Consistent massive truncations of IIB supergravity on Sasaki-Einstein manifolds

Recent work on holographic superconductivity and gravitational duals of systems with non-relativistic conformal symmetry have made use of consistent truncations of D=10 and D=11 supergravity retaining some massive modes in the Kaluza-Klein tower. In this paper we focus on reductions of IIB supergravity to five dimensions on a Sasaki-Einstein manifold, and extend these previous truncations to encompass the entire bosonic sector of gauged D=5, N=2 supergravity coupled to massive multiplets up to the second Kaluza-Klein level. We conjecture that a necessary condition for the consistency of massive truncations is to only retain the lowest modes in the massive trajectories of the Kaluza-Klein mode decomposition of the original fields. This is an extension of the well-known result that consistent truncations may be obtained by restricting to the singlet sector of the internal symmetry group.Comment: 27 pages, typos corrected and references adde

The New Insight into the Role of Antimicrobial Proteins-Alarmins in the Immunopathogenesis of Psoriasis

The pathognesis of psoriasis still remains not fully elucidated. Recent advances favor the idea that interactions between innate and adaptive immune response drive inflammatory process in this disease. Innate antimicrobial peptides and proteins (AMPs) are diverse group of small molecules that provide the first line of defense against invading pathogens. In recent years, the novel functions ofAMPs have been identified. There are three subclasses among AMPs that have gained the special interest as a potentially important player in the pathogenesis of psoriasis: cathelicidin, S100 proteins, and defensins. These AMPs have been shown to modulate and trigger host immune response in psoriasis acting as interplayer between innate and adaptive immune mechanisms. Overexpressed in psoriatic lesions, they prime immune cells for enhanced production of proinflammatory mediators and act as chemoattractant for leukocytes. Therefore, the novel term describing AMPs alarmins has been suggested. As multifunctional player in pathogenesis of psoriasis, AMPs may constitute potential target for therapeutic interventions. However, further investigations are required to establish the methods of downregulation of the aberrant proinflammatory functions of AMPs without increasing the risk of infections

Identification and differentiation of Trichophyton rubrum clinical isolates using PCR-RFLP and RAPD methods

Trichophyton rubrum represents the most frequently isolated causative agent of superficial dermatophyte infections. Several genotyping methods have recently been introduced to improve the delineation between pathogenic fungi at both the species and the strain levels. The purpose of this study was to apply selected DNA fingerprinting methods to the identification and strain discrimination of T. rubrum clinical isolates. Fifty-seven isolates from as many tinea patients were subjected to species identification by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis and strain differentiation using a randomly amplified polymorphic DNA (RAPD) method, with two primers designated 1 and 6. Using PCR-RFLP, 55 of the isolates studied were confirmed to be T. rubrum. Among those, a total of 40 and five distinct profiles were obtained by RAPD with primers 1 and 6, respectively. The combination of profiles from both RAPD assays resulted in 47 genotypes and an overall genotypic diversity rate of 85.4%. A dendrogram analysis performed on the profiles generated by RAPD with primer 1 showed most of the isolates (87.3%) to be genetically related. PCR-RFLP serves as a rapid and reliable method for the identification of T. rubrum species, while the RAPD analysis is rather a disadvantageous tool for T. rubrum strain typing

Quantum computation with devices whose contents are never read

In classical computation, a "write-only memory" (WOM) is little more than an oxymoron, and the addition of WOM to a (deterministic or probabilistic) classical computer brings no advantage. We prove that quantum computers that are augmented with WOM can solve problems that neither a classical computer with WOM nor a quantum computer without WOM can solve, when all other resource bounds are equal. We focus on realtime quantum finite automata, and examine the increase in their power effected by the addition of WOMs with different access modes and capacities. Some problems that are unsolvable by two-way probabilistic Turing machines using sublogarithmic amounts of read/write memory are shown to be solvable by these enhanced automata.Comment: 32 pages, a preliminary version of this work was presented in the 9th International Conference on Unconventional Computation (UC2010

