this overarching goal conclude the chapter