Multi-dimensional tunnelling and complex momentum

The problem of modeling tunneling phenomena in more than one dimension is examined. It is found that existing techniques are inadequate in a wide class of situations, due to their inability to deal with concurrent classical motion. The generalization of these methods to allow for complex momenta is shown, and improved techniques are demonstrated with a selection of illustrative examples. Possible applications are presented

Tunnelling from non-localised initial states

An approach for calculating tunneling amplitudes from a nonlocalized initial state is presented. Generalizing the matching conditions and equations of motion to allow for complex momentum permits a description of tunneling in the presence of so-called classical motion. Possible applications of the method are presented

Expression and Functional Studies on the Noncoding RNA, PRINS.

PRINS, a noncoding RNA identified earlier by our research group, contributes to psoriasis susceptibility and cellular stress response. We have now studied the cellular and histological distribution of PRINS by using in situ hybridization and demonstrated variable expressions in different human tissues and a consistent staining pattern in epidermal keratinocytes and in vitro cultured keratinocytes. To identify the cellular function(s) of PRINS, we searched for a direct interacting partner(s) of this stress-induced molecule. In HaCaT and NHEK cell lysates, the protein proved to be nucleophosmin (NPM) protein as a potential physical interactor with PRINS. Immunohistochemical experiments revealed an elevated expression of NPM in the dividing cells of the basal layers of psoriatic involved skin samples as compared with healthy and psoriatic uninvolved samples. Others have previously shown that NPM is a ubiquitously expressed nucleolar phosphoprotein which shuttles to the nucleoplasm after UV-B irradiation in fibroblasts and cancer cells. We detected a similar translocation of NPM in UV-B-irradiated cultured keratinocytes. The gene-specific silencing of PRINS resulted in the retention of NPM in the nucleolus of UV-B-irradiated keratinocytes; suggesting that PRINS may play a role in the NPM-mediated cellular stress response in the skin

Selftuning and its footprints

We re-consider the self tuning idea in brane world models of finite volume. We notice that in a large class of self tuning models, the four dimensional physics is sensitive to the vacuum energy on the brane. In particular the compactification volume changes each time the tension of the brane is modified: consequently, observable constants, as the effective Planck mass or masses of matter fields, change as well. We notice that the self tuning mechanism and the stabilization mechanism of the size of the extra dimensions are generically in apparent conflict. We focus on a self tuning model in six spacetime dimensions to analyze how the above considerations are explicitely realized.Comment: 28 pages, JHEP style. v2: typos corrected and references added. Published versio

Bouncing and cyclic universes from brane models

We consider a D3-brane as boundary of a five dimensional charged anti de Sitter black hole. We show that the charge of the black hole induces a regular cosmological evolution for the scale factor of the brane, with a smooth transition between a contracting and an eventual expanding phase. Simple analytical solutions can be obtained in the case of a vanishing effective cosmological constant on the brane. A nonvanishing cosmological constant, or the inclusion of radiation on the brane, does not spoil the regularity of these solutions at small radii, and observational constraints such as the ones from primordial nucleosynthesis can be easily met. Fluctuations of brane fields remain in the linear regime provided the minimal size of the scale factor is sufficiently large. We conclude with an analysis of the Cardy-Verlinde formula in this set up.Comment: 13 pages, final versio

Presenting Symptoms in Newly Diagnosed Myeloma, Relation to Organ Damage, and Implications for Symptom-Directed Screening: A Secondary Analysis from the Tackling Early Morbidity and Mortality in Myeloma (TEAMM) Trial

Multiple myeloma (MM) patients risk diagnostic delays and irreversible organ damage. In those with newly diagnosed myeloma, we explored the presenting symptoms to identify early signals of MM and their relationships to organ damage. The symptoms were recorded in patients’ own words at diagnosis and included diagnostic time intervals. Those seen by a haematologist >6 months prior to MM diagnosis were classified as precursor disease (PD). Most (962/977) patients provided data. Back pain (38%), other pain (31%) and systemic symptoms (28%) predominated. Patients rarely complain of ‘bone pain’, simply ‘pain’. Vertebral fractures are under-recognised as pathological and are the predominant irreversible organ damage (27% of patients), impacting the performance status (PS) and associated with back pain (odds ratio (OR) 6.14 [CI 4.47–8.44]), bone disease (OR 3.71 [CI 1.88–7.32]) and age >65 years (OR 1.58 [CI 1.15–2.17]). Renal failure is less frequent and associated with gastrointestinal symptoms (OR 2.23 [CI1.28–3.91]), age >65 years (OR 2.14 [CI1.28–3.91]) and absence of back pain (OR 0.44 [CI 0.29–0.67]). Patients with known PD (n = 149) had fewer vertebral fractures (p = 0.001), fewer adverse features (p = 0.001), less decline in PS (p = 0.001) and a lower stage (p = 0.04) than 813 with de novo MM. Our data suggest subgroups suitable for trials of ‘symptom-directed’ screening: those with back pain, unexplained pain, a general decline in health or low-impact vertebral compression fractures

Higher spin AdS_3 supergravity and its dual CFT

Vasiliev's higher spin supergravity theory on three dimensional anti-de Sitter space is studied and, in particular, the partition function is computed at one loop level. The dual conformal field theory is proposed to be the N=(2,2) CP^N Kazama-Suzuki model in two dimensions. The proposal is based on symmetry considerations and comparison of the bulk partition function with the conformal field theory. Our findings suggest that the theory is strong-weak self-dual.Comment: 36 page

Higher spin AdS_3 holography with extended supersymmetry

We propose a holographic duality between a higher spin AdS_3 gravity with so(p) extended supersymmetry and a large N limit of a 2-dimensional Grassmannian-like model with a specific critical level k=N and a non-diagonal modular invariant. As evidence, we show the match of one-loop partition functions. Moreover, we construct symmetry generators of the coset model for low spins which are dual to gauge fields in the supergravity. Further, we discuss a possible relation to superstring theory by noticing an N=3 supersymmetry of critical level model at finite k,N. In particular, we examine BPS states and marginal deformations. Inspired by the supergravity side, we also propose and test another large N CFT dual obtained as a Z_2 automorphism truncation of a similar coset model, but at a non-critical level.Comment: 44 pages, published versio

Cosmological Perturbations in a Big Crunch/Big Bang Space-time

A prescription is developed for matching general relativistic perturbations across singularities of the type encountered in the ekpyrotic and cyclic scenarios i.e. a collision between orbifold planes. We show that there exists a gauge in which the evolution of perturbations is locally identical to that in a model space-time (compactified Milne mod Z_2) where the matching of modes across the singularity can be treated using a prescription previously introduced by two of us. Using this approach, we show that long wavelength, scale-invariant, growing-mode perturbations in the incoming state pass through the collision and become scale-invariant growing-mode perturbations in the expanding hot big bang phase.Comment: 47 pages, 4 figure

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research