Pan-azole- and multi-fungicide-resistant Aspergillus fumigatus is widespread in the United States.

Aspergillus fumigatus is an important global fungal pathogen of humans. Azole drugs are among the most effective treatments for A. fumigatus infection. Azoles are also widely used in agriculture as fungicides against fungal pathogens of crops. Azole-resistant A. fumigatus has been increasing in Europe and Asia for two decades where clinical resistance is thought to be driven by agricultural use of azole fungicides. The most prevalent mechanisms of azole resistance in A. fumigatus are tandem repeats (TR) in the cyp51A promoter coupled with mutations in the coding region which result in resistance to multiple azole drugs (pan-azole resistance). Azole-resistant A. fumigatus has been isolated from patients in the United States (U.S.), but little is known about its environmental distribution. To better understand the distribution of azole-resistant A. fumigatus in the U.S., we collected isolates from agricultural sites in eight states and tested 202 isolates for sensitivity to azoles. We found azole-resistant A. fumigatus in agricultural environments in seven states showing that it is widespread in the U.S. We sequenced environmental isolates representing the range of U.S. sample sites and compared them with publicly available environmental worldwide isolates in phylogenetic, principal component, and ADMIXTURE analyses. We found worldwide isolates fell into three clades, and TR-based pan-azole resistance was largely in a single clade that was strongly associated with resistance to multiple agricultural fungicides. We also found high levels of gene flow indicating recombination between clades highlighting the potential for azole-resistance to continue spreading in the U.S.IMPORTANCEAspergillus fumigatus is a fungal pathogen of humans that causes over 250,000 invasive infections each year. It is found in soils, plant debris, and compost. Azoles are the first line of defense antifungal drugs against A. fumigatus. Azoles are also used as agricultural fungicides to combat other fungi that attack plants. Azole-resistant A. fumigatus has been a problem in Europe and Asia for 20 years and has recently been reported in patients in the United States (U.S.). Until this study, we did not know much about azole-resistant A. fumigatus in agricultural settings in the U.S. In this study, we isolated azole-resistant A. fumigatus from multiple states and compared it to isolates from around the world. We show that A. fumigatus which is resistant to azoles and to other strictly agricultural fungicides is widespread in the U.S.

Newly emerging therapies for neonatal seizures.

The treatment of neonatal seizures has not changed significantly over the last 50 years despite advances in antiepileptic drug (AED) development for older children and adults. Recently new drugs have emerged some of which address age-specific challenges or mechanisms and will be discussed in this review. The loop diuretic bumetanide blocks the neuronal NKCC1 co-transporter and is thought specifically to supress seizures in the immature brain. Levetiracetam has been used in children and infants with good efficacy, an excellent safety profile, and near-ideal pharmacokinetic characteristics. Randomised controlled trials are now underway to test the efficacy of some newer AEDs for neonatal seizures. Topiramate has been shown to have neuroprotective properties in addition to its antiepileptic action and trials in babies with hypoxic-ischaemic encephalopathy are now planned. There is an urgent need to develop age-specific AEDs for preterm and term babies. These drugs must be evaluated with multicentre, collaborative trials using innovative methods and high ethical standards to overcome age-specific challenges with the ultimate aim of improving the outcome for neonates with seizures.

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures.

OBJECTIVE: The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis. STUDY DESIGN: We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann-Whitney, Kruskal-Wallis or Fisher's exact tests where appropriate. RESULTS: Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida. CONCLUSION: Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.

The Kelvin and Temperature Measurements.

