Systematic review: Histological remission in inflammatory bowel disease. Is ‘complete’ remission the new treatment paradigm? An IOIBD initiative

AbstractBackground and aimsAdvances in the medical management of inflammatory bowel disease (IBD) have altered treatment targets. Endoscopic mucosal healing is associated with better outcomes in IBD, though less is known about the significance of achieving histological remission. Our aim was to perform a systematic review to investigate whether histological or ‘complete’ remission constitutes a further therapeutic target in IBD.MethodsA bibliographic search was performed on the 1st of October 2013 and subsequently on the 1st of March 2014 of online databases (OVID SP MEDLINE, OVID EMBASE, National Pubmed Central Medline, Cochrane Library, ISI, conference abstracts), using MeSH terms and key words: (“inflammatory bowel diseases” OR “crohn disease” OR “ulcerative colitis” OR “colitis”) AND (“mucosal healing” OR “histological healing” OR “pathological healing” OR “histological scoring” OR “pathological scoring”).ResultsThe search returned 2951 articles. 120 articles were cited in the final analysis. There is no validated definition of histological remission in IBD. There are 22 different histological scoring systems for IBD, none of which are fully validated. Microscopic inflammation persists in 16–100% of cases of endoscopically quiescent disease. There is evidence that histological remission may predict risk of complications in ulcerative colitis beyond endoscopic mucosal healing, though data are scarce in Crohn's disease.ConclusionsHistological remission in IBD represents a target distinct from endoscopic mucosal healing, not yet routinely sought in clinical trials or practice. There remains a need for a standardized and validated histological scoring system and to confirm the prognostic value of histological remission as a treatment target in IBD

On manifolds with nonhomogeneous factors

We present simple examples of finite-dimensional connected homogeneous spaces (they are actually topological manifolds) with nonhomogeneous and nonrigid factors. In particular, we give an elementary solution of an old problem in general topology concerning homogeneous spaces

Renormalization approach for quantum-dot structures under strong alternating fields

We develop a renormalization method for calculating the electronic structure of single and double quantum dots under intense ac fields. The nanostructures are emulated by lattice models with a clear continuum limit of the effective-mass and single-particle approximations. The coupling to the ac field is treated non-perturbatively by means of the Floquet Hamiltonian. The renormalization approach allows the study of dressed states of the nanoscopic system with realistic geometries as well arbitrary strong ac fields. We give examples of a single quantum dot, emphasizing the analysis of the effective-mass limit for lattice models, and double-dot structures, where we discuss the limit of the well used two-level approximation.Comment: 6 pages, 7 figure

Spin interactions and switching in vertically tunnel-coupled quantum dots

We determine the spin exchange coupling J between two electrons located in two vertically tunnel-coupled quantum dots, and its variation when magnetic (B) and electric (E) fields (both in-plane and perpendicular) are applied. We predict a strong decrease of J as the in-plane B field is increased, mainly due to orbital compression. Combined with the Zeeman splitting, this leads to a singlet-triplet crossing, which can be observed as a pronounced jump in the magnetization at in-plane fields of a few Tesla, and perpendicular fields of the order of 10 Tesla for typical self-assembled dots. We use harmonic potentials to model the confining of electrons, and calculate the exchange J using the Heitler-London and Hund-Mulliken technique, including the long-range Coulomb interaction. With our results we provide experimental criteria for the distinction of singlet and triplet states and therefore for microscopic spin measurements. In the case where dots of different sizes are coupled, we present a simple method to switch on and off the spin coupling with exponential sensitivity using an in-plane electric field. Switching the spin coupling is essential for quantum computation using electronic spins as qubits.Comment: 13 pages, 9 figure

Bullying behaviors and victimization experiences among adolescent students: the role of resilience

The role of resilience in the relationship between bullying behaviours, victimisation experiences, and self-efficacy was examined. Three hundred and 93 (191 male, 202 female) adolescents (mean age = 15.88, SD = .64) from schools in Coimbatore, India completed scales to assess bullying behaviours and victimisation experiences, resilience, and self-efficacy. Multigroup SEM, with separate groups created according to participant sex, revealed that resilience mediated the relationship between bullying behaviours and self-efficacy in males. Males engaged in bullying behaviours and experienced victimisation more frequently than females. The findings of the study have implication for designing intervention programs to enhance resilience among adolescents and young adults to enable them to manage bullying behaviours

Search for double-β decay of 130Te to the first 0+ excited state of 130Xe with the CUORICINO experiment bolometer array

The CUORICINO experiment was an array of 62 TeO2 single-crystal bolometers with a total 130Te mass of 11.3kg. The experiment finished in 2008 after more than 3 yr of active operating time. Searches for both 0ν and 2ν double-β decay to the first excited 0+ state in 130Xe were performed by studying different coincidence scenarios. The analysis was based on data representing a total exposure of N(130Te)⋅t=9.5×1025yr. No evidence for a signal was found. The resulting lower limits on the half-lives are T2ν12(130Te→130Xe∗)\u3e1.3×1023yr (90% C.L.), and T0ν12(130Te→130Xe∗)\u3e9.4×1023yr (90% CL)

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

CUORE Experiment: The Search for Neutrrinoless Double Beta Decay

The main purpose of the Cryogenic Underground Observatory for Rare Events (CUORE) experiment is the search for the Neutrinoless Double Beta Decay (0νDBD) of n130Te reaching a sensitivity on Majorana mass better than 50 meV. Cuoricino represents not only the first stage of CUORE, but also the most massive 0νDBD experiment presently running. Present results and future planning of these experiments will be described in the paper