The molecular structure of melts along the carbonatite–kimberlite–basalt compositional joint: CO2and polymerisation

International audienceTransitional melts, intermediate in composition between silicate and carbonate melts, form by low degree partial melting of mantle peridotite and might be the most abundant type of melt in the asthenosphere. Their role in the transport of volatile elements and in metasomatic processes at the planetary scale might be significant yet they have remained largely unstudied. Their molecular structure has remained elusive in part because these melts are difficult to quench to glass. Here we use FTIR, Raman, 13C and 29Si NMR spectroscopy together with First Principle Molecular Dynamic (FPMD) simulations to investigate the molecular structure of transitional melts and in particular to assess the effect of CO2on their structure. We found that carbon in these glasses forms free ionic carbonate groups attracting cations away from their usual ‘depolymerising’ role in breaking up the covalent silicate network. Solution of CO2in these melts strongly modifies their structure resulting in a significant polymerisation of the aluminosilicate network with a decrease in NBO/Si of about 0.2 for every 5 mol% CO2dissolved.This polymerisation effect is expected to influence the physical and transport properties of transitional melts. An increase in viscosity is expected with increasing CO2content, potentially leading to melt ponding at certain levels in the mantle such as at the lithosphere–asthenosphere boundary. Conversely an ascending and degassing transitional melt such as a kimberlite would become increasingly fluid during ascent hence potentially accelerate. Carbon-rich transitional melts are effectively composed of two sub-networks:a carbonate and a silicate one leading to peculiar physical and transport properties

Characteristics and outcomes of patients treated with apremilast in the real world: results from the APPRECIATE study

Background APPRECIATE is a multinational, observational, retrospective, cross‐sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor. Objectives To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real‐world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes. Methods In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires. Results In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6–13.4) and 13.4 (13.0; 11.4–14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5–6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians’ perspective on overall success of apremilast in meeting expectations correlated with patients’ perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache. Conclusions Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real‐world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation

Secukinumab demonstrated sustained retention, effectiveness and safety in a real-world setting in patients with moderate-to-severe plaque psoriasis: long-term results from an interim analysis of the SERENA study.

Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease. To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO). SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years. In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m <sup>2</sup> were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed. Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA

From compact to fractal crystalline clusters in concentrated systems of monodisperse hard spheres

We address the crystallization of monodisperse hard spheres in terms of the properties of finite- size crystalline clusters. By means of large scale event-driven Molecular Dynamics simulations, we study systems at different packing fractions {\phi} ranging from weakly supersaturated state points to glassy ones, covering different nucleation regimes. We find that such regimes also result in different properties of the crystalline clusters: compact clusters are formed in the classical-nucleation-theory regime ({\phi} \leq 0.54), while a crossover to fractal, ramified clusters is encountered upon increasing packing fraction ({\phi} \geq 0.56), where nucleation is more spinodal-like. We draw an analogy between macroscopic crystallization of our clusters and percolation of attractive systems to provide ideas on how the packing fraction influences the final structure of the macroscopic crystals. In our previous work (Phys. Rev. Lett., 106, 215701, 2011), we have demonstrated how crystallization from a glass (at {\phi} > 0.58) happens via a gradual (many-step) mechanism: in this paper we show how the mechanism of gradual growth seems to hold also in super-saturated systems just above freezing showing that static properties of clusters are not much affected by dynamics.Comment: Soft Matter, 201

Gabapentin for the Management of Chronic Pelvic Pain in Women (GaPP1): A Pilot Randomised Controlled Trial

