Human endometrial carcinomas serially transplanted in nude mice and established in continuous cell lines.

Three out of five human endometrial carcinomas were successfully grafted into nude mice (BALB/c/nu/nu). Two of these tumors could be maintained by serial transplantation. The morphological characteristics displayed by the grafted tumors were comparable to those of the original carcinomas. Permanent cell lines were established from these two tumors. Reinjection of cells grown in vitro into nude mice produced nodules of identical histology as compared to original solid transplants. The influence of medroxyprogesterone acetate on tumor growth in vivo and cell proliferation in vitro was studied. This hormonal treatment did not produce any significant effect on tumor cells, either in vitro or in vivo, for the two endometrial carcinomas. After medroxyprogesterone administration, a slight but non-significant growth inhibition of the tumor cells in vitro was observed and the tumor transplants in vivo did not appear to be influenced. The experiments illustrate the possible use of this model for testing potential anti-cancer agents.

A continuous strain-space model of viral evolution within a host

Viruses rapidly evolve, and HIV in particular is known to be one of the fastest evolving human viruses. It is now commonly accepted that viral evolution is the cause of the intriguing dynamics exhibited during HIV infections and the ultimate success of the virus in its struggle with the immune system. To study viral evolution, we use a simple mathematical model of the within-host dynamics of HIV which incorporates random mutations. In this model, we assume a continuous distribution of viral strains in a one-dimensional phenotype space where random mutations are modelled by di ffusion. Numerical simulations show that random mutations combined with competition result in evolution towards higher Darwinian fitness: a stable traveling wave of evolution, moving towards higher levels of fi tness, is formed in the phenoty space.

Drug assessment by a Pharmacy and Therapeutics committee: from drug selection criteria to use in clinical practice.

BACKGROUND In Spain, hospital medicines are assessed and selected by local Pharmacy and Therapeutics committees (PTCs). Of all the drugs assessed, cancer drugs are particularly important because of their budgetary impact and the sometimes arguable added value with respect to existing alternatives. This study analyzed the PTC drug selection process and the main objective was to evaluate the degree of compliance of prescriptions for oncology drugs with their criteria for use. METHODS This was a retrospective observational study (May 2007 to April 2010) of PTC-assessed drugs. The variables measured to describe the committee's activity were number of drugs assessed per year and number of drugs included in any of these settings: without restrictions, with criteria for use, and not included in formulary. These drugs were also analyzed by therapeutic group. To assess the degree of compliance of prescriptions, a score was calculated to determine whether prescriptions for bevacizumab, cetuximab, trastuzumab, and bortezomib were issued in accordance with PTC drug use criteria. RESULTS The PTC received requests for inclusion of 40 drugs, of which 32 were included in the hospital formulary (80.0%). Criteria for use were established for 28 (87.5%) of the drugs included. In total, 293 patients were treated with the four cancer drugs in eight different therapeutic indications. The average prescription compliance scores were as follows: bevacizumab, 83% for metastatic colorectal cancer, 100% for metastatic breast cancer, and 82.3% for non-small-cell lung cancer; cetuximab, 62.0% for colorectal cancer and 50% for head and neck cancer; trastuzumab, 95.1% for early breast cancer and 82.4% for metastatic breast cancer; and bortezomib, 63.7% for multiple myeloma. CONCLUSION The degree of compliance with criteria for use of cancer drugs was reasonably high. PTC functions need to be changed so that they can carry out more innovative tasks, such as monitoring conditions for drug use.

Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

BACKGROUND & AIMS Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF.

Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM.