287 Effects of ruxolitinib cream on pruritus in black patients with atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease that has phenotypic differences across race and can be more severe in Black patients. In two phase 3 identical design studies (TRuE-AD1/TRuE-AD2), patients (≥12 years old with AD for ≥2 years, Investigator’s Global Assessment [IGA] score 2/3, 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (Janus kinase [JAK]1/JAK 2 inhibitor) cream or vehicle for 8 weeks. Here we describe the effect of ruxolitinib cream on itch in Black patients using pooled data from the 2 studies (n=292). Mean itch numerical rating scale (NRS) score at baseline was 5.3/5.4 for ruxolitinib cream (0.75%/1.5%) and 5.7 for vehicle. Reductions in mean itch NRS score with ruxolitinib cream (0.75%/1.5%) were evident within approximately 12 hours of first application (–0.6/–0.7 vs −0.2 for vehicle), with statistically significant reductions by Day 4 vs vehicle (–1.4/–1.6 vs –0.6; both P\u3c0.05). For those with baseline itch NRS ≥4 (n=187; 64.0%), more patients achieved ≥4-point itch NRS improvement vs vehicle by Day 2 (6.1%/16.4% vs 0%); this increased to 15.9%/26.6% vs 3.0% on Day 7 and 30.1%/43.2% vs 17.5% at Week 8 (P=0.212/P=0.009). More patients applying 0.75%/1.5% ruxolitinib cream vs vehicle reported no days of itch per question 1 of the Patient-Oriented Eczema Measure (POEM) at Week 2 (19.0%/19.4% vs 5.3%); this increased at Week 8 (34.0%/30.8% vs 12.2%). In summary, ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black patients with AD

Impairment of Sexual Life in 3,485 Dermatological Outpatients From a Multicentre Study in 13 European Countries

Skin conditions may have a strong impact on patients' sexual life, and thus influence personal relationships. Sexual issues are difficult to discuss directly in clinical practice, and a mediated instrument may be useful to capture such information. In this study item 9 of the Dermatology Life Quality Index was used to collect information on sexual impact of several skin conditions in 13 European countries. Among 3,485 patients, 23.1% reported sexual problems. The impairment was particularly high in patients with hidradenitis suppurativa, prurigo, blistering disorders, psoriasis, urticaria, eczema, infections of the skin, or pruritus. Sexual impact was strongly associated with depression, anxiety, and suicidal ideation. It was generally more frequent in younger patients and was positively correlated with clinical severity and itch. It is important to address the issue of sexual well-being in the evaluation of patients with skin conditions, since it is often linked to anxiety, depression, and even suicidal ideation.Peer reviewedFinal Published versio

Probing the accelerating Universe with radio weak lensing in the JVLA Sky Survey

We outline the prospects for performing pioneering radio weak gravitational lensing analyses using observations from a potential forthcoming JVLA Sky Survey program. A large-scale survey with the JVLA can offer interesting and unique opportunities for performing weak lensing studies in the radio band, a field which has until now been the preserve of optical telescopes. In particular, the JVLA has the capacity for large, deep radio surveys with relatively high angular resolution, which are the key characteristics required for a successful weak lensing study. We highlight the potential advantages and unique aspects of performing weak lensing in the radio band. In particular, the inclusion of continuum polarisation information can greatly reduce noise in weak lensing reconstructions and can also remove the effects of intrinsic galaxy alignments, the key astrophysical systematic effect that limits weak lensing at all wavelengths. We identify a VLASS "deep fields" program (total area ~10-20 square degs), to be conducted at L-band and with high-resolution (A-array configuration), as the optimal survey strategy from the point of view of weak lensing science. Such a survey will build on the unique strengths of the JVLA and will remain unsurpassed in terms of its combination of resolution and sensitivity until the advent of the Square Kilometre Array. We identify the best fields on the JVLA-accessible sky from the point of view of overlapping with existing deep optical and near infra-red data which will provide crucial redshift information and facilitate a host of additional compelling multi-wavelength science.Comment: Submitted in response to NRAO's recent call for community white papers on the VLA Sky Survey (VLASS

Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa:The SHARPS Randomized Clinical Trial

