Characterization of the monocyte-specific esterase (MSE) gene

Carboxylic esterases are widely distributed in hematopoietic cells. Monocytes express the esterase isoenzyme (termed 'monocyte-specific esterase', MSE) that can be inhibited by NaF in the alpha-naphthyl acetate cytochemical staining. We examined the expression of MSE in normal cells and primary and cultured leukemia-lymphoma cells. The MSE protein was demonstrated by isoelectric focusing (IEF); MSE mRNA expression was investigated by Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The following samples were positive for MSE protein and Northern mRNA expression: 20/24 monocytic, 4/32 myeloid, and 1/20 erythroid-megakaryocytic leukemia cell lines, but none of the 112 lymphoid leukemia or lymphoma cell lines; of the normal purified cell populations only the monocytes were positive whereas, T, B cells, and granulocytes were negative; of primary acute (myelo) monocytic leukemia cells (CD14-positive, FAB M4/M5 morphology) 14/20 were Northern mRNA and 11/14 IEF protein positive. RT-PCR revealed MSE expression in 29/49 Northern-negative lymphoid leukemia-lymphoma cell lines. The RT-PCR signals in monocytic cell lines were on average 50-fold stronger than the mostly weak trace expression in lymphoid specimens. On treatment with various biomodulators, only all-trans retinoic acid significantly upregulated MSE message and protein levels but could not induce new MSE expression in several leukemia cell lines; lipopolysaccharide and interferon-gamma increased MSE expression in normal monocytes. Analysis of DNA methylation with sensitive restriction enzymes showed no apparent regulation of gene expression by differential methylation; the MSE gene is evolutionarily conserved among mammalian species; the half-life of the human MSE transcripts was about 5-6 h. The extent of MSE expression varied greatly among different monocytic leukemia samples. However, the MSE overexpression in a significant number of specimens was not associated with gene amplification, gross structural rearrangements or point mutations within the cDNA region. Taken together, the results suggest that MSE expression is not absolutely specific for, but strongly associated with cells of the monocytic lineage; MSE is either not expressed at all or expressed at much lower levels in cells from other lineages. The biological significance, if any, of rare MSE messages in lymphoid cells detectable only by the hypersensitive RT-PCR remains unclear. Further studies on the regulation of this gene and on the physiological function of the enzyme will no doubt be informative with respect to its striking overexpression in some malignant cells and to a possible role in the pathobiology of monocytic leukemias

IcePAC – a probabilistic tool to study sea ice spatio-temporal dynamics: application to the Hudson Bay area

A reliable knowledge and assessment of the sea ice conditions and their evolution in time is a priority for numerous decision makers in the domains of coastal and offshore management and engineering as well as in commercial navigation. As of today, countless research projects aimed at both modelling and mapping past, actual and future sea ice conditions were completed using sea ice numerical models, statistical models, educated guesses or remote sensing imagery. From this research, reliable information helping to understand sea ice evolution in space and in time is available to stakeholders. However, no research has, until present, assessed the evolution of sea ice cover with a frequency modelling approach, by identifying the underlying theoretical distribution describing the sea ice behaviour at a given point in space and time. This project suggests the development of a probabilistic tool, named IcePAC, based on frequency modelling of historical 1978–2015 passive microwave sea ice concentrations maps from the EUMETSAT OSI-409 product, to study the sea ice spatio-temporal behaviour in the waters of the Hudson Bay system in northeast Canada. Grid-cell-scale models are based on the generalized beta distribution and generated at a weekly temporal resolution. Results showed coherence with the Canadian Ice Service 1981–2010 Sea Ice Climatic Atlas average freeze-up and melt-out dates for numerous coastal communities in the study area and showed that it is possible to evaluate a range of plausible events, such as the shortest and longest probable ice-free season duration, for any given location in the simulation domain. Results obtained in this project pave the way towards various analyses on sea ice concentration spatio-temporal distribution patterns that would gain in terms of information content and value by relying on the kind of probabilistic information and simulation data available from the IcePAC tool.</p

Tension at the borders: perceptions of role overload, conflict, strain and facilitation in work, family and health roles among employed individuals with arthritis

Objective. To examine inter-relationships among arthritis (A), work (W) and personal life (P) roles and their reciprocal influences, especially experiences of role balance/imbalance among individuals with inflammatory arthritis (IA) and OA

Crocodylian head width allometry and phylogenetic prediction of body size in extinct crocodyliforms

Body size and body-size shifts broadly impact life-history parameters of all animals, which has made accurate body-size estimates for extinct taxa an important component of understanding their paleobiology. Among extinct crocodylians and their precursors (e.g., suchians), several methods have been developed to predict body size from suites of hard-tissue proxies. Nevertheless, many have limited applications due to the disparity of some major suchian groups and biases in the fossil record. Here, we test the utility of head width (HW) as a broadly applicable body-size estimator in living and fossil suchians. We use a dataset of sexually mature male and female individuals

Measuring patient perceptions about osteoporosis pharmacotherapy

Abstract Background Adherence to osteoporosis pharmacotherapy is poor, and linked with patient perceptions of the benefits of, and barriers to taking these treatments. To better understand the association between patient perceptions and osteoporosis pharmacotherapy, we generated thirteen items that may tap into patient perceptions about the benefits of, and barriers to osteoporosis treatment; and included these items as part of a standardized telephone interview of women aged 65–90 years (n = 871). The purpose of this paper is to report the psychometric evaluation of our scale. Findings Upon detailed analysis, six of the thirteen items were omitted: four redundant, one did not correlate well with any other item and one factorial complex. From the remaining seven items, two distinct unidimensional domains emerged (variance explained = 78%). Internal consistency of the 5-item osteoporosis drug treatment benefits domain was good (Cronbach's alpha = 0.88), and was supported by construct validity; women reporting a physician-diagnosis or taking osteoporosis pharmacotherapy had higher osteoporosis treatment benefit scores compared to those reporting no osteoporosis diagnosis or treatment respectively. Because only two items were identified as tapping into treatment barriers, we recommend they each be used as a separate item assessing potential barriers to adherence to osteoporosis pharmacotherapy, rather than combined into a single scale. Conclusion The 5-item osteoporosis drug treatment benefits scale may be useful to examine perceptions about the benefits of osteoporosis pharmacotherapy. Further research is needed to develop scales that adequately measure perceived barriers to osteoporosis pharmacotherapy

The effect on work presenteeism of job retention vocational rehabilitation compared to a written self-help work advice pack for employed people with inflammatory arthritis: protocol for a multi-centre randomised controlled trial (the WORKWELL trial)

Abstract: Background: Work problems are common in people with inflammatory arthritis. Up to 50% stop work within 10 years due to their condition and up to 67% report presenteeism (i.e. reduced work productivity), even amongst those with low disease activity. Job retention vocational rehabilitation (JRVR) may help prevent or postpone job loss and reduce presenteeism through work assessment, work-related rehabilitation and enabling job accommodations. This aims to create a better match between the person’s abilities and their job demands. The objectives of the Workwell trial are to test the overall effectiveness and cost-effectiveness of JRVR (WORKWELL) provided by additionally trained National Health Service (NHS) occupational therapists compared to a control group who receive self-help information both in addition to usual care. Methods: Based on the learning from a feasibility trial (the WORK-IA trial: ISRCTN76777720), the WORKWELL trial is a multi-centre, pragmatic, individually-randomised parallel group superiority trial, including economic evaluation, contextual factors analysis and process evaluation. Two hundred forty employed adults with rheumatoid arthritis, undifferentiated inflammatory arthritis or psoriatic arthritis (in secondary care), aged 18 years or older with work instability will be randomised to one of two groups: a self-help written work advice pack plus usual care (control intervention); or WORKWELL JRVR plus a self-help written work advice pack and usual care. WORKWELL will be delivered by occupational therapists provided with additional JRVR training from the research team. The primary outcome is presenteeism as measured using the Work Limitations Questionnaire-25. A comprehensive range of secondary outcomes of work, health, contextual factors and health resource use are included. Outcomes are measured at 6- and 12- months (with 12-months as the primary end-point). A multi-perspective within-trial cost-effectiveness analyses will also be conducted. Discussion: This trial will contribute to the evidence base for provision of JRVR to people with inflammatory arthritis. If JRVR is found to be effective in enabling people to keep working, the findings will support decision-making about provision of JRVR by rheumatology teams, therapy services and healthcare commissioners, and providing evidence of the effectiveness of JRVR and the economic impact of its implementation. Trial registration: Clinical Trials.Gov: NCT03942783. Registered 08/05/2019 (https://clinicaltrials.gov/ct2/show/NCT03942783); ISRCTN Registry: ISRCTN61762297. Registered:13/05/2019 (http://www.isrctn.com/ISRCTN61762297). Retrospectively registered