Planar and Nonplanar Konishi Anomalies and Effective Superpotential for Noncommutative N=1 Supersymmetric U(1)

The Konishi anomalies for noncommutative N=1 supersymmetric U(1) gauge theory arising from planar and nonplanar diagrams are calculated. Whereas planar Konishi anomaly is the expected \star-deformation of the commutative anomaly, nonplanar anomaly reflects the important features of nonplanar diagrams of noncommutative gauge theories, such as UV/IR mixing and the appearance of nonlocal open Wilson lines. We use the planar and nonplanar Konishi anomalies to calculate the effective superpotential of the theory. In the limit of vanishing |\Theta p|, with \Theta the noncommutativity parameter, the noncommutative effective superpotential depends on a gauge invariant superfield, which includes supersymmetric Wilson lines, and has nontrivial dependence on the gauge field supermultiplet.Comment: LaTeX, 36 pages. Version 2: Typos Corrected. Version 3: Extensively revised version, 42 pages, to be published in Int. J. Mod. Phys. A. (2005

Structural Analysis of the Western Afar Margin, East Africa: Evidence for Multiphase Rotational Rifting

The Afar region in East Africa represents a key location to study continental breakup. We present an integrated structural analysis of the Western Afar Margin (WAM) aiming to better understand rifted margin development and the role of plate rotation during rifting. New structural information from remote sensing, fieldwork, and earthquake data sets reveals that the N-S striking WAM is still actively deforming and is characterized by NNW-SSE normal faulting as well as a series of marginal grabens. Seismicity distribution analysis and the first-ever borehole-calibrated sections of this developing passive margin show recent slip concentrated along antithetic faults. Tectonic stress parameters derived from earthquake focal mechanisms reveal different extension directions along the WAM (82°N), in Afar (66°N) and in the Main Ethiopian Rift (108°N). Fault slip analysis along the WAM yields the same extension direction. Combined with GPS data, this shows that current tectonics in Afar is dominated by the local rotation of the Danakil Block, considered to have occurred since 11 Ma. Earlier stages of Afar development (since 31–25 Ma) were most likely related to the large-scale rotation of the Arabian plate. Various authors have proposed scenarios for the evolution of the WAM. Any complete model should consider, among other factors, the multiphase tectonic history and antithetic fault activity of the margin. The findings of this study are not only relevant for a better understanding of the WAM but also provide insights into the role of multiphase rotational extension during rifting and passive margin formation in general.</p

Health Visiting and School Nursing Programmes: supporting implementation of the new service model No.5: Domestic Violence and Abuse – Professional Guidance

Guidance created by an expert working group at the Department of Healt

Work-time underemployment and financial hardship: class inequalities and recession in the UK

The economic crisis that led to recession in the UK in 2008–9 impacted in multiple ways on work and economic life. This article examines changes to the work-time of employees. The UK stood out for its recessionary expansion of work-time underemployment. Working in a job that provides ‘too few’ hours can have serious ramifications for the economic livelihood of workers. Working-class workers are central here. Drawing on analysis of large-scale survey data, the article identifies that workers in lower level occupations experienced the most substantial post-recessionary growth in the proportions working ‘too few’ hours. Did these work-time changes narrow or widen class inequalities in feelings of financial hardship? The article concludes that although middle-class workers also saw their financial positions damaged, this so-called ‘first middle-class recession’ did not erode class inequalities in financial hardship among UK workers

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001). Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term

Single-cell analysis implicates Th17-to-Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis

Background Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder, characterised by eruptions of painful, neutrophil-filled pustules on the palms and soles. While PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat. Objective We sought to investigate the immune pathways that underlie the pathogenesis of PPP. Methods We applied bulk- and single-cell RNA-sequencing methods to the analysis of skin biopsies and peripheral blood mononuclear cells. We validated our results by flow cytometry and immune fluorescence microscopy Results Bulk RNA-sequencing of patient skin detected an unexpected signature of T-cell activation, with a significant overexpression of several Th2 genes typically upregulated in atopic dermatitis. To further explore these findings, we carried out single-cell RNA-sequencing in peripheral blood mononuclear cells of healthy and affected individuals. We found that the memory CD4+T-cells of PPP patients were skewed towards a Th17 phenotype, a phenomenon that was particularly significant among CLA+ skin-homing cells. We also identified a subset of memory CD4+ T-cells which expressed both Th17 (KLRB1/CD161) and Th2 (GATA3) markers, with pseudo-time analysis suggesting that the population was the result of Th17 to Th2 plasticity. Interestingly, the GATA3+/CD161+ cells were over-represented among the PBMCs of affected individuals, both in the scRNA-seq dataset and in independent flow-cytometry experiments. Dual positive cells were also detected in patient skin by means of immune fluorescence microscopy. Conclusions These observations demonstrate that PPP is associated with complex T-cell activation patterns and may explain why biologics that target individual T-helper populations have shown limited therapeutic efficacy. Clinical implications The simultaneous activation of Th17 and Th2 responses in PPP supports the therapeutic use of agents that inhibit multiple T-cell pathways

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de)

Randomised controlled trial of topical corticosteroid and home?based narrowband UVB for active and limited vitiligo: results of the HI?Light Vitiligo trial

BackgroundEvidence for the effectiveness of vitiligo treatments is limited.ObjectivesTo determine effectiveness of (a) hand‐held narrowband‐UVB (NB‐UVB) and (b) combination of potent topical corticosteroid (TCS) and NB‐UVB compared to TCS, for localised vitiligo.MethodsPragmatic, 3‐arm, placebo‐controlled RCT (9 months’ treatment; 12 months’ follow‐up). Adults and children, recruited from secondary care and community, aged ≥5 years with active vitiligo affecting 75% expected were more likely to achieve treatment success, but effects were lost once treatment stopped. Localised grade 3 or 4 erythema was reported in 62 (12%) participants (including 3 with dummy light). Skin thinning was reported in 13 (2.5%) participants (including 1 with placebo ointment).ConclusionCombination treatment with home‐based hand‐held NB‐UVB plus TCS is likely to be superior to TCS alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated but was only successful in around a quarter of participants