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While industry platforms can transform industries and drive the digital economy, little guidance exists to help managers decide which industry platform to join. Derived from industry research, we propose a six-step return-on-participa- tion (ROP) method that enables managers to clearly and logically review how their firms are affected by a platform, what the benefits are, how current and future var- iable and fixed costs vary, as well as the often-hidden joining costs. We suggest this technique could also be used by managers to compare competing platforms and by platform owners to evaluate the attractiveness of their offerings.

We have sequenced the chloroplast genome of red spruce (Picea rubens) for the first time using the single-end, short-reads (44 bp) Illumina sequences, assembled and functionally annotated it, and identified simple sequence repeats (SSRs). The contigs were assembled using SOAPdenovo2 following the retrieval of chloroplast genome sequences using the black spruce (Picea mariana) chloroplast genome as the reference. The assembled genome length was 122,115 bp (gaps included). Comparatively, the P. rubens chloroplast genome reported here may be considered a near-complete draft. Global genome alignment and phylogenetic analysis based on the whole chloroplast genome sequences of Picea rubens and 10 other Picea species revealed high sequence synteny and conservation among 11 Picea species and phylogenetic relationships consistent with their known classical interrelationships and published molecular phylogeny. The P. rubens chloroplast genome sequence showed the highest similarity with that of P. mariana and the lowest with that of P. sitchensis. We have annotated 107 genes including 69 protein-coding genes, 28 tRNAs, 4 rRNAs, few pseudogenes, identified 42 SSRs, and successfully designed primers for 26 SSRs. Mononucleotide A/T repeats were the most common followed by dinucleotide AT repeats. A similar pattern of microsatellite repeats occurrence was found in the chloroplast genomes of 11 Picea species.

The presence of a disease continuum in inflammatory arthritis (IA) is a recognised concept, with distinct stages from at-risk stage (presence of anti citrullinated-peptide autoantibody) to diagnosis of rheumatoid arthritis (RA), including therapy-induced remission. Despite T-cell dysregulation being a key feature of RA, there are few reports of T-cell phenotyping along the IA-continuum. We investigated the disturbances of naïve, regulatory and inflammation related cell (IRC) CD4+ T-cell subsets in 705 individuals across the IA-continuum, developing a simple risk-score (summing presence/absence of a risk-associated with a subset) to predict progression from one stage to the next. In 158 at-risk individuals, the 3 subsets had individual association with progression to IA and the risk-score was highly predictive (p

Objectives: To identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials. Methods: Phase II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from non-biological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the Disease Activity Score 28 (DAS28) at 6 months. Novel latent class mixed models characterised DAS28 over time. Results: IPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4%(95%CI 7.4%to9.5%) overall, 17%(95%CI 14.8%to19.4%) for MTX-naïve patients with early RA and 3.2% (95% CI 2.4% to 4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX reinitiation were associated with remission. In MTX-naïve patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory subpopulations were identified in MTX-naïve and MTX-exposed patients. A number of variables were associated with subpopulation membership and DAS28 levels within subpopulations. Conclusions: Predictors of remission differed between MTX-naïve and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biological therapy response, with three distinct trajectories observed in both MTX-naïve and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies.

The expression of mRNAs encoding the three GABAA receptor subunits that are associated with the most abundant benzodiazepine-sensitive GABAA receptor in adult cortex, that is, the α1, β2, and γ2 subunits, was studied in rat cortex during pre- and postnatal development by means of in situ. hybridization γ2 and β2 mRNAs become detectable in neocortex at gestational day 16 (GD16), α1, at GD18. γ2 mRNA exhibits the highest level of expression at early ages, while α1, mRNA levels are low. β2 mRNA rises steeply during the last days of gestation. Around birth, it shows the highest expression of the three subunits studied in cortex, and increases further until postnatal day 15 (PD15). The expression of α1, subunit mRNA also increases markedly shortly before birth and accelerates between PD8 and PD15, when it reaches higher levels than the other two subunits. Following the initial high expression, γ2 mRNA increases gradually and slowly until PD25. During prenatal development, highest expression of all three subunit mRNAs is found in the upper layers of cortex, that is, cortical plate and marginal zone. The subplate layer does not start to express GABAA receptor subunit mRNAs until GD18. At birth, all developing layers of the cortex express mRNAs for the three subunits, except the marginal zone. Highest levels are found in the upper part of the cortical plate. At the end of the first postnatal week (PD8), the laminar distribution of mRNA expression in neocortex becomes more differentiated. For all three subunit mRNAs, highest expression is then observed in neuron-like cells in layer IV in the granular areas, and over layers III and upper V in agranular areas. Subsequently, between PD8 and PD25, increasing levels of expression are observed over the pyramidal cell layer V. This regionally differentiated, developmental pattern suggests a close relationship between development of GABAA receptor subunits, ingrowth of thalamocortical projections, and maturation of neocortical circuitry