OBJECTIVES: Recommendations for EEG monitoring in the ICU are lacking. The Neurointensive Care Section of the ESICM assembled a multidisciplinary group to establish consensus recommendations on the use of EEG in the ICU. METHODS: A systematic review was performed and 42 studies were included. Data were extracted using the PICO approach, including: (a) population, i.e. ICU patients with at least one of the following: traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, stroke, coma after cardiac arrest, septic and metabolic encephalopathy, encephalitis, and status epilepticus; (b) intervention, i.e. EEG monitoring of at least 30 min duration; (c) control, i.e. intermittent vs. continuous EEG, as no studies compared patients with a specific clinical condition, with and without EEG monitoring; (d) outcome endpoints, i.e. seizure detection, ischemia detection, and prognostication. After selection, evidence was classified and recommendations developed using the GRADE system. RECOMMENDATIONS: The panel recommends EEG in generalized convulsive status epilepticus and to rule out nonconvulsive seizures in brain-injured patients and in comatose ICU patients without primary brain injury who have unexplained and persistent altered consciousness. We suggest EEG to detect ischemia in comatose patients with subarachnoid hemorrhage and to improve prognostication of coma after cardiac arrest. We recommend continuous over intermittent EEG for refractory status epilepticus and suggest it for patients with status epilepticus and suspected ongoing seizures and for comatose patients with unexplained and persistent altered consciousness. CONCLUSIONS: EEG monitoring is an important diagnostic tool for specific indications. Further data are necessary to understand its potential for ischemia assessment and coma prognostication.

Médecines complémentaires: vers un consensus "evidence-based" à l'hôpital universitaire. [Complementary and alternative medicines (CAM): towards an "evidence-based" consensus in the University hospital]

Après la votation fédérale demandant de prendre en compte les médecines complémentaires, un consensus a été recherché dans quatorze services et unités du Centre hospitalier universitaire vaudois (CHUV). Confrontés aux données de la littérature (Plus de 2000 publications en "Evidence-based complementary medicine" depuis 1998), les soignants étaient tous surpris par l'ampleur des résultats cliniques disponibles actuellement. Tous identifiaient un besoin en formation et en informations sur le sujet. Une prise de position officielle de l'institution était aussi souhaitée, instituant l'enseignement et la recherche sur les médecines complémentaires et assurant la production d'informations rigoureuses et pertinentes pour la clinique. [Abstract] While a popular vote supported a new article on complementary and alternative medicines (CAM) in the Swiss Constitution, this assessment in 14 wards of the University Hospital of Lausanne, Switzerland, attempted at answering the question: How can CAM use be better taken into account and patients informed with more rigor and respect for their choices? Confronted with a review of the literature (> 2000 publications in "Evidence-based cornplementary medicine" since 1998), respondents declared their ignorance of the clinical data presently available on CAM. All were in favour of more teaching and information on the subject, plus an official statement from the Hospital direction, ensuring production and diffusion of rigorous and cJinically significant information on CAM.

Optimum pilot overhead in wireless communication: a unified treatment of continuous and block-fading channels

The optimization of the pilot overhead in wireless fading channels is investigated, and the dependence of this overhead on various system parameters of interest (e.g., fading rate, signal-to-noise ratio) is quantified. The achievable pilot-based spectral efficiency is expanded with respect to the fading rate about the no-fading point, which leads to an accurate order expansion for the pilot overhead. This expansion identifies that the pilot overhead, as well as the spectral efficiency penalty with respect to a reference system with genie-aided CSI (channel state information) at the receiver, depend on the square root of the normalized Doppler frequency. It is also shown that the widely-usedblock fading model is a special case of more accurate continuous fading models in terms of the achievable pilot-based spectral efficiency. Furthermore, it is established that the overhead optimization for multiantenna systems is effectively the same as for single-antenna systems with thenormalized Doppler frequency multiplied by the number of transmit antennas.

Managers' perspective on continuous health education in a region of São Paulo State

OBJECTIVEAnalysing the concepts of Continuous Health Education - CHE (EPS - in Portuguese), operated by municipal managers and translated into official documents.METHODQualitative research with the use of official documents and semi-structured interviews with the Municipal Health Secretaries or Coordinators of Primary Health Care in the Northeast Region of São Paulo State, and thematic analysis of empirical material.RESULTSResults indicate difficulties in the municipalities problematizing their management practices, services and health care; EPS tools presented are insufficient and unsatisfactory for amending the array of problems raised and are still far from the routine of Primary Care services.CONCLUSIONDespite efforts to implement EPS actions for the strengthening of primary care, the process appears to be incipient.

