MANAGING GLOBAL VIRTUAL TEAMS: AN EXPLORATION OF OPERATION AND PERFORMANCE

As Global Virtual Teams (GVTs) operate across diverse geographies, time-zones, and cultures, they present particular problems for project management in that their characteristics may negatively affect team performance. While a significant body of research exists on project management and GVTs, previous studies have not fully elaborated on the collective impact that GVT characteristics, such as temporal distance and geographical distance, etc., have on operation and performance. This paper develops a conceptual model from existing research and generates hypotheses to explore the impact of GVT characteristics on team operations and performance. The model is then applied in a broad survey of software developers participating in GVTs. Significantly; the study found that different GVT characteristics contribute to (i) GVT operational problems and (ii) negatively impact team performance. These findings have important implications for research and GVT practitioners’ ability to operate such teams and ensure desired project outcomes

Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Objectives To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early RA inception cohorts with a focus on methotrexate (MTX) exposure. Design Multicenter prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN) Setting Secondary care, ERAS 9 centers, ERAN 23 centers in England, Wales and the Republic of Ireland Participants Patients with new diagnosis of RA, n=2701.Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3- 6 months, at 12 months and annually thereafter. Primary and secondary outcome measures Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis. Results Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any csDMARD treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (O.R. 0.85 CI 0.49, 1.49 p=0.578) and a non-significant trend for delayed ILD diagnosis (O.R. 0.54 CI 0.28, 1.06 p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (O.R. 0.48, CI 0.3, 0.79 p=0.004) and longer time to ILD diagnosis (O.R. 0.41, CI 0.23, 0.75 p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first out-patient visit. Conclusions MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary evidence suggested that MTX may delay the onset of ILD.Peer reviewe

Mapping the interaction of B cell Leukemia 3 (BCL-3) and nuclear factor κB (NF-κB) p50 identifies a BCL-3-mimetic anti-inflammatory peptide

The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease

Strain distribution in the porcine lumbar laminae under asymmetric loading

If the articular facets of the vertebra grow in an asymmetric manner, the developed geometry causes an asymmetry of loading. When the loading environment is altered by way of increased activity, the likelihood of acquiring a stress fracture may be increased. The combination of geometric asymmetry and increased activity is hypothesised to be the precursor to the stress fracture under investigation in this study, spondylolysis. This vertebral defect is an acquired fracture with 7% prevalence in the paediatric population. This value increases to 21% among athletes who participate in hyperextension sports. Tests were carried out on porcine lumbar vertebrae, on which the effect of facet angle asymmetry was simulated by offsetting the load laterally by 7mm from the mid-point. The aim of the study is to investigate whether an increase in the coronal orientation of one facet leads to an increase in strain in the corresponding vertebral lamina. Strain in the laminae was recorded using six 3-element stacked rosette strain gauges placed bilaterally. Results show that a significant linear predictive relationship exists between load offset and average strain level in the vertebral laminae with p values of 0.006 and 0.045 for principal strains e1 and e2 on the right-hand side, and p-values of 0.009 and 0.001 for principal strains e1 and e2 on the left-hand side (R2 all .0.9). This study concludes that facet angle asymmetry does lead to a difference in strain in the vertebral laminae. Change in principal strain as a result of facet asymmetry has a linear relationship and an asymmetry threshold exists beyond which compressive strain on the more coronally oriented facet can be increased by up to 15%

Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

© 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities. Methods: People from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups. Results: DAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode. Conclusion: Flares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.Peer reviewedFinal Published versio

Bifidobacterium breve with α-Linolenic Acid and Linoleic Acid Alters Fatty Acid Metabolism in the Maternal Separation Model of Irritable Bowel Syndrome

peer-reviewedThe aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (109 microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.This work was supported by the Science Foundation of Ireland – funded Centre for Science, Engineering and Technology, the Alimentary Pharmabiotic Centre

Proficiency based progression simulation training significantly reduces utility strikes:A prospective, randomized and blinded study

OBJECTIVES:We evaluated a simulation-based training curriculum with quantitatively defined performance benchmarks for utility workers location and excavation of utility services. BACKGROUND:Damaging buried utilities is associated with considerable safety risks to workers and substantial cost to employers. METHODS:In a prospective, randomized and blinded study we assessed the impact of Proficiency Based Progression (PBP) simulation training on the location and excavation of utility services work. RESULTS:PBP simulation training reduced performance errors (33%, p = 0.006) in comparison a standard trained group. When implemented across all workers in the same division there was a 35-61% reduction in utility strikes (p = 0.028) and an estimated cost saving of £116,000 -£2,175,000 in the 12 months (47,000 work hours) studied. CONCLUSIONS:The magnitude of the training benefit of PBP simulation training in the utilities sector appears to be the same as it is in surgery, cardiology and procedure-based medicine. APPLICATION:Quality-assured utility worker simulation training significantly reduces utility damage and associated costs

Discrete trajectories of resolving and persistent pain in people with rheumatoid arthritis despite undergoing treatment for inflammation: results from three UK cohorts

Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern treatments suppress inflammation, yet pain remains a major problem for many people with RA. We hypothesised that discrete RA subgroups might display favourable or unfavourable pain trajectories when receiving treatment, and that baseline characteristics will predict trajectory allocation.Growth Mixture Modelling was used to identify discrete trajectories of SF36-Bodily Pain scores during 3 years in 3 RA cohorts (Early RA Network (ERAN); n=683, British Society for Rheumatology Biologics Register Biologics (n=7090) and Non-Biologics (n=1720) cohorts. Logistic regression compared baseline predictor variables between trajectories. The role of inflammation was examined in a subgroup analysis of people with normal levels of inflammatory markers after 3 years.Mean SF36-Bodily Pain scores in each cohort improved but remained throughout 3y follow up >1 SD worse than the UK general population average. Discrete Persistent Pain (59% to 79% of cohort participants) and Resolving Pain (19% to 27%) trajectories were identified in each cohort. In ERAN, a third trajectory displaying persistently Low Pain (23%) was also identified. In people with normal levels of inflammatory markers after 3 years, 65% of them were found to follow a Persistent Pain trajectory. When trajectories were compared, greater disability (aORs 2.3-2.5 per unit baseline Health Assessment Questionnaire score) and smoking history (aORs 1.6-1.8) were risk factors for Persistent Pain trajectories in each cohort.In conclusion, distinct trajectories indicate patient subgroups with very different pain prognosis during RA treatment. Inflammation does not fully explain the pain trajectories, and non-inflammatory factors as well as acute phase response predict which trajectory an individual will follow. Targeted treatments additional to those which suppress inflammation might reduce the long term burden of arthritis pain

PL - 033 A translational model of muscle protein synthetic bioactivity in vitro, ex vivo and in vivo

Objective The aim of this research was the development and validation of a translational model for the evaluation of exercise and nutrient stimulated muscle protein synthesis (MPS). To achieve this overall aim, three primary objectives had to be realised: (i) Development of an in vitro skeletal muscle cell bioassay to measure muscle growth and MPS; (ii) Development of an ex vivo model to evaluate the humoral effect on MPS in response to nutrient feeding and exercise; (iii) Use of a stable isotope technique to evaluate MPS in response to nutrient feeding and exercise in vivo. Methods To develop a novel in vitro skeletal muscle cell bioassay to measure muscle growth and MPS, C2C12 myoblasts were proliferated and subsequently differentiated to myotubes over 8 days in DMEM (2% HS). Changes in cell behavior and adhesion properties were monitored by measuring impedance via interdigitated microelectrodes using the xCELLigence system. MPS was measured by puromycin incorporation using the SUnSET technique, intracellular signalling measured by western blot, and myotube thickness by microscopy. To demonstrate the capability to monitor nutrient regulation of muscle growth, media was conditioned with a known potent regulator of MPS (leucine) in a dose response experiment (0.20 - 2.0 mM). To establish the ability of the bioassay to measure the humoral effect of MPS in response to feeding and exercise, media was conditioned by ex vivo human serum from fasted, rested, fed (protein and isonitrogenous non-essential amino acid (NEAA) control) &nbsp;and post-exercise conditions. To evaluate MPS in response to nutrient feeding and exercise in vivo, acute MPS (5 h) was assessed by measuring stable isotope deuterium oxide (D2O) incorporation into m. vastus lateralis skeletal muscle following consumption of either a Whey Protein (WP) or an isonitrogenous NEAA control combined with resistance exercise in resistance trained males. Results In vitro experiments observed a dose-response effect with a 32 % increase in cell index and a 27 % increase in cell thickness after 2 h in the presence of 2.0 mM leucine when compared with control myotubes. Ex vivo serum following ingestion of NEAA had no effect on protein signalling or MPS whereas WP fed serum significantly increased mTOR, P70S6K and 4E-BP1 phosphorylation (p&lt;0.01, p&lt;0.05) compared to fasted serum. Furthermore, the effect of WP fed serum on protein signalling and MPS was significantly increased (p&lt;0.01, p&lt;0.05) compared to NEAA fed serum.&nbsp; Ex vivo human serum following resistance exercise was also increased MPS (29 %) and phosphorylation of mTOR (6 %), p70S6K (12 %) and 4EBP1 (7 %), compared with resting serum. These ex vivo/in vitro findings translated to the in vivo model as myofibrillar fractional synthetic rates (myoFSR) (Basal 0.068±0.002%h-1 vs. WP 0.084±0.006 %h-1, p=0.033) and absolute synthetic rates (ASR) (Basal 10.34±1.01 vs. WP 13.18±0.71 g.day-1, p=0.026) were increased from basal levels only when resistance exercise was combined with WP ingestion and not the NEAA control (NEAA MPS 0.072±0.004%h-1, NEAA ASR 10.23±0.80 g.day-1).&nbsp; Thus, ingestion of WP in combination with resistance training augments acute MPS responses in resistance trained young men. Conclusions We have developed a translational model of muscle protein synthetic bioactivity using in vitro, ex vivo and in vivo methodologies. We have shown that we can impact MPS in vitro using ex vivo human serum to condition media, that MPS in vitro is differentially regulated by ex vivo serum containing bioactive WP compared to a non-bioactive NEAA control, and that this tranlates for resistance exercise combined with WP in humans when MyoFSR is measured using stable isotope technology. &nbsp;These experiments demonstrate that ex vivo/in vitro experiments translate to the in vivo model and these methods can be used to inform both exercise and nutrient human interventions.&nbsp