The International Temperature Scale of 1990 (ITS-90) is defined from 0.65 K upwards to the highest temperature measurable by spectral radiation thermometry, the radiation thermometry being based on the Planck radiation law. When it was developed, the ITS-90 represented thermodynamic temperatures as closely as possible. Part I of this paper describes the realization of contact thermometry up to 1234.93 K, the temperature range in which the ITS-90 is defined in terms of calibration of thermometers at 15 fixed points and vapor pressure/temperature relations which are phase equilibrium states of pure substances. The realization is accomplished by using fixed-point devices, containing samples of the highest available purity, and suitable temperature-controlled environments. All components are constructed to achieve the defining equilibrium states of the samples for the calibration of thermometers. The high quality of the temperature realization and measurements is well documented. Various research efforts are described, including research to improve the uncertainty in thermodynamic temperatures by measuring the velocity of sound in gas up to 800 K, research in applying noise thermometry techniques, and research on thermocouples. Thermometer calibration services and high-purity samples and devices suitable for "on-site" thermometer calibration that are available to the thermometry community are described. Part II of the paper describes the realization of temperature above 1234.93 K for which the ITS-90 is defined in terms of the calibration of spectroradiometers using reference blackbody sources that are at the temperature of the equilibrium liquid-solid phase transition of pure silver, gold, or copper. The realization of temperature from absolute spectral or total radiometry over the temperature range from about 60 K to 3000 K is also described. The dissemination of the temperature scale using radiation thermometry from NIST to the customer is achieved by calibration of blackbody sources, tungsten-strip lamps, and pyrometers. As an example of the research efforts in absolute radiometry, which impacts the NIST spectral irradiance and radiance scales, results with filter radiometers and a high-temperature blackbody are summarized.

Special Report on the International Temperature Scale of 1990: Report on the 17th Session of the Consultative Committee on Thermometry.

This article summarizes the results of the 17th Session of the Consultative Committee on Thermometry of the International Committee of Weights and Measures (Comité Consultatif de Thermométrie of the Comité International des Poids et Mesures) that met in Sèvres, France, September 12-14, 1989. That session was devoted exclusively to the completion of the International Temperature Scale of 1990, described herein, and to the implications of its adoption.

The new International Temperature Scale of 1990 (ITS-90).

A new international temperature scale, the ITS-90, will replace the International Practical Temperature Scale of 1968 (amended edition of 1975), IPTS-68(75), on 1 January 1990. Temperatures on the ITS-90 will agree more closely with thermodynamic temperatures; therefore, the ITS-90 represents a substantial improvement over the IPTS-68(75). Fortunately for the clinical laboratory community, the change in the scale will be at most only 0.05 degrees C or less in the range from 0 to 60 degrees C, but corrections in primary calibrations should be made so that the calibrations are based on the ITS-90.

SRM 1970: Succinonitrile Triple-Point Standard-A Temperature Reference Standard Near 58.08 °C.

Triple-point-of-succinonitrile cells have been tested and established as Standard Reference Material (SRM) 1970. Of the 115 cells tested, 109 were accepted as SRM 1970. Five of the 115 cells had triple-point temperatures lower than 58.0785 °C (the low-temperature limit established for SRM 1970) and, consequently, were rejected. One of the 115 cells broke during tests on it. The mean value of the triple-point temperatures (obtained by freezing) of the 109 cells is 58.0796±0.0015 °C, where the uncertainty is the total estimated uncertainty relative to the International Practical Temperature Scale of 1968, Amended Edition of 1975. The standard deviation of the triple-point temperatures is 0.48 mK. The purity of the succinonitrile of the SRM 1970 cells is estimated to range from 99.999,97% to 99.999,84%. The preparation of the cells, the various tests performed on them, and the procedure recommended for their use are described.

Stability of Small Industrial Platinum Resistance Thermometers.

This paper reports the results of an investigation of the stability of a selection of small industrial platinum resistance thermometers (IPRTs) upon heat treatment and handling. Ninety-four IPRTs, of several models, obtained from five manufacturers were studied. Most of the IPRTs exhibited calibration drifts and also effects due to the presence of moisture or strain. There was no apparent improvement in the stability if the resistance ratio, R(t)/R 0= W(t), instead of resistance were used as the criterion. Comparisons are made of the relative stability of the products of the five companies.

The succinonitrile triple-point standard: a fixed point to improve the accuracy of temperature measurements in the clinical laboratory.

In an investigation of the melting and freezing behavior of succinonitrile, the triple-point temperature was determined to be 58.0805 degrees C, with an estimated uncertainty of +/- 0.0015 degrees C relative to the International Practical Temperature Scale of 1968 (IPTS-68). The triple-point temperature of this material is evaluated as a temperature-fixed point, and some clinical laboratory applications of this fixed point are proposed. In conjunction with the gallium and ice points, the availability of succinonitrile permits thermistor thermometers to be calibrated accurately and easily on the IPTS-68.

Report on the Sixth International Symposium on Temperature.

This is a report on the Sixth International Symposium of Temperature which was held in Washington, DC, USA, March 15-18, 1982. Included is a brief introduction discussing the timeliness of the symposium, its sponsors, and the publication of the proceedings. The remainder of the report is devoted to a summary of the Plenary and Technical sessions of the symposium.

Transition Temperatures of the Hydrates of Na2SO4, Na2HPO4, and KF as Fixed Points in Biomedical Thermometry.

The hydrate transition temperatures of Na2SO4·10H2O to Na2SO4, KF·2H2O to KF, and Na2HPO4·7H2O to Na2HPO4·2H2O were established using ACS grade salts as 32.374 °C, 41.422 °C, and 48.222 °C, respectively. A simple and reliable procedure involving inexpensive materials was used to realize these transitions as temperature fixed points. Each transition temperature was attained within 30 minutes of hydrate initiation and remained constant to within ±0.002 °C for more than 10 hours if the mixture was stirred. The established transition temperatures were sensitive at the 0.001 °C level to the amount of impurities, so the materials used should be of the highest quality available. These systems fill a gap in the existing spectrum of temperature standards and should be useful in biomedical laboratories for calibrating thermometers.

Modification of cell membrane lipids in Micrococcus lysodeikticus induced by pantoyl lactone.

Growth of Microccoccus lysodeikticus in the presence of pantoyl lactone brings about both qualitative and quantitative changes in cell membrane lipids. Significant amounts of the two major phospholipids (phosphatidylglycerol and diphosphatidylglycerol) are converted to lyso forms; the largest conversion occurs in the phosphatidylglycerol. In addition, amounts of several phospholipid fatty acids are changed. Physical alteration of the call membrane can be demonstrated using differential scanning calorimetry. Although growth and transport are significantly inhibited when pantoyl lactone is present, cells possessing altered call membrane phospholipds and phospholipid fatty acids, brought about by growth in the presence of pantoyl lactone, transport D-alanine, L-glutamic and L-aspartic acid normally when washed free of the pantoyl lactone.

An Investigation of the Stability of Thermistors.

In order to better characterize thermistors, a group of 405 bead-in-glass and disc thermistors were aged in constant temperature baths. Samples of 135 thermistors were aged in each of three constant temperature baths held at 0, 30, and 60 °C. Each sample was composed of 65 bead-in-glass and 70 disc thermistors which represented a total of six manufacturers and six resistance values. The thermistors were maintained at temperature for 550 to 770 days and their resistances and the bath temperatures were periodically monitored. Analysis of the data revealed systematic differences between bead-in-glass and disc thermistors upon ageing and indicated a dependence of ageing behavior on bath temperature and resistance value. Drift rates within groups of thermistors from each manufacturer were fairly uniform. Large initial changes in the drift rate for the disc thermistors at 30 and 60 °C (and to a much lesser extent in the bead-in-glass thermistors) require that thermistors for use at an accuracy level of a few tens of millikelvins be aged prior to use.

The gallium melting-point standard: its role in our temperature measurement system.

The latest internationally-adopted temperature scale, the International Practical Temperature Scale of 1968 (amended edition of 1975), is discussed in some detail and a brief description is given of its evolution. The melting point of high-purity gallium (stated to be at least 99.99999% pure) as a secondary temperature reference point is evaluated. I believe that this melting-point temperature of gallium should be adopted by the various medical professional societies and voluntary standards groups as the reaction temperature for enzyme reference methods in clinical enzymology. Gallium melting-point cells are available at the National Bureau of Standards as Standard Reference Material No. 1968.