Chronic pelvic pain (CPP) affects 2.1–24% of women. Frequently, no underlying pathology is identified, and the pain is difficult to manage. Gabapentin is prescribed for CPP despite no robust evidence of efficacy. We performed a pilot trial in two UK centres to inform the planning of a future multicentre RCT to evaluate gabapentin in CPP management. Our primary objective was to determine levels of participant recruitment and retention. Secondary objectives included estimating potential effectiveness, acceptability to participants of trial methodology, and cost-effectiveness of gabapentin. Women with CPP and no obvious pelvic pathology were assigned to an increasing regimen of gabapentin (300-2700mg daily) or placebo. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to six months. The analyses by treatment group were by intention-to-treat. Interviews were conducted to evaluate women’s experiences of the trial. A probabilistic decision analytical model was used to estimate cost-effectiveness. Between September 2012–2013, 47 women (34% of those eligible) were randomised (22 to gabapentin, 25 to placebo), and 25 (53%) completed six-month follow-up. Participants on gabapentin had less pain (BPI difference 1.72 points, 95% CI:0.07–3.36), and an improvement in mood (HADS difference 4.35 points, 95% CI:1.97–6.73) at six months than those allocated placebo. The majority of participants described their trial experience favorably. At the UK threshold for willingness-to-pay, the probabilities of gabapentin or no treatment being cost-effective are similar. A pilot trial assessing gabapentin for CPP was feasible, but uncertainty remains, highlighting the need for a large definitive trial

Gibbs' Paradox according to Gibbs and slightly beyond

The so-called Gibbs paradox is a paradigmatic narrative illustrating the necessity to account for the N! ways of permuting N identical particles when summing over microstates. Yet, there exist some mixing scenarios for which the expected thermodynamic outcome depends on the viewpoint one chooses to justify this combinatorial term. After a brief summary on Gibbs' paradox and what is the standard rationale used to justify its resolution, we will allow ourself to question from a historical standpoint whether the Gibbs paradox has actually anything to do with Gibbs' work. In so doing, we also aim at shedding a new light with regards to some of the theoretical claims surrounding its resolution. We will then turn to the statistical thermodynamics of discrete and continuous mixtures and introduce the notion of composition entropy to characterise these systems. This will enable us to address, in a certain sense, a "curiosity" pointed out by Gibbs in a paper published in 1876. Finally, we will �nish by proposing a connexion between the results we propose and a recent extension of the Landauer bound regarding the minimum amount of heat to be dissipated to reset one bit of memory

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris – : Part 1: treatment and monitoring recommendations

Peer reviewe

Exercise and manual auricular acupuncture: a pilot assessor-blind randomised controlled trial. (The acupuncture and personalised exercise programme (APEP) Trial)

<p>Abstract</p> <p>Background</p> <p>Evidence supports the use of exercise for chronic low back pain (CLBP); however, adherence is often poor due to ongoing pain. Auricular acupuncture is a form of pain relief involving the stimulation of points on the outer ear corresponding with specific body parts. It may be a useful adjunct to exercise in managing CLBP; however, there is only limited evidence to support its use with this patient group.</p> <p>Methods/Design</p> <p>This study was designed to test the feasibility of an assessor-blind randomised controlled trial which assess the effects on clinical outcomes and exercise adherence of adding manual auricular acupuncture to a personalised and supervised exercise programme (PEP) for CLBP. No sample size calculation has been carried out as this study aims to identify CLBP referral rates within the catchment area of the study site. The researchers aim to recruit four cohorts of n = 20 participants to facilitate a power analysis for a future randomised controlled trial. A computer generated random allocation sequence will be prepared centrally and used to allocate participants by cohort to one of the following interventions: 1) six weeks of PEP <it>plus </it>manual auricular acupuncture; 2) six weeks of PEP alone. Both groups will also complete a further six weeks of self-paced exercise with telephone follow-up support. In addition to a baseline and exit questionnaire at the beginning and end of the study, the following outcomes will be collected at baseline, and after 7, 13 and 25 weeks: pain frequency and bothersomeness, back-specific function, objective assessment and recall of physical activity, use of analgesia, perceived self-efficacy, fear avoidance beliefs, and beliefs about the consequences of back pain. Since this is a feasibility study, significance tests will not be presented, and treatment effects will be represented by point estimates and confidence intervals. For each outcome variable, analysis of covariance will be performed on the data, conditioning on the baseline value.</p> <p>Discussion</p> <p>The results of this study investigating the adjuvant effects of auricular acupuncture to exercise in managing CLBP will be used to inform the design of a future multi-centre randomised controlled trial.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN94142364.</p

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2 : specific clinical and comorbid situations

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.Peer reviewe