Pharmacokinetic profiles of the active metamizole metabolites in healthy horses

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among other secondary metabolites, 4-aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 9 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC-UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0-last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0-last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug

Materials and technological processes for High-Gradient accelerating structures: new results from mechanical tests of an innovative braze-free cavity

Pure oxygen-free high-conductivity copper is a widely used material for manufacturing accelerating cavities working at room temperature. Several studies attempted to explain limitations associated with the maximum allowed field gradients and the behaviour of vacuum RF breakdown in copper accelerating structures through generation and movement of dislocations under stresses associated with RF electric and magnetic fields. Pure copper and also copper alloys undergo mechanical and thermal treatments to be hardened and strengthened during manufacturing, although their mechanical properties significantly change after heating above 590ˆC. High temperature brazing and diffusion bonding are assembly methods widely used to manufacture ultra-high vacuum accelerating devices. However, these processes, occurring at about 800-1000ˆC, significantly affect the mechanical properties of copper and copper alloys. We present here a novel Tungsten Inert Gas welding procedure, which is fast and keeps the high-gradient surfaces of the cavity and other components well below the copper annealing temperature. This process may be successfully used to manufacture copper-based accelerating components. This technology preserves the hardness and cleanliness of copper in order to achieve the maximum accelerating gradient

Radiological dose assessment for the dismantlement and decommissioning option for the Heavy Water Components Test Reactor facility at the Savannah River Site, Aiken, South Carolina

Potential maximum radiation dose rates for a 10,000-year horizon were calculated for the dismantlement and decommissioning option for the Heavy Water Components Test Reactor facility at the Savannah River Site. The residual radioactive material guidelines (RESRAD) computer code was used. The study will help determine if it is acceptable (in terms of DOE radiation dose limits) for activated and contaminated concrete to remain in the facility, along with embedded radioactive piping and radioactive equipment. Four cases were developed to evaluate potential doses; the cases vary with regard to the definitions of the sources. Case A considers the dose from the reactor biological shield; case B considers the dose from contaminated concrete rubble; case C considers the dose from contaminated concrete rubble, the reactor biological shield, and installed equipment; and case D considers the dose from contaminated cuttings brought to the surface following the perforation of a well through the contaminated zone in case C. Site-specific parameter values were used to estimate the radiation doses. The results indicate that neither the DOE dose limit of 100 mrem/yr nor the 15-mrem/yr dose constraint would be exceeded for any of the cases. The potential maximum dose rates for cases A, B, C, and D are 0.000028, 0.015, 0.018, and 0.17 mrem/yr, respectively. The drinking water pathway is the dominant contributor to the doses in cases A through C, and the external gamma pathway is the dominant contributor in case D. Carbon-14, uranium-234, uranium-238, and americium-241 are the principal radionuclides contributing to the doses in cases A through C. Cobalt-60, europium-152, and barium-133 are the important radionuclides in case D. A sensitivity analysis was performed to determine which parameters have the greatest impact on the estimated doses. 9 refs., 11 figs., 3 tabs

British Association for Biological Anthropology and Osteoarchaeology: Equality, Diversity and Inclusion Race Equality Review

Racism continues to be widespread, subtle and often ignored or selectively attended to within organisations. This review sought to evaluate the British Association for Biological Anthropology and Osteoarchaeology (BABAO)’s existing race equality practices, to further support its movement towards becoming an antiracist organisation. The review arose from a commitment by BABAO to interrogate its current structures and redress problematic cultures within the organisation, following a member of colour expressing concerns. In itself, this provides an encouraging example both of the reflexivity of the organisation and the power of a single voice. Through focus groups and surveys, insights were gained with regards to the organisational culture and in response to issues concerning equality, diversity and inclusion (EDI), particularly regarding the need for BABAO to become a more racially literate organisation. The review attempted to glean members’ understanding of anti-racism and how some cultures within the organisation may be racially exclusive or marginalising. In addition to this, the reviewers engaged with stakeholders about where areas could be improved within BABAO in continuing their work towards becoming a racially cognizant organisation. Responses gleaned from the focus groups and survey questionnaire distributed to members revealed that BABAO as an organisation has made some tentative first steps towards race equality, but has some way to go. The paucity of Black, Asian and Minority Ethnic members made gaining perspectives a challenge in relation to experiences of racial discrimination. In itself, this is an indicator that inclusion is an area for growth and reflection. Other key findings included issues with reporting structures and governance processes, with a need for strong and courageous leadership to drive forward conversations around race and racism; a need for training and work to improve racial literacy of the organisation and its members; and a lack of engagement and participation from current members in EDI issues. Nevertheless, the review also indicated that the organisation has made significant strides towards establishing anti-racist practices and are working diligently to engage all members in this endeavour. To this end, the conclusions and recommendations provided aim to enhance current action and further enable BABAO to achieve an anti-racist, inclusive organisational culture.Based on the considerations outlined throughout the report, there were twenty-seven recommendations made. They reflect the need to build a foundation of awareness, understanding and safety upon which to develop a culture of learning, reflection and shared, collective action. High-level recommendations are synthesised below, with further detail in the body of the report

