Electrostatics in a simple wormhole revisited

The electrostatic potential generated by a point charge at rest in a simple static, spherically symmetric wormhole is given in the form of series of multipoles and in closed form. The general potential which is physically acceptable depends on a parameter due to the fact that the monopole solution is arbitrary. When the wormhole has Z2-symmetry, the potential is completely determined. The calculation of the electrostatic self-energy and of the self-force is performed in all cases considered.Comment: 16 pages, no figure

From Rotating Atomic Rings to Quantum Hall States

Considerable efforts are currently devoted to the preparation of ultracold neutral atoms in the emblematic strongly correlated quantum Hall regime. The routes followed so far essentially rely on thermodynamics, i.e. imposing the proper Hamiltonian and cooling the system towards its ground state. In rapidly rotating 2D harmonic traps the role of the transverse magnetic field is played by the angular velocity. For particle numbers significantly larger than unity, the required angular momentum is very large and it can be obtained only for spinning frequencies extremely near to the deconfinement limit; consequently, the required control on experimental parameters turns out to be far too stringent. Here we propose to follow instead a dynamic path starting from the gas confined in a rotating ring. The large moment of inertia of the fluid facilitates the access to states with a large angular momentum, corresponding to a giant vortex. The initial ring-shaped trapping potential is then adiabatically transformed into a harmonic confinement, which brings the interacting atomic gas in the desired quantum Hall regime. We provide clear numerical evidence that for a relatively broad range of initial angular frequencies, the giant vortex state is adiabatically connected to the bosonic $\nu=1/2$ Laughlin state, and we discuss the scaling to many particles.Comment: 9 pages, 5 figure

Woven natural fibre reinforced composite materials for medical imaging

Repeatable patient positioning is key to minimising the burden on planning radiotherapy treatment. There are very few materials commercially available which are suitable for use in all common imaging and treatment modalities such as magnetic resonance imaging (MRI), X-Ray computed tomography (CT) and radiotherapy. In this article, we present several such materials based on woven natural fibres embedded in a range of different resin materials which are suitable for such applications. By investigating a range of resins and natural fibre materials in combination and evaluating their performance in terms of MRI and X-Ray imaging, we show that a woven cotton material impregnated with a two-part epoxy resin provides a 15% improvement in passage of X-Rays and has no impact on the MRI signal (unlike the 40% MRI signal attenuation from carbon fibre), whilst also retaining a flexural modulus up to 71% of that of carbon fibre. These results demonstrate that natural fibre composites produced using such materials provide desirable properties for use in patient support and positioning devices for multi-modal imaging, without the need to significantly compromise on the strength of the material

Evaluating Performance of Web Applications in (Cloud) Virtualized Environments

Web applications usually involve a number of different software libraries and tools (usually referred to as frameworks) each carrying out specific task/s and generating the corresponding overhead. In this paper, we show how to evaluate and even find out several configuration performance characteristics by using virtualized environments which are now used in data centers and cloud environments. We use specific and simple web software architectures as proof of concept, and explain several experiments that show performance issues not always expected from a conceptual point of view. We also explain that adding software libraries and tools also generate performance analysis complexities. We also shown that as an application is shown to scale, the problems to identify performance details and bottlenecks also scale, and the performance analysis also requires deeper levels of details.Instituto de Investigación en Informátic

Advanced sandwich composite cores for patient support in advanced clinical imaging and oncology treatment

Ongoing advances in both imaging and treatment for oncology purposes have seen a significant rise in the use of not only the individual imaging modalities, but also their combination in single systems such as Positron Emission Tomography combined with Computed Tomography (PET–CT) and PET–MRI (Magnetic Resonance Imaging) when planning for advanced oncology treatment, the most demanding of which is proton therapy. This has identified issues in the availability of suitable materials upon which to support the patient undergoing imaging and treatment owing to the differing requirements for each of the techniques. Sandwich composites are often selected to solve this issue but there is little information regarding optimum materials for their cores. In this paper, we presented a range of materials which are suitable for such purposes and evaluated the performance for use in terms of PET signal attenuation, proton beam stopping, MRI signal shading and X-Ray CT visibility. We found that Extruded Polystyrene offers the best compromise for patient support and positioning structures across all modalities tested, allowing for significant savings in treatment planning time and delivering more efficient treatment with lower margins

