A reverse engineering approach to the suppression of citation biases reveals universal properties of citation distributions

The large amount of information contained in bibliographic databases has recently boosted the use of citations, and other indicators based on citation numbers, as tools for the quantitative assessment of scientific research. Citations counts are often interpreted as proxies for the scientific influence of papers, journals, scholars, and institutions. However, a rigorous and scientifically grounded methodology for a correct use of citation counts is still missing. In particular, cross-disciplinary comparisons in terms of raw citation counts systematically favors scientific disciplines with higher citation and publication rates. Here we perform an exhaustive study of the citation patterns of millions of papers, and derive a simple transformation of citation counts able to suppress the disproportionate citation counts among scientific domains. We find that the transformation is well described by a power-law function, and that the parameter values of the transformation are typical features of each scientific discipline. Universal properties of citation patterns descend therefore from the fact that citation distributions for papers in a specific field are all part of the same family of univariate distributions.Comment: 9 pages, 6 figures. Supporting information files available at http://filrad.homelinux.or

Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes

Improvement in medication education in a pediatric subspecialty practice

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to measure the impact of an educational intervention on parents of children taking methotrexate (MTX) for juvenile idiopathic arthritis (JIA).</p> <p>Methods</p> <p>This study was conducted using a pre- and postsurvey design. The parents of 100 children with JIA taking MTX for at least 2 months were surveyed during a routine office visit. The parents completed an initial questionnaire regarding the safe use, adverse effects, and guidelines for monitoring the toxicity of MTX. An educational intervention was then administered, and an identical follow-up questionnaire was given during the next office visit. Statistical analysis using a paired <it>t</it>-test (critical <it>P </it>value < 0.05) was performed on individuals who answered both questionnaires.</p> <p>Results</p> <p>There were 100 responses to the initial questionnaire and 67 responses to the follow-up questionnaire. The mean length of time between surveys was 2.9 ± 0.9 months. In those who completed both questionnaires, the overall correct score increased significantly from 75.8% to 93.4%, respectively (<it>P </it>< 0.0001). Individuals scored the lowest (49%) on the question that addressed MTX's impact on pregnancy and fertility.</p> <p>Conclusions</p> <p>MTX knowledge may be less than expected in the parents of children with JIA. Brief educational interventions in the pediatric subspecialty practice can significantly affect a family's understanding of their child's medications.</p

Swab-yourself trial with economic monitoring and testing for infections collectively (SYSTEMATIC): Part 2. A diagnostic accuracy, and cost-effectiveness, study comparing rectal, pharyngeal and urogenital samples analysed individually, versus as a pooled specimen, for the diagnosis of gonorrhoea and chlamydia

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordBACKGROUND: Sexual history does not accurately identify those with extragenital Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) so universal extragenital sampling is recommended. Nucleic acid amplification tests (NAATs) are expensive. If urogenital, plus rectal and pharyngeal, samples are analysed the diagnostic cost is trebled. Pooling samples into one NAAT container would cost the same as urogenital samples alone. We compared clinician triple samples analysed individually with self-taken pooled samples for diagnostic accuracy, and cost, in MSM and females. METHODS: Prospective, convenience, sample in UK sexual health clinic. Randomised order of clinician and self-samples from pharynx, rectum, plus first catch urine (FCU) in MSM and vulvovaginal swabs (VVS) in females, for NG and CT detection. RESULTS: Of 1793 participants (1284 females, 509 MSM), 116 had NG detected (75 urogenital, 83 rectum, 72 pharynx). 276 had CT detected (217 urogenital, 249 rectum, 63 pharynx).There was no difference in sensitivities between clinician triple samples and self-pooled specimens for NG (99.1%, 98.3%) but clinician samples analysed individually identified 3% more chlamydia infections than pooled (99.3%, 96.0%; p=0.027). However, pooled specimens identified more infections than VVS/FCU alone. Pooled specimens missed 2 NG and 11 CT infections, whereas VVS/FCU missed 41 NG and 58 CT infections. Self-taken pooled specimens were the most cost-effective. CONCLUSIONS: Just FCU/VVS testing missed many infections. Self-taken pooled samples were as sensitive as clinician triple samples for identifying NG, but clinician samples analysed individually identified 3% more CT infections than pooled. The extragenital sampling was achievable at no additional diagnostic cost to the FCU/VVS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02371109.National Institute for Health Research (NIHR

Environmental factors modulating the stability and enzymatic activity of the Petrotoga mobilis Esterase (PmEst)

Enzymes isolated from thermophilic organisms found in oil reservoirs can find applications in many fields, including the oleochemical, pharmaceutical, bioenergy, and food/dairy industries. In this study, in silico identification and recombinant production of an esterase from the extremophile bacteria Petrotoga mobilis (designated PmEst) were performed. Then biochemical, bioinformatics and structural characterizations were undertaken using a combination of synchrotron radiation circular dichroism (SRCD) and fluorescence spectroscopies to correlate PmEst stability and hydrolytic activity on different substrates. The enzyme presented a high Michaelis-Menten constant (KM 0.16 mM) and optimum activity at ~55°C for p-nitrophenyl butyrate. The secondary structure of PmEst was preserved at acid pH, but not under alkaline conditions. PmEst was unfolded at high concentrations of urea or guanidine through apparently different mechanisms. The esterase activity of PmEst was preserved in the presence of ethanol or propanol and its melting temperature increased ~8°C in the presence of these organic solvents. PmEst is a mesophilic esterase with substrate preference towards short-to medium-length acyl chains. The SRCD data of PmEst is in agreement with the prediction of an α/β protein, which leads us to assume that it displays a typical fold of esterases from this family. The increased enzyme stability in organic solvents may enable novel applications for its use in synthetic biology. Taken together, our results demonstrate features of the PmEst enzyme that indicate it may be suitable for applications in industrial processes, particularly, when the use of polar organic solvents is required

In vivo axial loading of the mouse tibia

Noninvasive methods to apply controlled, cyclic loads to the living skeleton are used as anabolic procedures to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days

Current Developments in Intraspinal Agents for Cancer and Noncancer Pain

Since the late 1980s, intrathecal (IT) analgesic therapy has improved, and implantable IT drug delivery devices have become increasingly sophisticated. Physicians and patients now have myriad more options for agents and their combination, as well as for refining their delivery. As recently as 2007, The Polyanalgesic Consensus Conference of expert panelists updated its algorithm for drug selection in IT polyanalgesia. We review this algorithm and the emerging therapy included. This article provides an update on newly approved as well as emerging IT agents and the advances in technology for their delivery