Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trial.

BACKGROUND: Atopic eczema (AE) is a common skin problem that impairs quality of life and is associated with the development of other atopic diseases including asthma, food allergy and allergic rhinitis. AE treatment is a significant cost burden for health care providers. The purpose of the trial is to investigate whether daily application of emollients for the first year of life can prevent AE developing in high-risk infants (first-degree relative with asthma, AE or allergic rhinitis). METHODS: This is a protocol for a pragmatic, two-arm, randomised controlled, multicentre trial. Up to 1400 term infants at high risk of developing AE will be recruited through the community, primary and secondary care in England. Participating families will be randomised in a 1:1 ratio to receive general infant skin-care advice, or general skin-care advice plus emollients with advice to apply daily to the infant for the first year of life. Families will not be blinded to treatment allocation. The primary outcome will be a blinded assessment of AE at 24 months of age using the UK Working Party Diagnostic Criteria for Atopic Eczema. Secondary outcomes are other definitions of AE, time to AE onset, severity of AE (EASI and POEM), presence of other allergic diseases including food allergy, asthma and hay fever, allergic sensitisation, quality of life, cost-effectiveness and safety of the emollients. Subgroup analyses are planned for the primary outcome according to filaggrin genotype and the number of first-degree relatives with AE and other atopic diseases. Families will be followed up by online and postal questionnaire at 3, 6, 12 and 18 months with a face-to-face visit at 24 months. Long-term follow-up until 60 months will be via annual questionnaires. DISCUSSION: This trial will demonstrate whether skin-barrier enhancement through daily emollient for the first year of life can prevent AE from developing in high-risk infants. If effective, this simple and cheap intervention has the potential to result in significant cost savings for health care providers throughout the world by preventing AE and possibly other associated allergic diseases. TRIAL REGISTRATION: ISRCTN registry; ID: ISRCTN21528841 . Registered on 25 July 2014

A system of ODEs for a Perturbation of a Minimal Mass Soliton

We study soliton solutions to a nonlinear Schrodinger equation with a saturated nonlinearity. Such nonlinearities are known to possess minimal mass soliton solutions. We consider a small perturbation of a minimal mass soliton, and identify a system of ODEs similar to those from Comech and Pelinovsky (2003), which model the behavior of the perturbation for short times. We then provide numerical evidence that under this system of ODEs there are two possible dynamical outcomes, which is in accord with the conclusions of Pelinovsky, Afanasjev, and Kivshar (1996). For initial data which supports a soliton structure, a generic initial perturbation oscillates around the stable family of solitons. For initial data which is expected to disperse, the finite dimensional dynamics follow the unstable portion of the soliton curve.Comment: Minor edit

Coexistence of 'alpha+ 208Pb' cluster structures and single-particle excitations in 212Po

Excited states in 212Po have been populated by alpha transfer using the 208Pb(18O,14C) reaction at 85MeV beam energy and studied with the EUROBALL IV gamma multidetector array. The level scheme has been extended up to ~ 3.2 MeV excitation energy from the triple gamma coincidence data. Spin and parity values of most of the observed states have been assigned from the gamma angular distributions and gamma -gamma angular correlations. Several gamma lines with E(gamma) < 1 MeV have been found to be shifted by the Doppler effect, allowing for the measurements of the associated lifetimes by the DSAM method. The values, found in the range [0.1-0.6] ps, lead to very enhanced E1 transitions. All the emitting states, which have non-natural parity values, are discussed in terms of alpha-208Pb structure. They are in the same excitation-energy range as the states issued from shell-model configurations.Comment: 21 pages, 19 figures, corrected typos, revised arguments in Sect. III

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

BACKGROUND Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. METHODS In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. RESULTS We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. CONCLUSIONS In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743; SOLO 2 ClinicalTrials .gov number, NCT02277769.

Spallation reactions. A successful interplay between modeling and applications

The spallation reactions are a type of nuclear reaction which occur in space by interaction of the cosmic rays with interstellar bodies. The first spallation reactions induced with an accelerator took place in 1947 at the Berkeley cyclotron (University of California) with 200 MeV deuterons and 400 MeV alpha beams. They highlighted the multiple emission of neutrons and charged particles and the production of a large number of residual nuclei far different from the target nuclei. The same year R. Serber describes the reaction in two steps: a first and fast one with high-energy particle emission leading to an excited remnant nucleus, and a second one, much slower, the de-excitation of the remnant. In 2010 IAEA organized a worskhop to present the results of the most widely used spallation codes within a benchmark of spallation models. If one of the goals was to understand the deficiencies, if any, in each code, one remarkable outcome points out the overall high-quality level of some models and so the great improvements achieved since Serber. Particle transport codes can then rely on such spallation models to treat the reactions between a light particle and an atomic nucleus with energies spanning from few tens of MeV up to some GeV. An overview of the spallation reactions modeling is presented in order to point out the incomparable contribution of models based on basic physics to numerous applications where such reactions occur. Validations or benchmarks, which are necessary steps in the improvement process, are also addressed, as well as the potential future domains of development. Spallation reactions modeling is a representative case of continuous studies aiming at understanding a reaction mechanism and which end up in a powerful tool.Comment: 59 pages, 54 figures, Revie

Effectiveness of psychosocial interventions for adults with substance use disorder that have a co‐occurring common mental health disorder: an umbrella review

Issues People with substance use disorders can have co-occurring mental disorders. Approach An umbrella review was conducted to identify evidence of the effectiveness of psychosocial interventions for adults (aged 18+) with substance use disorders and co-occurring common mental health disorders. Systematic reviews were sought of randomised controlled trials of psychosocial interventions compared to each other, treatment as usual or wait-list. Five databases were systematically searched in February 2024. Data, including critical appraisal (Joanna Briggs Institute Checklist), were extracted by one reviewer and checked by another. Data were discussed in a narrative review. Key Findings Of 5420 unique records, 28 systematic reviews were included. The methodological quality of the reviews was good. Most reviews focused on depression, anxiety or post-traumatic stress disorder. There was much heterogeneity between reviews, and randomised controlled trials within reviews. Most of the interventions and many of the treatment-as-usual comparators resulted in significant improvement in substance use and mental health disorders. Results suggested integrated (co-ordinated) treatment for co-occurring diagnosis patients was better than treating one condition alone, and usually better than parallel uncoordinated services. There was limited evidence assessing sequential treatment, but this suggested similar effectiveness to integrated treatment. Implications Implications for current practise could not be recommended due to heterogeneity. Improvement shown by all types of psychosocial intervention including active comparators precluded recommending one type of intervention over another. Conclusion Further research is needed comparing integrated with parallel or sequential treatment, with follow-up of 6 months or longer, and sample size large enough to encompass dropout

Epidemiology of atopic dermatitis in adults: Results from an international survey.

Background:There are gaps in our knowledge of the prevalence of adult atopicdermatitis (AD).Objective:To estimate the prevalence of AD in adults and by disease severity.Methods:This international, cross-sectional, web-based survey was performed inthe United States, Canada, France, Germany, Italy, Spain, United Kingdom, andJapan. Adult members of online respondent panels were sent a questionnaire forAD identification and severity assessment; demographic quotas ensured populationrepresentativeness for each country. A diagnosis of AD required subjects to be posi-tive on the modified UK Working Party/ISAAC criteriaandself-report of ever hav-ing an AD diagnosis by a physician. The proportion of subjects with AD whoreported being treated for their condition was determined and also used to estimateprevalence. Severity scales were Patient-Oriented SCORAD, Patient-OrientatedEczema Measure, and Patient Global Assessment.Results:Among participants by region, the point prevalence of adult AD in the over-all/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% inthe EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vsfemales, and decreased with age. Regional variability was observed within countries.Severity varied by scale and region; however, regardless of the scale or region, propor-tion of subjects reporting severe disease was lower than mild or moderate disease.Conclusions:Prevalence of adult AD ranged from 2.1% to 4.9% across countries.Severe AD represented a small proportion of the overall AD population regardlessof measure or region

Standardized reporting of the Eczema Area and Severity Index (EASI) and the Patient-Oriented Eczema Measure (POEM): a recommendation by the Harmonising Outcome Measures for Eczema (HOME) Initiative

Several organizations from multiple fields of medicine are setting standards for clinical research including protocol development,1 harmonization of outcome reporting,2 statistical analysis,3 quality assessment4 and reporting of findings.1 Clinical research standardization facilitates the interpretation and synthesis of data, increases the usability of trial results for guideline groups and shared decision‐making, and reduces selective outcome reporting bias. The mission of the Harmonising Outcome Measures for Eczema (HOME) initiative is to establish an agreed‐upon core set of outcomes to be measured and reported in all clinical trials of atopic dermatitis (AD)