Corrigendum: FLASH Radiotherapy With Electrons: Issues Related to the Production, Monitoring, and Dosimetric Characterization of the Beam

In the original article, the following authors were missing: Luigi Faillace, Lucia Giuliano, Mauro Migliorati, Luigi Palumbo. The corrected Author Contributions statement appears below. Affiliation 3, ‘Sapienza University of Rome, Rome, Italy’, is also added for authors LF, LG, MM, and LP. The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Evaluation of the antioxidant activity of cis/trans-N-phenyl-1,4,4a,5,8,8a-hexahydro-3, 1-benzoxazin-2-imines

The growing interest in the chemistry of unsaturated ring-fused 1,3-heterocycles, in this particular case 1,3-oxazines, arise in part from their versatile pharmacological applications. In the present article, the evaluation of the in vitro and ex vivo antioxidant activity of two cyclohexene-fused oxazines is discussed. The in vitro antioxidant activity was evaluated by trapping the ABTS and hydroxyl radicals as well as the inhibition of the enzyme acetyl-cholinesterase and hemolysis of erythrocytes by 2,2’-Azobis(2-amidinopropane) dihydrochloride (AAPH). The results suggest that both unsaturated 1,3-oxazines are auspicious sources of biologically active compounds with good antioxidant properties. In addition, a comprehensive analysis of the interaction between these heterocycles with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals, as well as the measurements of redox potential, provided evidence for a mechanism of antioxidant activity that takes place through electron transfer (ET) processes.Fil: Firpo, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Ramirez, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: de Brito, Maria Dos R. Mendes. Universidade Federal Do Piaui.; BrasilFil: Silva, Ana P. S. Correia Lima E.. Universidade Federal Do Piaui.; BrasilFil: Costa, Jessica Pereira. Universidade Federal Do Piaui.; BrasilFil: Rodríguez, Marcela C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Argüello, Gustavo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Szakonyi, Zsolt. Institute Of Pharmaceutical Chemistry Albert Szent-györ; HungríaFil: Fülöp, Ferenc. Institute Of Pharmaceutical Chemistry Albert Szent-györ; HungríaFil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Two-pass two-way acceleration in a superconducting continuous wave linac to drive low jitter x-ray free electron lasers

We present a design study of an innovative scheme to generate high rep rate (MHz-class) GeV electron beams by adopting a two-pass two-way acceleration in a Superconducting (SC) linac operated in Continuous Wave (CW) mode. The electron beam is accelerated twice by being re-injected in opposite direction of propagation into the linac after the first passage. Acceleration in opposite directions is accomplished thanks to standing waves supported in RF cavities. The task of recirculating the electron beam when it leaves the linac after first pass is performed by a Bubble-shaped Arc Compressor composed by a sequence of Double Bend Achromat. In this paper we address the main issues inherent to the two-pass acceleration process and the preservation of the electron beam quality parameters (emittance, energy spread, peak current) required to operate X-ray Free Electron Lasers with low jitters in the amplitude, spectral and temporal domain, as achieved by operating in seeding and/or oscillator mode a CW FEL up to 1 MHz rep rate. Detailed start-to-end simulations are shown to assess the capability of this new scheme to double the electron beam energy as well as to compress the electron bunch length from picoseconds down to tens of femtoseconds. The advantage of such a scheme is to halve the requested linac length for the same final electron beam energy, which is typically in the few GeV range, as needed to drive an X-ray FEL. The AC power to supply the cryogenic plant is also significantly reduced with respect to a conventional single-pass SC linac for the same final energy. We are reporting also X-ray FEL simulations for typical values of wavelengths of interest (in the 200 eV \u2013 8 keV photon energy range) to better illustrate the potentiality of this new scheme

High field hybrid photoinjector electron source for advanced light source applications

The production of high spectral brilliance radiation from electron beam sources depends critically on the electron beam qualities. One must obtain very high electron beam brightness, implying simultaneous high peak current and low emittance. These attributes are enabled through the use of very high field acceleration in a radio-frequency (rf) photoinjector source. Despite the high fields currently utilized, there is a limit on the achievable peak current in high brightness operation, in the range of tens of Ampere. This limitation can be overcome by the use of a hybrid standing wave/traveling wave structure; the standing wave portion provides acceleration at a high field from the photocathode, while the traveling wave part yields strong velocity bunching. This approach is explored here in a C-band scenario, at field strengths (&gt;100 MV/m) at the current state-of-the-art. It is found that one may arrive at an electron beam with many hundreds of Amperes with well-sub-micron normalized emittance. This extremely compact injector system also possesses attractive simplification of the rf distribution system by eliminating the need for an rf circulator. We explore the use of this device in a compact 400 MeV-class source, driving both inverse Compton scattering and free-electron laser radiation sources with unique, attractive properties

Do antibiotic-impregnated shunts in hydrocephalus therapy reduce the risk of infection? An observational study in 258 patients

<p>Abstract</p> <p>Background</p> <p>Shunt infection in hydrocephalus patients is a severe, even life-threatening complication. Antibiotic-impregnated shunts (AIS) have been developed in an attempt to reduce rate of shunt infection. The study was performed to analyze if AIS can diminish the rate of shunt infection. The pathogenic nature of shunt infection in patients with AIS systems and those without antibiotic impregnated shunts (non-AIS) was compared.</p> <p>Methods</p> <p>Over a period of 24 months in the Department of Neurosurgery at University Hospital of Tübingen shunt surgery was performed in 258 patients. In 86 patients AIS systems were implanted. Shunt catheters were commercially impregnated with clindamycin and rifampicin. Analysis of the clinical data included sex, age, classification of hydrocephalus, shunt types and risk factors for shunt infection [age (< 1 year and > 80 years), prematurely born patients, external ventricular drainage, former shunt infection, former systemic infection, disturbance of consciousness, former radiation-/chemotherapy]. Infection rates and underlying bacterial pathogens of patients with AIS were compared to patients with implanted non-AIS systems (172 patients).</p> <p>Results</p> <p>AIS and non-AIS patients did not differ in sex, etiology of hydrocephalus and the shunt type. In the AIS group 72 out of 86 patients had at least one risk factor (83.7 %), compared to 126 patients in the non-AIS group (73.3 %). There was no significant difference between the two groups (p = 0.0629; Fisher's exact test). In patients with no risk factors, only one patient with non-AIS suffered from shunt infection. In patients with one or more risk factors the rate for shunt infection was 7.14 % in patients with non-AIS and 6.94 % in patients with AIS. Former shunt infection (p = 0.0124) was related to higher risk for shunt infection. The use of AIS had therefore no significant advantage (p = 0.8611; multiple logistic regression).</p> <p>Significantly related to a shunt infection was the number of shunt surgeries. 190 interventions in the AIS group (2.21 interventions per patient) and 408 in the non-AIS group (2.37 interventions per patient) had been performed (p = 0.3063; Wilcoxon). There was no shunt infection in the group of patients on whom only one shunt surgery was performed. In patients with at least two shunt surgeries the infection rate was 9%. The infection rate in AIS patients was 5/52 (9.6 %) and in the non-AIS 10/114 (8.77 %), (p = 1.0; Fisher's exact test). Staphylococcus epidermidis was the most frequent pathogen for shunt infection. Fourteen out of 15 infections occurred within the first 6 months of surgery. The most frequent pathogen for shunt infection was S. epidermidis. No toxic or allergic complications were seen using the AIS shunt systems. The presented data show a remarkably low infection rate of 5.8 % in the non-AIS group compared to other studies which demonstrated a significant decrease in the infection rate by AIS.</p> <p>Conclusion</p> <p>AIS did not significantly reduce shunt infection in hydrocephalus patients in the presented study. In the AIS group three patients suffered from shunt infections caused by skin ulceration or neurosurgical procedures with exposure of the cerebrospinal liquor after shunt implantation. AIS was not developed to prevent infection in such cases, therefore an advantage of AIS can not be excluded. In view of the presented data and the small number of reported studies a prospective randomized multicenter study is required.</p

Variation in dental morphology and inference of continental ancestry in admixed Latin Americans

Objectives: To investigate the variation in dental nonmetric traits and to evaluate the utility of this variation for inferring genetic ancestry proportions in a sample of admixed Latin Americans. Materials and Methods: We characterized a sample from Colombia (N = 477) for 34 dental traits and obtained estimates of individual Native American, European, and African ancestry using genome‐wide SNP data. We tested for correlation between dental traits, genetic ancestry, age, and sex. We carried out a biodistance analysis between the Colombian sample and reference continental population samples using the mean measure of divergence statistic calculated from dental trait frequencies. We evaluated the inference of genetic ancestry from dental traits using a regression approach (with 10‐fold cross‐validation) as well as by testing the correlation between estimates of ancestry obtained from genetic and dental data. Results: Latin Americans show intermediate dental trait frequencies when compared to Native Americans, Europeans, and Africans. Significant correlations were observed for several dental traits, genetic ancestry, age, and sex. The biodistance analysis displayed a closer relationship of Colombians to Europeans than to Native Americans and Africans. Mean ancestry estimates obtained from the dental data are similar to the genetic estimates (Native American: 32% vs. 28%, European: 59% vs. 63%, and African: 9% vs. 9%, respectively). However, dental features provided low predictive power for genetic ancestry of individuals in both approaches tested (R2 < 5% for all genetic ancestries across methods). Discussion: The frequency of dental traits in Latin Americans reflects their admixed Native American, European and African ancestry and can provide reasonable average estimates of genetic ancestry. However, the accuracy of individual genetic ancestry estimates is relatively low, probably influenced by the continental differentiation of dental traits, their genetic architecture, and the distribution of genetic ancestry in the individuals examined