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- Baliakas, Panagiotis, et al.
(författare)
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Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study
- 2014
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Ingår i: The Lancet Haematology. - 2352-3026. ; 1:2, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets-despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separate clinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2). Interpretation The molecular classification of chronic lymphocytic leukaemia based on B-cell receptor immunoglobulin stereotypy improves the Dohner hierarchical model and refines prognostication beyond immunoglobulin mutational status, with potential implications for clinical decision making, especially within prospective clinical trials.
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- Baliakas, Panagiotis, et al.
(författare)
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Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 125:5, s. 856-859
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Tidskriftsartikel (refereegranskat)abstract
- An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.
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- Bergman, Ann, 1963-, et al.
(författare)
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Employee Availability for Work and Family : Three Swedish Case Studies
- 2007
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Ingår i: Employee relations. - : Emerald. - 0142-5455 .- 1758-7069. ; 29:4, s. 400-414
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to explore the concept of availability, both empirically and theoretically, in the context of three Swedish organisations, and identifies the structural influences on availability patterns for work and family. Design/methodology/approach - The article is based on quantitative case studies using employer records and an employee questionnaire in three organisations. Multivariate descriptive statistics and multivariate logistic regression are used to illustrate and analyse patterns of availability for work and family. Findings - The descriptive data demonstrate the influence of the organisational context and type of production process, as well as gender, on availability patterns. Patterns of work availability appeared to differ across the organisations to a greater extent than patterns of family availability, which were highly gendered. The logistic regression results indicated that: occupation was a significant influence on both temporal and spatial availability patterns across the organisations; gender was the most significant influence on time spent on household work and part-time working for parents with young children; age of employees and age of employees' children were the most significant factors influencing the use of time off work for family. Research limitations/implications - Analysis limited to case studies. More extensive quantitative research would be needed to make empirical generalisations. Qualitative research would be needed to establish whether and how employees are able to make use of different availability patterns to improve their work-life balance. Originality/value - The concept of availability is a new way of trying to capture and analyse tensions in people's everyday lives as they try to manage multiple demands.
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- Cameron, Lachlan, et al.
(författare)
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NAMAs and INDCs : Interactions and opportunities
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Countries representing more than 90 percent of global greenhouse gas emissions and population have submitted intendednationally determined contributions (INDCs) in anticipation of the 21st COP in Paris. In parallel, developing countries are designing at least 152 nationally appropriate mitigation actions (NAMAs) and 13 have secured implementation funding. Connecting these two concepts, more than a third of developing countries communicate a role for NAMAs in their INDCs. It is therefore vital to understand the potential role of NAMAs (here understood as specific actions) with respect to INDCs (which are often broader targets) and vice versa. This paper explores the links between NAMAs and INDCs with regard to various elements central to their implementation, including: access to finance; stakeholder engagement; sustainable development impacts; measurement, reporting and verification (MRV); and institutional frameworks.To avoid delaying mitigation action any further, it is important to keep momentum behind NAMAs. They represent one of the few tools at our disposal for countries to undertake mitigation actions, be recognised for these efforts, and mobilise climate finance and investment. The skills and learning on NAMA development can be seen more fundamentally as capacity for the design of bottom-up actions. Attention should be paid now to ensure that this capacity is maintained in the future. To do this, continued attention must be paid to NAMAs in Paris, as a key implementation tool for INDCs and, therefore, a key element of the success of a new global climate agreement.
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- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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