Infrared imaging and spectroscopy of the Luminous Blue Variables Wra 751 and AG Car

We present ground-based infrared imaging and ISO spectroscopy of the luminous blue variables Wra 751 and AG Car. The images show in both cases a detached shell with a roughly circular distribution of emission. The infrared images of AG Car coincide very well with the optical images. The optical (H[FORMULA]) image of Wra 751 is different from the infrared image; the H[FORMULA] nebula is suggested to be a scattering nebula containing cold dust particles. Fitting both the images and the spectra consistently with a 1-D radiative transfer model, we derive properties of their dust shells. Wra 751 is surrounded by a dust shell with inner and outer radii of 0.17 and 0.34 pc respectively and a dust mass of 0.017 [FORMULA]. The dust shell of AG Car has inner and outer radii of 0.37 and 0.81 pc respectively and a total dust mass of 0.25 [FORMULA]. Dust mass-loss rates during the formation of the shells are 2.7[FORMULA] and 3.4[FORMULA] [FORMULA] yr-1, respectively. The total dust mass and hence the derived dust mass-loss rates are uncertain by at least a factor of two. For AG Car, the derived dust mass and mass-loss rate are higher than previous estimates. This is mainly caused by the fact that a contribution of very large grains ([FORMULA] 10 µm) is needed to explain the flux levels at longer wavelengths. Dust models for both objects fail to explain the flux shortward of 15 to 20 µm: a population of small warm grains, not in thermal equilibrium with the central star is necessary to explain this excess. Similarities between dust shells around Wolf-Rayet stars and Wra 751 and AG Car (mass, grain size population, morphology) suggest a similar formation history and imply an evolutionary connection. A similar connection with red supergiants is suggested on the basis of the dust composition and derived time-averaged mass-loss rates

Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP

Linear ubiquitin chains are important regulators of cellular signaling pathways that control innate immunity and inflammation through NF-κB activation and protection against TNFα-induced apoptosis(1-5). They are synthesized by HOIP, which belongs to the RBR (RING-between-RING) family of E3 ligases and is the catalytic component of LUBAC (linear ubiquitin chain assembly complex), a multi-subunit E3 ligase(6). RBR family members act as RING/HECT hybrids, employing RING1 to recognize ubiquitin-loaded E2 while a conserved cysteine in RING2 subsequently forms a thioester intermediate with the transferred or “donor” ubiquitin(7). Here we report the crystal structure of the catalytic core of HOIP in its apo form and in complex with ubiquitin. The C-terminal portion of HOIP adopts a novel fold that, together with a zinc finger, forms an ubiquitin-binding platform which orients the acceptor ubiquitin and positions its α-amino group for nucleophilic attack on the E3~ubiquitin thioester. The carboxy-terminal tail of a second ubiquitin molecule is located in close proximity to the catalytic cysteine providing a unique snapshot of the ubiquitin transfer complex containing both donor and acceptor ubiquitin. These interactions are required for activation of the NF-kB pathway in vivo and explain the determinants of linear ubiquitin chain specificity by LUBAC

An international randomised controlled trial to compare targeted intra-operative radiotherapy (TARGIT) with conventional post-operative radiotherapy after conservative breast surgery for women with early stage breast cancer (The TARGIT-A trial)

BACKGROUND: Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed - the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies. OBJECTIVE: To compare TARGIT within a risk-adapted approach with whole breast external beam radiotherapy over several weeks (EBRT). DESIGN AND SETTING: The TARGIT-A trial was a pragmatic, prospective, international, multicenter, non-inferiority, non-blinded, randomised (1:1 ratio), clinical trial from 33 centres in 11 countries. Originally, randomisation occurred before initial lumpectomy (prepathology) and if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added, in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but needed a reoperation to reopen the wound to give TARGIT as delayed procedure. Risk-adapted approach meant that in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, then EBRT was recommended. Pragmatically, this reflected how TARGIT would be practiced in the real world. PARTICIPANTS: Women who were >=45 years of age with unifocal invasive ductal carcinoma preferably <= 3.5cm in size; 3451 patients were recruited between March 2000 and June 2012. OUTCOMES: Primary: absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary: included toxicity, breast cancer specific and non-breast-cancer mortality. RESULTS: Values below are 5-year Kaplan-Meier rates for TARGIT vs. EBRT. There was no statistically significant difference in local recurrence between TARGIT and EBRT. TARGIT was non-inferior to EBRT overall (3·3%(2·1–5·1) vs. 1·3%(0·7–2·5),p=0.04,Pnoninferiority =0.00000012) and in the prepathology stratum(n=2298) when TARGIT was given concurrently with lumpectomy(2·1%(1·1–4·2) vs. 1·1%(0·5–2·5),p=0.31,Pnoninferiority =0.0000000013). With delayed TARGIT postpathology,(n=1153) the between-group difference was larger than 2·5% and non-inferiority was not established for this stratum((5·4%(3·0–9·7) vs. 1·7%(0·6–4·9),p=0.069,Pnoninferiority= 0.06640). The local-recurrence-free survival when TARGIT was given with lumpectomy was 93.9%(95%CI 90.9 – 95.9) vs. EBRT: 92.5%(95%CI 89.7 – 94.6),p=0.35. In a planned subgroup analysis, progesterone (PgR) receptor status was found to be the only predictor of outcome - hormone responsive patients (PgRpositive) had similar 5-year local recurrence with TARGIT during lumpectomy 1.4%(0.5-3.9) vs. EBRT 1.2%(0.5-2.9),p=0.77. Grade 3 or 4 radiotherapy toxicity was significantly reduced with TARGIT. Overall, breast cancer mortality was much the same between groups (2·6%[1·5–4·3] vs. 1·9%[1·1–3·2];p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8–2·5] vs 3·5%[2·3–5·2];p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers, leading to a trend in reduced overall mortality in the TARGIT arm 37 deaths, 3·9%(2·7–5·8) vs. 51 deaths, 5·3%(3·9–7·3),p=0.099). Health economic analyses suggest that TARGIT was statistically significantly less costly than EBRT, produced similar QALYs, had a positive incremental Net Monetary Benefit that was borderline statistically significant from zero, and had a probability of over 90% of being cost-effective. There appears to be little uncertainty in the point estimates, based on deterministic and probabilistic sensitivity analyses. If TARGIT were given instead of EBRT in suitable patients, it might potentially reduce costs to the health care providers by £8 million to £9.1 million each year. This does not include environmental, patient and societal costs. LIMITATIONS: The number of local recurrences is small however, the number of events for local-recurrence-free survival is not small (59 vs. 61); Occurrence of only a few events implies that the treatments are effective and any difference is unlikely to be large. The follow up not all 3451 patients is 5 years, although the number required to answer the main trial question (n=585) have more than 5 years follow up. FUTURE WORK: We shall repeat the analyses with longer follow up. Although this may not change the primary result, the larger number of events may confirm the effect on mortality and allow more detailed subgroup analyses. The TARGIT-B trial is testing whether TARGIT-Boost is superior to EBRT boost. CONCLUSION: For patients with breast cancer (women who are 45 years of age and older with hormone sensitive invasive ductal carcinoma that is up to 3.5cm in size), TARGIT concurrent with lumpectomy within a risk-adapted approach is as effective, safer and less expensive alternative to postoperative EBRT. TRIAL REGISTRATION: ISRCTN34086741, ClinicalTrials.gov NCT00983684

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine

Pulmonary Metastasectomy in Colorectal Cancer burden of care study: analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort

AIM: To examine the burden of further treatments in patients with colorectal cancer (CRC) following a decision about lung metastasectomy. METHODS: Five teams participating in the study of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) provided details on subsequent local treatments for lung metastases including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined. RESULTS: The five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 had one, and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with non-elevated CEA, fewer metastases, and no prior liver metastasectomy. These patients also had better ECOG scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had 1-5 courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee-time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed with no apparent reduction in chemotherapy usage. CONCLUSION: Repeated metastasectomy is associated with higher risk of death without reducing use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy