Cohomological finiteness conditions and centralisers in generalisations of Thompson's group V

We consider generalisations of Thompson's group $V$, denoted $V_r(\Sigma)$, which also include the groups of Higman, Stein and Brin. We show that, under some mild hypotheses, $V_r(\Sigma)$ is the full automorphism group of a Cantor-algebra. Under some further minor restrictions, we prove that these groups are of type $\mathrm{F}_\infty$ and that this implies that also centralisers of finite subgroups are of type $\mathrm{F}_\infty$.Comment: 19 pages, 2 figures. Revised version. The original submission has now been split into two papers. The current submission contains the first one. The second part is being reworked and will be reposted soon independently. Lemma 4.8 was incorrect as stated and has since been rectified. The results of the paper are unchange

Future targets in the management of systemic sclerosis

CTDs—such as SSc and SLE and related rheumatic diseases such as RA—have complex, underlying pathogeneses that include fibrosis, vascular dysfunction, activation of the immune system and inflammation. Although some current therapies for SSc offer benefits to patients, there is a clear need to investigate potential therapeutic targets. However, the breadth and diversity of cellular pathways and mediators implicated in these diseases, coupled with inherent redundancies in these systems, has made pre-clinical investigation difficult. Despite this, recent advances have been made in elucidating the immunological aspects of CTD, including the roles of B cells, T cells, matrix-remodelling cells and autoantibodies, enabling novel therapeutic approaches including immunoablation to be investigated. The mechanisms underlying the fibrosis that characterizes SSc are also becoming clearer; and as the putative events that trigger excessive collagen deposition are identified, so too are potential junctures at which these aberrant processes may be deactivated. Progress is also being made in understanding the vasculopathy in SSc, and the potential benefits of antioxidants and endothelin receptor antagonists. There have been some significant advances in the treatments available to SSc patients; however, this spectrum of diseases remains challenging, and continues in some cases to be associated with high morbidity, increased mortality and poor prognosi

Late-onset systemic sclerosis—a systematic survey of the EULAR scleroderma trials and research group database

Objective. The clinical course of SSc depends on subtype, organ involvement and age. Few data are reported on patients suffering from late-onset SSc. Methods. We analysed data from 8554 patients prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) group database. Late-onset SSc was defined as onset of non-RP disease features at or beyond 75 years of age. Disease characteristics, clinical features, disease course and mortality were evaluated. Results. A total of 123 patients with SSc onset at or beyond 75 years of age were identified. Compared with patients <75 years they had more frequently limited than diffuse SSc and a higher prevalence of anti-centromere autoantibodies. Fewer old patients had digital ulcers. The modified Rodnan's skin score, the prevalence of lung fibrosis and renal crisis did not differ significantly between groups. Pulmonary hypertension (PH) measured by echocardiography was more prevalent in the late-onset group, as well as arterial hypertension and diastolic dysfunction. Late-onset SSc remained a positive predictor for PH in multivariate analyses. No significant difference of the two groups in skin score or diffusion capacity was observed during follow-up. Mortality due to SSc was higher in the late-onset group, but the survival time from diagnosis was longer compared with the younger patients. Conclusion. Late-onset SSc shows a distinct clinical presentation and outcome. Patients with late-onset SSc suffer more frequently from the limited subtype and PH, but fewer patients have digital ulcers. PH may in part be determined by underlying cardiovascular diseas

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Value of systolic pulmonary arterial pressure as a prognostic factor of death in the systemic sclerosis EUSTAR population.

The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort.Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables.Based on our selection criteria, 1476 patients were included in the analysis; 87\% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31\% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of 50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95\% CI 1.035, 3.247) and HR 0.973 (95\% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95\% CI 1.91, 4.78) for sPAP ≥36 mmHg.An estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization

Smoking in Systemic Sclerosis: a Longitudinal European Scleroderma Trials and Research Group Study

Data on the role of tobacco exposure in systemic sclerosis (SSc) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations in the EUSTAR database