IMPORTANCE: Surgery is a mainstay in the management of hidradenitis suppurativa (HS). Adalimumab is the first drug approved for HS. OBJECTIVE: To investigate the efficacy and safety of adalimumab in combination with wide-excision surgery followed by secondary intention healing. DESIGN, SETTING, AND PARTICIPANTS: The Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically (SHARPS) trial was a phase 4, randomized, double-blind, placebo-controlled study of adalimumab in conjunction with surgery. Patients were enrolled in 45 sites across 20 countries from July 18, 2016, to February 2, 2019, with the last patient visit on October 16, 2019. Eligible patients (aged 18-65 years) had moderate to severe HS that required radical surgery in an axillary or inguinal region and had 2 other anatomical regions affected, with 1 or more regions at Hurley stage II or III. Analysis was conducted in November 2019. INTERVENTIONS: Patients were randomized 1:1 to receive continuous adalimumab, 40 mg, or placebo during presurgery (12 weeks), perioperative (2 weeks), and postoperative (10 weeks) periods. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients achieving HS clinical response across all body regions at week 12. RESULTS: Overall, 103 patients were randomized to adalimumab and 103 to matching placebo. Among all patients, 51% (n = 106) were women, 94% (n = 193) were White, and the mean (SD) age was 37.6 (11.3) years. At week 12, significantly more patients receiving adalimumab (49 of 103 [48%]) vs placebo (35 of 103 [34%]; P = .049) achieved HS clinical response across all body regions (treatment difference, 14% [95% CI, 0%-27%]). Treatment-emergent adverse events were reported in 74 of 103 patients (72%) and 69 of 103 patients (67%) in the adalimumab and placebo groups, respectively. No increased risk of postoperative wound infection, complication, or hemorrhage was observed with adalimumab vs placebo. Two deaths occurred in the adalimumab group; neither was considered as having a reasonable possibility of relationship to study drug. CONCLUSIONS AND RELEVANCE: Adalimumab was efficacious in conjunction with wide-excision surgery followed by secondary intention healing, with no need to interrupt treatment prior to surgery. These data support further investigation of adalimumab as an adjuvant therapy to surgery in patients with moderate to severe HS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0280897

A survey among dermatologists: diagnostics of superficial fungal infections - what is used and what is needed to initiate therapy and assess efficacy?

BACKGROUND: Superficial fungal infections are common. It is important to confirm the clinical diagnosis by mycological laboratory methods before initiating systemic antifungal treatment, especially as antifungal sensitivity and in vitro susceptibility may differ between different genera and species. For many years, the gold standard for diagnosis of superficial fungal infections has been direct fungal detection in the clinical specimen (microscopy) supplemented by culturing. Lately, newer molecular based methods for fungal identification have been developed. OBJECTIVE: This study was initiated to focus on the current usage of mycological diagnostics for superficial fungal infections by dermatologists. It was designed to investigate whether it was necessary to differentiate between initial diagnostic tests and those used at treatment follow-up in specific superficial fungal infections. METHODS: An online questionnaire was distributed among members of the EADV mycology Task Force and other dermatologists with a special interest in mycology and nail disease. RESULTS: The survey was distributed to 62 dermatologists of whom 38 (61%) completed the whole survey, 7 (11%) partially completed and 17 (27%) did not respond. Nearly, all respondents (82-100%) said that ideally they would use the result of direct microscopy (or histology) combined with a genus/species directed treatment of onychomycosis, dermatophytosis, Candida- and Malassezia-related infections. The majority of the dermatologists used a combination of clinical assessment and direct microscopy for treatment assessment and the viability of the fungus was considered more important at this visit than when initiating the treatment. Molecular based methods were not available for all responders. CONCLUSION: The available diagnostic methods are heterogeneous and their usage differs between different practices as well as between countries. The survey confirmed that dermatologists find it important to make a mycological diagnosis, particularly prior to starting oral antifungal treatment in order to confirm the diagnose and target the therapy according to genus and species

The self-assessed psychological comorbidities of prurigo in Europe: data from the ESDAP study

PS16 Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. The aim of this study was to assess the psychological burden of prurigo in patients of European countries. In this multicentre European study, 3, 635 general dermatology outpatients and 1, 359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected.There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10 of 27 (37%) suffered from anxiety and 8 of 27 (29%) from depression. Suicidal ideation was reported in 5 of 27 (19%) patients, and for 4 of these 5 patients, suicidal ideation was related to their skin disease. These frequencies were higher in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers). The impact on quality of life was severe, with a mean Dermatologic Life Quality Index (DLQI) of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients.The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments