Magma flow through elastic-walled dikes

A convection–diffusion model for the averaged flow of a viscous, incompressible magma through an elastic medium is considered. The magma flows through a dike from a magma reservoir to the Earth’s surface; only changes in dike width and velocity over large vertical length scales relative to the characteristic dike width are considered. The model emerges when nonlinear inertia terms in the momentum equation are neglected in a viscous, low-speed approximation of a magma flow model coupled to the elastic response of the rock.\ud Stationary- and traveling-wave solutions are presented in which a Dirichlet condition is used at the magma chamber; and either a (i) free-boundary condition, (ii) Dirichlet condition, or (iii) choked-flow condition is used at the moving free or fixed-top boundary. A choked-flow boundary condition, generally used in the coupled elastic wave and magma flow model, is also used in the convection–diffusion model. The validity of this choked-flow condition is illustrated by comparing stationary flow solutions of the convection–diffusion and coupled elastic wave and magma flow model for parameter values estimated for the Tolbachik volcano region in Kamchatka, Russia. These free- and fixed-boundary solutions are subsequently explored in a conservative, local discontinuous Galerkin finite-element discretization. This method is advantageous for the accurate implementation of the choked flow and free-boundary conditions. It uses a mixed Eulerian–Lagrangian finite element with special infinite curvature basis function near the free boundary and ensures positivity of the mean aperture subject to a time-step restriction. We illustrate the model further by simulating magma flow through host rock of variable density, and magma flow that is quasi-periodic due to the growth and collapse of a lava dome

Number of Patients Studied Prior to Approval of New Medicines: A Database Analysis

Background: At the time of approval of a new medicine, there are few long-term data on the medicine's benefit-risk balance. Clinical trials are designed to demonstrate efficacy, but have major limitations with regard to safety in terms of patient exposure and length of follow-up. This study of the number of patients who had been administered medicines at the time of medicine approval by the European Medicines Agency aimed to determine the total number of patients studied, as well as the number of patients studied long term for chronic medication use, compared with the International Conference on Harmonisation's E1 guideline recommendations. Methods and Findings: All medicines containing new molecular entities approved between 2000 and 2010 were included in the study, including orphan medicines as a separate category. The total number of patients studied before approval was extracted (main outcome). In addition, the number of patients with long-term use (6 or 12 mo) was determined for chronic medication. 200 unique new medicines were identified: 161 standard and 39 orphan medicines. The median total number of patients studied before approval was 1,708 (interquartile range [IQR] 968-3,195) for standard medicines and 438 (IQR 132-915) for orphan medicines. On average, chronic medication was studied in a larger number of patients (median 2,338, IQR 1,462-4,135) than medication for intermediate (878, IQR 513-1,559) or short-term use (1,315, IQR 609-2,420). Safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least 6 and 12 mo in 46.4% and 58.3% of new medicines, respectively. Among t

Source population synthesis and the Galactic diffuse gamma-ray emission

Population synthesis is used to study the contribution from undetected sources to the Galactic ridge emission measured by EGRET. Synthesized source counts are compared with the 3rd EGRET catalogue at low and high latitudes. For pulsar-like populations, 5-10% of the emission >100 MeV comes from sources below the EGRET threshold. A steeper luminosity function can increase this to 20% without violating EGRET source statistics. Less luminous populations can produce much higher values without being detected. Since the unresolved source spectrum is different from the interstellar spectrum, it could provide an explanation of the observed MeV and GeV excesses above the predictions, and we give an explicit example of how this could work.Comment: Astrophysics and Space Science, in press. (Proceedings of Conference 'The multi-messenger approach to high-energy gamma-ray sources', Barcelona, 2006). Minor changes for accepted version, updated reference

Molecular characterization and phylogeny of Shiga toxin–producing Escherichia coli isolates obtained from two Dutch regions using whole genome sequencing

AbstractShiga toxin–producing Escherichia coli (STEC) is one of the major causes of human gastrointestinal disease and has been implicated in sporadic cases and outbreaks of diarrhoea, haemorrhagic colitis and haemolytic uremic syndrome worldwide. In this study, we determined the molecular characteristics and phylogenetic relationship of STEC isolates, and their genetic diversity was compared to that of other E. coli populations. Whole genome sequencing was performed on 132 clinical STEC isolates obtained from the faeces of 129 Dutch patients with gastrointestinal complaints. STEC isolates of this study belonged to 44 different sequence types (STs), 42 serogenotypes and 14 stx subtype combinations. Antibiotic resistance genes were more frequently present in stx1-positive isolates compared to stx2 and stx1 + stx2–positive isolates. The iha, mchB, mchC, mchF, subA, ireA, senB, saa and sigA genes were significantly more frequently present in eae-negative than in eae-positive STEC isolates. Presence of virulence genes encoding type III secretion proteins and adhesins was associated with isolates obtained from patients with bloody diarrhoea. Core genome phylogenetic analysis showed that isolates clustered according to their ST or serogenotypes irrespective of stx subtypes. Isolates obtained from patients with bloody diarrhoea were from diverse phylogenetic backgrounds. Some STEC isolates shared common ancestors with non-STEC isolates. Whole genome sequencing is a powerful tool for clinical microbiology, allowing high-resolution molecular typing, population structure analysis and detailed molecular characterization of strains. STEC isolates of a substantial genetic diversity and of distinct phylogenetic groups were observed in this study

