Strong microsite control of seedling recruitment in tundra

The inclusion of environmental variation in studies of recruitment is a prerequisite for realistic predictions of the responses of vegetation to a changing environment. We investigated how seedling recruitment is affected by seed availability and microsite quality along a steep environmental gradient in dry tundra. A survey of natural seed rain and seedling density in vegetation was combined with observations of the establishment of 14 species after sowing into intact or disturbed vegetation. Although seed rain density was closely correlated with natural seedling establishment, the experimental seed addition showed that the microsite environment was even more important. For all species, seedling emergence peaked at the productive end of the gradient, irrespective of the adult niches realized. Disturbance promoted recruitment at all positions along the environmental gradient, not just at high productivity. Early seedling emergence constituted the main temporal bottleneck in recruitment for all species. Surprisingly, winter mortality was highest at what appeared to be the most benign end of the gradient. The results highlight that seedling recruitment patterns are largely determined by the earliest stages in seedling emergence, which again are closely linked to microsite quality. A fuller understanding of microsite effects on recruitment with implications for plant community assembly and vegetation change is provided

Itch as major mediator of effect of tofacitinib on health-related quality of life in psoriatic arthritis: a mediation analysis

Patients with psoriatic arthritis (PsA) experience impaired health-related quality of life (HRQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA, which has been associated with improvements in dermatologic endpoints in patients with PsA. To assess the extent to which tofacitinib affects patient HRQoL via improvements in dermatologic symptoms, including itch, data were pooled from patients with PsA who received tofacitinib in phase III studies (NCT01866668 and NCT01882439). Mediation modeling assessed the indirect effects (via Itch Severity Item [ISI] and Physician’s Global Assessment of Psoriasis [PGA-PsO]) and direct effects (via all other factors) of tofacitinib treatment on dermatology-specific HRQoL (measured by Dermatology Life Quality Index [DLQI]). In the initial model, the treatment effect on DLQI was largely mediated by itch (ISI; p < 0.0001) and PGA-PsO (p < 0.01). The model was re-specified to assess the indirect effects only of itch and PGA-PsO on DLQI. Here, 17.7% of the treatment effect on DLQI was attributable to PGA-PsO (p = 0.0006), and 82.3% to itch (p < 0.0001). Tofacitinib-dependent improvements in DLQI were primarily mediated by itch relief, in addition to improvements in PGA-PsO

Itch as the major mediator of the effect of tofacitinib on health-related quality of life in PSA: a mediation analysis

Background: PsA is a chronic, systemic inflammatory disease with signs and symptoms across multiple domains, including cutaneous manifestations, which can impact health-related quality of life (HQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. In two Phase 3 randomised studies, patients (pts) with active PsA treated with tofacitinib experienced greater improvements in various dermatologic endpoints, compared with placebo. As pruritus is a bothersome symptom of skin disease in pts with PsA, we sought to determine how tofacitinib affects HQoL via clinical improvements in skin symptoms including itch. Objectives: To determine the relationships between tofacitinib treatment, dermatologic symptoms and pt-reported HQoL related to skin disease in PsA. Methods: Analyses used data (mean scores from Months 1 and 3) from two Phase 3 studies (OPAL Broaden [ NCT01877668 ]; OPAL Beyond [ NCT01882439 ]) of pts with active PsA treated with tofacitinib 5 mg twice daily or placebo; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response (IR) to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Mediation modelling, a statistical method used to assess mechanisms underlying observed relationships between different variables via other explanatory variables (mediators), was applied. The mediation model included: treatment, as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); HQoL, measured by Dermatology Life Quality Index (DLQI), as the dependent (outcome) variable; and two mediators, pt-reported Itch Severity Index (ISI) and Physician’s Global Assessment of Psoriasis (PGA-PsO) (a latent variable represented by erythema, induration and scaling). The initial model designated the treatment effect on DLQI mediated via ISI and PGA-PsO as an indirect effect, and treatment effects not attributable to ISI or PGA-PsO as a direct effect (Figure 1). Results: Data were collected from 468 pts, pooled from both studies. In the initial model (pooled data), the effect of tofacitinib treatment on DLQI was largely mediated by itch (measured by ISI) and PGA-PsO (indirect effect) (p<0.0001); the effect of treatment attributable to factors other than ISI and PGA-PsO (direct effect) was not statistically significant (p=0.66). Results were consistent for pooled and individual study data. Because the direct effect was small and not statistically significant, the model was re-specified to exclude the direct effect of tofacitinib treatment on DLQI. In the revised model (pooled data), 17.7% of the indirect effect was attributable to PGA-PsO (p=0.0006) and 82.3% was attributable to itch (assessed by ISI) (p<0.0001) (Figure 2). Analyses of individual studies using the revised model gave results generally consistent with pooled data. Conclusion: Dermatology-focused mediation modelling showed that a majority of the effect (~80%) of tofacitinib treatment on DLQI is mediated by improvements in itch, with ~20% mediated via improvements in PGA-PsO. Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Gil Yosipovitch Grant/research support from: Galderma, Kiniksa, Leo, Menlo, Novartis, Pfizer, Sanofi Regeneron, Consultant of: Eli Lilly, Galderma, Kiniksa, Leo, Menlo Therapeutics, Novartis, Pfizer Inc, Sanofi Regeneron, Trevi, Sienn

Relationships of dermatologic symptoms and quality of life in patients with psoriatic arthritis: analysis of two tofacitinib phase III studies

Objectives Evaluate relationships between changes in dermatologic assessments and quality of life (QoL) measures; quantify dermatologic symptom severity impacts on QoL in patients with psoriatic arthritis (PsA) treated with tofacitinib. Methods Data were from two phase III studies; patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg every other week, or placebo advancing to tofacitinib 5 or 10 mg BID at Month 3. Repeated measures longitudinal models assessed relationships between dermatologic assessments (predictors) Itch Severity Item (ISI), Physician’s Global Assessment of Psoriasis (PGA-PsO), and Patient’s Global Joint and Skin Assessment-Visual Analog Scale-Psoriasis question (PGJS-VAS-PsO), and QoL measures (outcomes) Dermatology Life Quality Index (DLQI) and Short Form-36 Health Survey Version 2 (SF-36v2). Models included one predictor and one outcome. Results Direct, approximately linear relationships existed between predictors and outcomes. ISI/PGA-PsO/PGJS-VAS-PsO improvements from baseline of ≥3/≥2/≥40-mm VAS corresponded with clinically meaningful DLQI improvements; improvements from baseline of ≥4/≥3/≥40-mm VAS generally corresponded with clinically meaningful improvements across component scores and all SF-36v2 domains. Conclusions Substantial links exist between dermatologic symptoms and QoL in patients with PsA, potentially informing patient-centered care and research. Rheumatologists should be aware of dermatologic manifestations and QoL impacts in patients with PsA. ClinicalTrials.gov NCT01877668; NCT0188243

Postpassivation of multication perovskite with rubidium butyrate

Many multication perovskites for highly stable and efficient solar cells benefit from rubidium iodide introduced in the precursor solution. It is well-known that Rb+ influences positively the optoelectronic and mobility properties and has a direct effect upon crystallization and halide homogenization. As Rb+ is often incorporated by adding RbI in the precursor solution, it can be difficult to distinguish the influence of Rb+ and I– separately. Herein, we report a postpassivation of methylammonium-free (CsFA) perovskite films with rubidium butyrate (RbBu). The passivation with RbBu increases the hydrophobicity of the perovskite surface and passivates shallow and deep traps, leading to an increase of charge-carrier lifetimes and diffusion lengths. Consequently, a better photovoltaic performance is also observed. These superior properties are attributed to both surface (halide-vacancy) and grain-boundary passivation by the carboxylate group and Rb+, respectively. We found that Rb+ itself acts as a direct and powerful passivating agent for multication perovskites, and this is proven by decoupling its contribution and halide’s contribution to other important performance parameters (e.g., crystallization, halide vacancies filling, etc.)