Ignoring information in binary choice with continuous variables: When is less 'more'?

When can a single variable be more accurate in binary choice than multiple sources of information? We derive analytically the probability that a single variable (SV) will correctly predict one of two choices when both criterion and predictor are continuous variables. We further provide analogous derivations for multiple regression (MR) and equal weighting (EW) and specify the conditions under which the models differ in expected predictive ability. Key factors include variability in cue validities, intercorrelation between predictors, and the ratio of predictors to observations in MR. Theory and simulations are used to illustrate the differential effects of these factors. Results directly address why and when one-reason decision making can be more effective than analyses that use more information. We thus provide analytical backing to intriguing empirical results that, to date, have lacked theoretical justification. There are predictable conditions for which one should expect less to be more.

Continuous phase shift of sinusoidal signals using injection locked oscillators

This work presents an alternative to generate continuous phase shift of sinusoidal signals based on the use of super harmonic injection locked oscillators (ILO). The proposed circuit is a second harmonic ILO with varactor diodes as tuning elements. In the locking state, by changing the varactor bias, a phase shift instead of a frequency shift is observed at the oscillator output. By combining two of these circuits, relative phases up to 90 could be achieved. Two prototypes of the circuit have been implemented and tested, a hybrid version working in the range of 200-300 MHz and a multichip module (MCM) version covering the 900¿1000 MHz band.

Nitrogen fertilizer use efficiency, recovery and leaching of an alexandergrass pasture

Nitrogen usually determines the productive potential of forage crops, although it is highly unstable in the environment. Studies on recovery rates and use efficiency are important for more reliable fertilizer recommendations to reduce costs and avoid environmental pollution. The purpose of this study was to evaluate N use efficiency and recovery rate of Alexandergrass pasture (Brachiaria - Syn. Urochloa plantaginea) as well as N-NO3- and N-NH4+ soil concentrations using different levels of N fertilization under two grazing intensities. The experiment was arranged in a randomized block design in a factorial scheme with three replications. Treatments consisted of three N rates (0, 200 and 400 kg ha-1 N) and two grazing intensities termed low mass (LM; forage mass of 2,000 kg ha-1 of DM) and high mass (HM; forage mass of 3,600 kg ha-1 of DM) under continuous stocking and variable stocking rates. Results of N fertilization with 200 kg ha-1 were better than with 400 kg ha-1 N. There was a significant effect of N rates on soil N-NO3-concentration with higher levels in the first layer of the soil profile in the treatment with 400 kg ha-1 N. Grazing intensity also affected soil N-NO3- concentration, by increasing the levels under the higher stocking rate (lower forage mass).

The effects of land use and soil management on the physical properties of an Oxisol in Southeast Brazil

Soils of the tropics are prone to a decrease in quality after conversion from native forest (FO) to a conventional tillage system (CT). However, the adoption of no-tillage (NT) and complex crop rotations may improve soil structural quality. Thus, the aim of this study was to evaluate the physical properties of an Oxisol under FO, CT, and three summer crop sequences in NT: continuous corn (NTcc), continuous soybean (NTcs), and a soybean/corn rotation (NTscr). Both NT and CT decreased soil organic carbon (SOC) content, SOC stock, water stable aggregates (WSA), geometric mean diameter (GMD), soil total porosity (TP), macroporosity (MA), and the least limiting water range (LLWR). However they increased soil bulk density (BD) and tensile strength (TS) of the aggregates when compared to soil under FO. Soil under NT had higher WSA, GMD, BD, TS and microporosty, but lower TP and MA than soil under CT. Soil under FO did not attain critical values for the LLWR, but the lower limit of the LLWR in soils under CT and NT was resistance to penetration (RP) for all values of BD, while the upper limit of field capacity was air-filled porosity for BD values greater than 1.46 (CT), 1.40 (NTscr), 1.42 (NTcc), and 1.41 (NTcs) kg dm-3. Soil under NTcc and NTcs decreased RP even with the increase in BD because of the formation of biopores. Furthermore, higher critical BD was verified under NTcc (1.62 kg dm-3) and NTcs (1.57 kg dm-3) compared to NTscr and CT (1.53 kg dm-3).

Preparation, maintenance, and use of serum-free aggregating brain cell cultures.

Serum-free aggregating brain cell cultures are free-floating three-dimensional primary cell cultures able to reconstitute spontaneously a histotypic brain architecture to reproduce critical steps of brain development and to reach a high level of structural and functional maturity. This culture system offers, therefore, a unique model for neurotoxicity testing both during the development and at advanced cellular differentiation, and the high number of aggregates available combined with the excellent reproducibility of the cultures facilitates routine test procedures. This chapter presents a detailed description of the preparation, maintenance, and use of these cultures for neurotoxicity studies and a comparison of the developmental characteristics between cultures derived from the telencephalon and cultures derived from the whole brain. For culture preparation, mechanically dissociated embryonic brain tissue is used. The initial cell suspension, composed of neural stem cells, neural progenitor cells, immature postmitotic neurons, glioblasts, and microglial cells, is kept in a serum-free, chemically defined medium under continuous gyratory agitation. Spherical aggregates form spontaneously and are maintained in suspension culture for several weeks. Within the aggregates, the cells rearrange and mature, reproducing critical morphogenic events, such as migration, proliferation, differentiation, synaptogenesis, and myelination. For experimentation, replicate cultures are prepared by the randomization of aggregates from several original flasks. The high yield and reproducibility of the cultures enable multiparametric endpoint analyses, including "omics" approaches.

Strengthening of an Existing Continuous-Span, Steel-Beam, Concrete-Deck Bridge by Post-Tensioning, HR-308, 1990

The need to upgrade a large number of understrength and obsolete bridges in the U.S. has been well documented in the literature. Through several Iowa DOT projects, the concept of strengthening simple-span bridges by post-tensioning has been developed. The purpose of the project described in this report was to investigate the use of post-tensioning for strengthening continuous composite bridges. In a previous, successfully completed investigation, the feasibility of strengthening continuous, composite bridges by post-tensioning was demonstrated on a laboratory 1/3-scale-model bridge (3 spans: 41 ft 11 in. x 8 ft 8 in.). This project can thus be considered the implementation phase. The bridge selected for strengthening was in Pocahontas County near Fonda, Iowa, on County Road N28. With finite element analysis, a post-tensioning system was developed that required post-tensioning of the positive moment regions of both the interior and exterior beams. During the summer of 1988, the strengthening system was installed along with instrumentation to determine the bridge's response and behavior. Before and after post-tensioning, the bridge was subjected to truck loading (1 or 2 trucks at various predetermined critical locations) to determine the effectiveness of the strengthening system. The bridge, with the strengthening system in place, was inspected approximately every three months to determine any changes in its appearance or behavior. In 1989, approximately one year after the initial strengthening, the bridge was retested to identify any changes in its behavior. Post-tensioning forces were removed to reveal any losses over the one-year period. Post-tensioning was reapplied to the bridge, and the bridge was tested using the same loading program used in 1988. Except for at a few locations, stresses were reduced in the bridge the desired amount. At a few locations flexural stresses in the steel beams are still above 18 ksi, the allowable inventory stress for A7 steel. Although maximum stresses are above the inventory stress by about 2 ksi, they are about 5 ksi below the allowable operating stress; therefore, the bridge no longer needs to be load-posted.