Screening and time trend study of decabromodiphenylether in birds

In 2001, Swedish scientists reported the presence of decabromodiphenylether (DBDE) in peregrine falcons. Subsequently, we have carried out an extensive study on the presence and time trends of DBDE in predatory birds and water birds in order to provide information on this subject for the European environmental risk assessment of DBDE. The UK Environment Agency and the Bromine Science and Environmental Forum (BSEF) initiated the study

Українська сангха японського Ордену Ніппондзан Мьоходзі

Стаття присвячена дослідженню історії української сангхи японського буддистського Ордену Ніппондзан Мьоходзі. Автор, враховуючи специфіку даної школи, намагався намітити загальний шлях для подальшого дослідження, виявити основні тенденції та періоди розвитку української сангхи Ніппондзан Мьоходзі. Значна увага приділяється діяльності членів української сангхи за межами України, що обумовлено світовими масштабами діяльності Дзюнсея Терасави, безпосереднього вчителя для українських монахів даного ОрденуСтатья посвящена исследованию истории украинской сангхи японского буддийского Ордена Ниппондзан Мёходзи. Автор, учитывая специфику данной школы, старался наметить общий путь для дальнейшего исследования, выявить основные тенденции и периоды развития украинской сангхи Ниппондзан Мёходзи. Значительное внимание уделяется деятельности членов украинской сангхи за пределами Украины, что обусловлено мировыми масштабами деятельности Дзюнсея Терасавы, непосредственного учителя монахов данного Ордена.This article is devoted to the history of Ukrainian Sangha of Japanese Buddhist Order Nippondzan Mehodzi. Taking into account the specificity of the school, the author trying to direct a common way for further research, to identify the key trends and periods of development of Ukrainian Sangha Nippondzan Mehodozi. Considerable attention has been given to the activities of the Ukrainian Sangha members outside of Ukraine, wich is caused by the global scale of Dzyunsey Terasava activity

SAAP-148 eradicates MRSA persisters within mature biofilm models simulating prosthetic joint infection

Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.Orthopaedics, Trauma Surgery and Rehabilitatio

The impact of bone marrow sparing on organs at risk dose for cervical cancer: a Pareto front analysis

Background and purpose: To quantify the increase in bladder and rectum dose of a bone marrow sparing (BMS) VMAT strategy for primary treatment of locally advanced cervical cancer (LACC).Materials and methods: Twenty patients with stage IB-IVA cervical cancer were selected for this study. The whole Pelvic Bones (PB) was taken as substitute for bone marrow. For every patient, Pareto-optimal plans were generated to explore the trade-off between rectum, bladder, and PB mean dose. The PB mean dose was decreased in steps of 1 Gy. For each step, the increase in rectum and bladder mean dose was quantified. The increase in mean dose of other OAR compared to no BMS was constrained to 1 Gy.Results: In total, 931 plans of 19 evaluable patients were analyzed. The average [range] mean dose of PB without BMS was 22.8 [20.7-26.2] Gy. When maximum BMS was applied, the average reduction in mean PB dose was 5.4 [3.0-6.8] Gy resulting in an average mean PB dose of 17.5 [15.8-19.8] Gy. For 2 Gy, >3 Gy, >4 Gy, and >5 Gy for 19/19, 13/19, 5/19, and 1/19 patients, respectively.Conclusion: Based on the comprehensive three-dimensional Pareto front analysis, we conclude that 2-5 Gy BMS can be implemented without a clinically relevant increase in mean dose to other OAR. If BMS is too dominant, it results in a large increase in mean dose to other OAR. Therefore, we recommend implementing moderate BMS for the treatment of LACC patients with VMAT.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Residual Type 1 Immunity in Patients Genetically Deficient for Interleukin 12 Receptor β1 (IL-12Rβ1): Evidence for an IL-12Rβ1–Independent Pathway of IL-12 Responsiveness in Human T Cells

Genetic lack of interleukin 12 receptor β1 (IL-12Rβ1) surface expression predisposes to severe infections by poorly pathogenic mycobacteria or Salmonella and causes strongly decreased, but not completely abrogated, interferon (IFN)-γ production. To study IL-12Rβ1–independent residual IFN-γ production, we have generated mycobacterium–specific T cell clones (TCCs) from IL-12Rβ1–deficient individuals. All TCCs displayed a T helper type 1 phenotype and the majority responded to IL-12 by increased IFN-γ production and proliferative responses upon activation. This response to IL-12 could be further augmented by exogenous IL-18. IL-12Rβ2 was found to be normally expressed in the absence of IL-12Rβ1, and could be upregulated by IFN-α. Expression of IL-12Rβ2 alone, however, was insufficient to induce signal transducer and activator of transcription (Stat)4 activation in response to IL-12, whereas IFN-α/IFN-αR ligation resulted in Stat4 activation in both control and IL-12Rβ1–deficient cells. IL-12 failed to upregulate cell surface expression of IL-18R, integrin α6, and IL-12Rβ2 on IL-12Rβ1–deficient cells, whereas this was normal on control cells. IL-12–induced IFN-γ production in IL-12Rβ1–deficient T cells could be inhibited by the p38 mitogen-activated protein kinase (MAP) kinase inhibitor SB203580 and the MAP kinase kinase (MEK) 1/2 inhibitor U0126, suggesting involvement of MAP kinases in this alternative, Stat4-independent, IL-12 signaling pathway