The use of scenarios and models to evaluate the future of nature values and ecosystem services in Mediterranean forests

Science and society are increasingly interested in predicting the effects of global change and socio-economic development on natural systems, to ensure maintenance of both ecosystems and human well-being. The Intergovernmental Platform on Biodiversity and Ecosystem Services has identified the combination of ecological modelling and scenario forecasting as key to improving our understanding of those effects, by evaluating the relationships and feedbacks between direct and indirect drivers of change, biodiversity, and ecosystem services. Using as case study the forests of the Mediterranean basin (complex socio-ecological systems of high social and conservation value), we reviewed the literature to assess (1) what are the modelling approaches most commonly used to predict the condition and trends of biodiversity and ecosystem services under future scenarios of global change, (2) what are the drivers of change considered in future scenarios and at what scales, and (3) what are the nature and ecosystem service indicators most commonly evaluated. Our review shows that forecasting studies make relatively little use of modelling approaches accounting for actual ecological processes and feedbacks between different socio-ecological sectors; predictions are generally made on the basis of a single (mainly climate) or a few drivers of change. In general, there is a bias in the set of nature and ecosystem service indicators assessed. In particular, cultural services and human well-being are greatly underrepresented in the literature. We argue that these shortfalls hamper our capacity to make the best use of predictive tools to inform decision-making in the context of global change.This work was supported by the Spanish Government through the INMODES project (grant number CGL2017-89999-C2-2-R), the ERA-NET FORESTERRA project INFORMED (grant number 29183), and the project Boscos Sans per a una Societat Saludable funded by Obra Social la Caixa (https://obrasociallacaixa.org/). AMO and AA were supported by Spanish Government through the “Juan de la Cierva” fellowship program (IJCI-2016-30349 and IJCI-2016-30049, respectively). JVRD was supported by the Government of Asturias and the FP7-Marie Curie-COFUND program of the European Commission (Grant “Clarín” ACA17-02)

Cytokine correlates of clinical response patterns to infliximab treatment of ankylosing spondylitis

Methods: Baseline and sequential cytokine levels (IL1, TNFα, IFNγ, TGFß and IL10) were examined after 52 weeks of infliximab treatment 5 mg/kg in 22 patients. Results: At week 52, 18 patients were responders and four non-responders according to ASAS group criteria. Clinical measures of disease activity between the two groups at baseline were similar, apart from a trend towards longer disease duration in non-responders (p = 0.08). Baseline CRP and TNFα levels were higher in responders than non-responders (p<0.01 and p<0.006, respectively). The two groups had similar baseline cytokine levels, apart from TNFα. Baseline CRP levels did not correlate significantly with baseline cytokine levels in responders, but a strong correlation was noted between baseline CRP and IL1, IFNγ, and IL10 in non-responders. Apart from an early rise in TGFß and a decrease in IL10 in responders after the first infusion, sequential cytokine analysis for the first six months of treatment was not related to clinical disease activity measures. Conclusion: Although sequential cytokine analysis does not appear to be informative, baseline CRP and TNFα levels are useful markers of clinical response patterns in patients with AS treated with infliximab

Relationship between disease activity and infection in patients with spondyloarthropathies

Methods: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by χ(2) or Fisher's tests. Results: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in ∼50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. Conclusion: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA

VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis

ObjectiveTo assess the efficacy and safety of decernotinib (VX-509), an oral selective inhibitor of JAK-3, in patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate. MethodsIn this 24-week, double-blind, randomized phase IIb study, 358 patients with active RA received either placebo (n=71) or VX-509 at dosages of 100 mg/day (n=71), 150 mg/day (n=72), 200 mg/day (n=72), or 100 mg twice daily (n=72). Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and change from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). ResultsAt week 12, the ACR20 response rates were 46.5%, 66.7%, 56.9%, and 68.1% in the groups receiving VX-509 at dosages of 100 mg/day, 150 mg/day, 200 mg/day, and 100 mg twice daily, respectively, and 18.3% in the placebo group (P <0.001 for all comparisons). At week 12, the mean change from baseline in the DAS28-CRP was significantly greater in each VX-509 group compared with the placebo group (P <0.001). Improvements were maintained at week 24, as shown by the ACR20, ACR50, and ACR70 response rates and mean change from baseline in the DAS28-CRP. The most common adverse event in the VX-509 group was headache (8.7%), and elevated levels of transaminases, lipoproteins, and creatinine were observed. ConclusionVX-509 significantly improved the signs and symptoms of RA at weeks 12 and 24 compared with the placebo group when it was administered in combination with methotrexate. Safety signals included infection and increases in liver transaminase and lipid level

Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients

Objective: To investigate the role of HLA-B and HLA-DR genes as contributors to genetic susceptibility and clinical expression of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 172 patients with SpA (undifferentiated SpA 83, ankylosing spondylitis (AS) 64, and reactive arthritis 25) and 99 healthy controls. The HLA-B and HLA-DR alleles were detected by the polymerase chain reaction with sequence-specific primers technique. Patient assessment included demographic data, diagnostic categories, and disease patterns. Statistical methods included the Mantel-Haenzel χ(2) test, Fisher's exact test, and Woolf method for odds ratio (OR). Differences of continuous variables between HLA allele groups were calculated by Student's t test. Results: Increased frequencies of HLA-B27 (pCh10(-3), OR=28.7), HLA-DR1 (pC=0.045, OR=2.77), and HLA-B15 (p=0.034, pC=NS, OR=2.04) alleles in the whole group were found. HLA-B27 strength of association (OR) was 41.4 in AS; 20.9 in undifferentiated SpA; 27.2 in reactive arthritis. HLA-DR1 and HLA-B15 were increased in undifferentiated SpA (pC=0.045, OR=2.98 and p=0.004, pC=NS, OR=2.75). By analysing 58 HLA-B27 negative patients it was found that HLA-B15 and HLA-DR1 associations with SpA were independent of HLA-B27; increased frequencies of HLA-B15 were found in the whole SpA group and in patients with undifferentiated SpA (pC=0.03, OR=3.09 and pCh0.01, OR=3.77) and of HLA-DR1 in the latter (p=0.04, pC=NS, OR=3.15). HLA-B27 positive patients were younger than HLA-B27 negative patients at onset (p=0.03), but HLA-DR1 positive patients were older than HLA-DR1 negative patients (p=0.03). Bath indices for disease activity and functioning were higher in HLA-B27 positive patients (p=0.006 and p=0.004 v HLA-B27 negative patients). In contrast, neither HLA-DR1 nor HLA-B15 influenced these indices. Conclusion: Apart from HLA-B27, there is a significant association of HLA-DR1 and HLA-B15 with SpA in Mexicans which is independent of B27. HLA-B27 is associated with younger age at onset and increased disease severity and HLA-DR1 with older age at onset. The strength of HLA-B15, HLA-B27, and HLA-DR1 associations varied in different forms of SpA

Heat shock protein 70 gene polymorphisms in Mexican patients with spondyloarthropathies

Objective: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. Methods: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, χ(2), Fisher's exact test, and Woolf's method for odds ratio (OR). Results: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC<0.05, OR=4.3), as well as in the different clinical subgroups (pC<0.05, OR=4.2 for AS; pC<0.05, OR=4.4 for uSpA; and pC<0.05, OR=4.1 for ReA). This frequency remained significantly increased when the patients with B27 negative SpA were analysed. On the other hand, HSP70-hom locus analysis showed significantly increased frequency of A allele in the whole group of SpA (pC<0.05, OR=3.4), as well as in the groups with AS (pC<0.05, OR=5.6) and with uSpA (pC<0.05, OR=3.1), when compared with healthy controls. In this case, also, the genotype A/A was increased in the whole group of SpA (pC<0.05, OR=4.5), as well as in patients with AS (pC<0.05, OR=6.4) and with uSpA (pC<0.05, OR=3.7). When the patients with B27 negative SpA were analysed the frequencies of HSP70-hom A allele and A/A genotype remained significantly increased in the whole group of SpA (pC<0.05, OR=3.2 for the A allele and pC<0.05, OR=4.2 for the A/A genotype) and in the uSpA subgroup (pC<0.05, OR=3.8 for the A allele and pC<0.05, OR=4.3 for the A/A genotype). Conclusion: In addition to the association of SpA with HLA-B27, there is a significant association of HSP70-2 and HSP70-hom alleles with SpA in Mexicans. This association seems to be independent of the susceptibility conferred by HLA-B27 in the group of patients with uSpA

Development of a radiographic index to assess the tarsal involvement in patients with spondyloarthropathies

Objective: To develop and test an index to evaluate the radiographic changes that occur in the tarsus and adjacent areas of the foot in patients with spondyloarthropathies (SpA). Methods: The spondyloarthropathy tarsal radiographic index (SpA-TRI) was developed in three consecutive steps: (a) detection of descriptors after reviewing 70 radiographic files; (b) descriptor gradation and subsequent modifications performed by a consensus committee, and (c) interobserver variability assessed by three blinded and independent observers on 272 radiographs: anteroposterior 118, lateral 90, oblique 64 from 121 patients with SpA, and intraobserver variability on 75 radiographs from 25 patients with SpA. Statistical analysis included percentage of agreement and κ test. SpA-TRI score ranges from 0 to 4 (0=normal; 1=osteopenia or suspicious findings; 2=definite joint space narrowing, bony erosion(s), periosteal whiskering, or enthesophyte(s) in the plantar fascia or Achilleal tendon attachments; 3=para-articular enthesophyte(s); 4=bony ankylosis (joint space fusion or complete bridging)). Results: Complete agreement for every evaluation was >40%, and discordance >1 grade was <15%. The κ scores among the three observers were acceptable for all the single projections: oblique (0.52, 0.36, 0.35), lateral (0.50, 0.42, 0.56), and anteroposterior (0.40, 0.41, 0.21) views. The combination of lateral and oblique views achieved the highest concordance rates (0.72, 0.33, 0.66), surpassing that of the three projections altogether (0.34, 0.58, 0.37). In every case the concordance was comparable with that of sacroiliac joints (0.47, 0.41, 0.34); intraobserver concordance showed a similar trend. Conclusion: The SpA-TRI is an index that includes the most prominent features of tarsal disease and adjacent areas of the foot in SpA and grades them accordingly, it has an adequate reproducibility, and is suitable for use with two or more projections, preferably the combination of oblique and lateral