bluuebunny/crossref_metadata_2025 huggingface dataset:
Switching from body surface area‐based to fixed dosing for the investigational proteasome inhibitor ixazomib: a population pharmacokinetic analysis
Authors: Gupta Neeraj , Zhao Yuan , Hui Ai‐Min , Esseltine Dixie‐Lee , Venkatakrishnan Karthik
Published: November 2014

Aims

This population pharmacokinetic analysis of the investigational oral proteasome inhibitor ixazomib assessed the feasibility of switching from body surface area (BSA)‐based to fixed dosing, and the impact of baseline covariates on ixazomib pharmacokinetics.

Methods

Data were pooled from 226 adult patients with multiple myeloma, lymphoma or solid tumours in four phase 1 studies, in which ixazomib dosing (oral/intravenous, once/twice weekly) was based on BSA. Population pharmacokinetic modelling was undertaken using nonmem version 7.2.

Results

Ixazomib pharmacokinetics were well described by a three compartment model with first order absorption and linear elimination. Ixazomib was absorbed rapidly (Ka 0.5 h−1), with dose‐ and time‐independent pharmacokinetics. Estimated absolute bioavailability and clearance were 60% and 2 l h−1, respectively. Although a small effect of BSA (range 1.3–2.6 m2) was observed on the peripheral volume of distribution (V4), reducing the corresponding inter‐individual variability by 12.9%, there was no relationship between BSA and ixazomib clearance (the parameter that dictates total systemic exposure following fixed dosing). Consistently, based on simulations (n = 1000), median AUCs (including interquartile range) were similar after BSA‐based (2.23 mg m−2) and fixed (4 mg) oral dosing with no trend in simulated AUC vs. BSA for fixed dosing (P = 0.42). No other covariates, including creatinine clearance (22–213.7 ml min−1) and age (23–86 years), influenced ixazomib pharmacokinetics.

Conclusions

This analysis supports a switch from BSA‐based to fixed dosing, without dose modification for mild/moderate renal impairment or age, in future adult studies of ixazomib, simplifying dosing guidance and clinical development.
Stem cell therapies for systemic sclerosis
Authors: Cipriani Paola , Ruscitti Piero , Giacomelli Roberto
Published: November 2014

The presence of autoimmune diseases, including Systemic Sclerosis (SSc), suggest failure of the normal immune regulatory processes leading to activation and expansion of autoreactive effector immune cells. Recently, stem cell transplantation emerged as a novel rescue therapy for a variety of refractory autoimmune diseases. The therapeutic strategy involves the ablation of the aberrant self‐reactive immune cells by chemotherapy and the regeneration of a new self‐tolerant immune system formed by the transplanted stem cells. In the last few years, thousands of patients worldwide have received haematopoietic stem cell transplantation (HSCT), mostly autologous, as treatment for severe irreversible autoimmune diseases, with promising results. Here we review the results of published small series of SSc patients treated with allogeneic and autologous HSCT, as well as three randomized trials, exploring the safety and efficacy of autologous HSCT in SSc. Although the results are encouraging, nonetheless, the correct application of stem cell transplantation remains an area of active investigation. Results of larger randomized, double blind clinical trials, will certainly improve our knowledge of the appropriate clinical use of stem cell therapy in SSc patients.
The Unique Binding Mode of Laulimalide to Two Tubulin Protofilaments
Authors: Churchill Cassandra D. M. , Klobukowski Mariusz , Tuszynski Jack A.
Published: November 2014

Laulimalide, a cancer chemotherapeutic in preclinical development, has a unique binding site located on two adjacent β‐tubulin units between tubulin protofilaments of a microtubule. Our extended protein model more accurately mimics the microtubule environment, and together with a 135 ns molecular dynamics simulation, identifies a new binding mode for laulimalide, which differs from the modes presented in work using smaller protein models. The new laulimalide–residue interactions that are computationally revealed explain the contacts observed via independent mass shift perturbation experiments. The inclusion of explicit solvent shows that many laulimalide–tubulin interactions are water mediated. The new contacts between the drug and the microtubule structure not only improve our understanding of laulimalide binding but also will be essential for efficient derivatization and optimization of this prospective cancer chemotherapy agent. Observed changes in secondary protein structure implicate the S7–H9 loop (M–loop) and H1′–S2 loop in the mechanism by which laulimalide stabilizes microtubules to exert its cytotoxic effects.
A novel frameshift mutation of epithelial sodium channel β‐subunit leads to Liddle syndrome in an isolated case
Authors: Yang Kun‐Qi , Lu Chao‐Xia , Xiao Yan , Liu Ya‐Xin , Jiang Xiong‐Jing , Zhang Xue , Zhou Xian‐Liang
Published: November 2014

Objective

Liddle syndrome, an autosomal dominant form of monogenic hypertension, is attributed to mutations in the genes encoding β and γ subunits (SCNN1B and SCNN1G) of the epithelial sodium channel (ENaC). The aim of this study was to search for pathogenic mutations of SCNN1B and SCNN1G in an adolescent under the impression of Liddle syndrome and no family history of hypertension.

Design and Patients

We screened the C‐terminus of SCNN1B and SCNN1G in an adolescent with poorly controlled hypertension who was clinically diagnosed as having Liddle syndrome. We also screened for the mutation in his parents, 100 hypertensive patients and 100 controls.

Results

Genetic analysis of SCNN1B revealed a frameshift mutation induced by insertion of an additional cytosine into a string of six located between codons 617 and 618, which is predicted to introduce a new termination codon at position 621 and produce a protein truncated by 20 amino acids. This frameshift mutation was not detected in the patient's parents, the 100 hypertensive patients or the 100 controls, indicating that this is a de novo mutation and not a common genetic polymorphism. There was no mutation of SCNN1G in any of the individuals examined.

Conclusion

Based on direct DNA sequencing, we identified a novel frameshift mutation in the βENaC gene in an isolated case of Liddle syndrome. Confirmation of the diagnosis and effective tailored treatment in the patient were achieved, implying that genetic testing is a useful tool to diagnose Liddle syndrome.
Status of thousand cankers disease on eastern black walnut in the easternUnitedStates at two locations over 3 years
Authors: Griffin G. J.
Published: November 2014

Thousand cankers disease (TCD), a lethal fungal dieback of eastern black walnut (Juglans nigra), caused byGeosmithia morbida, and spread by the walnut twig beetle,Pityophthorus juglandis, was documented in 2009 to be very destructive in the western United States and was identified in the native range ofJ. nigraat Knoxville, Tennessee, in 2010, and in 2011 at Richmond, Virginia. Beginning late 2010, we studied branch dieback levels (per cent live crown) and newTCDsymptom development at these two quarantined locations monthly for 3 years. Of the 106 trees studied (53 at each location), 31 trees had low live crown ratings of 70 to 0% with little change over the 3 years of the study. One per cent of the trees developed new symptoms on a per‐year basis. Thus, a moderate level ofTCD(mean = 76% live crown) was present in these two locations, and most trees were in a quiescent or dormantTCDcondition for 3 years, an important finding not previously reported. We found newTCDsymptoms developed in Richmond in 2011 and 2012 when precipitation from January 1 to the end of August was low (60–64 cm), and not when the precipitation in Richmond was higher (99 cm). In late 2012, in Richmond, soil water potential assays indicated that some black walnut trees were under severe physiological stress (−15 bars). In contrast, in 2013, high precipitation levels (99 and 130 cm) and high soil water potentials (−0.1 to −3 bars) at both locations were associated with extensive new foliage and stem growth and recovery fromTCD. Further research is needed on water relationships in regard toTCDand black walnut health.
sec‐Butyl‐propylacetamide (SPD) and two of its stereoisomers rapidly terminate paraoxon‐induced status epilepticus in rats
Authors: Bar‐Klein Guy , Swissa Evyatar , Kamintsky Lyn , Shekh‐Ahmad Tawfeeq , Saar‐Ashkenazy Rotem , Hubary Yechiel , Shrot Shai , Stetlander Liran , Eisenkraft Arik , Friedman Alon , Bialer Meir
Published: November 2014

Objective

Organophosphates (OPs) are commonly used insecticides for agriculture and domestic purposes, but may also serve as nerve agents. Exposure to OPs result in overstimulation of the cholinergic system and lead to status epilepticus (SE), a life‐threatening condition that is often resistant to treatment. SE is associated with significant neuronal damage, neurocognitive dysfunction, and the development of lifelong epilepsy. Therefore, rapid termination of SE and prevention of brain damage is of high interest. Here we tested the efficacy of sec‐butyl‐propylacetamide (SPD) and two of its individual stereoisomers, (2S,3S)‐SPD and (2R,3R)‐SPD, in discontinuing OP‐induced seizures. SPD is a one carbon homolog of valnoctamide, a central nervous system (CNS)–active constitutional isomer of valproic acid (VPA) corresponding amide valpromide.

Methods

Rats were implanted with epidural telemetric electrodes to allow electrocorticography (ECoG) recording 24 h prior, during and 24 h after poisoning with the OP paraoxon (at a dose equivalent to 1.4 LD50 Median lethal dose). All rats were provided with antidotal treatment of atropine and toxogonin. Epileptic activity was measured using a novel automated system to evaluate the different effects of midazolam, SPD, and its individual stereoisomers in comparison to nontreated controls.

Results

Treatment with SPD or its individual stereoisomer (2S,3S)‐SPD significantly shorten paraoxon‐induced SE and reduced the duration of recorded pathologic activity after SE was terminated. (2S,3S)‐SPD was superior to racemic‐SPD in diminishing delayed pathologic epileptiform activity within the first 8 h after SE.

Significance

These results suggest SPD as an efficient drug for the rapid termination of SE and pathological epileptiform activity following OP poisoning, a strategy to reduce neuronal dysfunction and the risk for lifelong epilepsy.
Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg
Authors: Powell Kim L. , Tang Howard , Ng Caroline , Guillemain Isabelle , Dieuset Gabriel , Dezsi Gabi , Çarçak Nihan , Onat Filiz , Martin Benoît , O'Brien Terence J. , Depaulis Antoine , Jones Nigel C.
Published: November 2014

Objective

Originally derived from a Wistar rat strain, a proportion of which displayed spontaneous absence‐type seizures, Genetic Absence Epilepsy Rats from Strasbourg (GAERS) represent the most widely utilized animal model of genetic generalized epilepsy. Here we compare the seizure, behavioral, and brain morphometric characteristics of four main GAERS colonies that are being actively studied internationally: two from Melbourne (MELB and STRAS‐MELB), one from Grenoble (GREN), and one from Istanbul (ISTAN).

Methods

Electroencephalography (EEG) recordings, behavioral examinations, and structural magnetic resonance imaging (MRI) studies were conducted on GAERS and Non‐Epileptic Control (NEC) rats to assess and compare the following: (1) characteristics of spike‐and‐wave discharges, (2) anxiety‐like and depressive‐like behaviors, and (3) MRI brain morphology of regions of interest.

Results

Seizure characteristics varied between the colonies, with MELB GAERS exhibiting the least severe epilepsy phenotype with respect to seizure frequency, and GREN GAERS exhibiting four times more seizures than MELB. MELB and STRAS‐MELB colonies both displayed consistent anxiety and depressive‐like behaviors relative to NEC. MELB and GREN GAERS showed similar changes in brain morphology, including increased whole brain volume and increased somatosensory cortical width. A previously identified mutation in the Cacna1h gene controlling the CaV3.2 T‐type calcium channel (R1584P) was present in all four GAERS colonies, but absent in all NEC rats.

Significance

This study demonstrates differences in epilepsy severity between GAERS colonies that were derived from the same original colony in Strasbourg. This multi‐institute study highlights the potential impact of environmental conditions and/or genetic drift on the severity of epileptic and behavioral phenotypes in rodent models of epilepsy.
Variable electrobehavioral patterns during focal nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid
Authors: Arcieri Salvatore , Velotti Rosa , Noè Francesco , Carriero Giovanni , Cattalini Alessandro , Galbardi Barbara , Gnatkovsky Vadym , de Curtis Marco
Published: November 2014

Objective

Nonconvulsive status epilepticus (ncSE) is a severe condition that may result in neurologic sequelae and epilepsy resistant to pharmacologic treatment. We analyze here seizure and electroencephalography (EEG) patterns and their correlation to the development of a chronic epileptic condition in a guinea pig model of focal ncSEinduced by intrahippocampal injection of kainic acid (KA).

Methods

Electrobehavioral patterns during ncSEinduced by unilateral injection of 1 μg ofKAin theCA1 region of the hippocampus were characterized by continuous video‐EEGmonitoring in 13 guinea pigs bilaterally implanted with recording electrodes in the hippocampus and neocortex.

Results

Video‐EEGanalysis demonstrates a high variability of seizure type and duration duringKA‐induced ncSE. Seizures showed focal signs correlated with diverse epileptiformEEGdischarge distributions, either diffuse or localized. Nonfocal (bilateral motor) signs during seizures most likely correlated with a diffuseEEGpattern. The evolution into a chronic epileptic condition correlated neither with the severity of seizure pattern nor with the diffusion of theEEGdischarges observed during the ncSE.

Significance

Video‐EEGmonitoring in a guinea pig model of ncSEinduced by unilateral hippocampal injection ofKAdemonstrates a high variability of electrobehavioral patterns. We demonstrate that the seizure severity score during focal ncSEis not a predictor of the evolution into a chronic epileptic condition of mesial temporal lobe epilepsy.
Intra‐articular treatment with triamcinolone compared with triamcinolone with hyaluronate: A randomised open‐label multicentre clinical trial in 80 lame horses
Authors: de Grauw J. C. , Visser‐Meijer M. C. , Lashley F. , Meeus P. , van Weeren P. R.
Published: November 2014

Reasons for performing study

Intra‐articular (IA) injection of corticosteroids with or without hyaluronate (HA) has been used for decades in equine practice for treatment of noninfectious synovitis and osteoarthritis. However, to date, no large‐scale randomised equine field trials have been reported that address the supposed superior clinical efficacy of the combination of corticosteroid +HAcompared withIAinjection of corticosteroid alone.

Objectives

To compare the clinical efficacy ofIAtriamcinolone acetonide (TA, 12 mg) compared withIA TA(12 mg) + high molecular weightHA(20 mg) in horses with clinical joint disease.

Study design

Prospective, randomised, parallel, open label, multicentre clinical trial.

Methods

Eighty client‐owned horses from 13 clinics were included. Lameness and effusion scores were assessed at baseline and 3 weeks afterIAtreatment. A standardised telephone questionnaire was completed between the owner and consulting veterinarian at 3 months. The primary outcome parameter was clinical success rate, defined as ≥2 grades lameness reduction (on a 0–5 scale) at 3 weeks. Chi‐square statistics and binary logistic regression were used to analyse data on an intention‐to‐treat basis for the 3 week outcome.

Results

The success rate ofIA TA3 weeks after treatment was 87.8%, while that ofTA+HAwas 64.1% (P = 0.01). Age >13 years was associated with a reduced success rate for the combination treatment (P = 0.004) at 3 weeks. At 3 months, half the horses in each group had returned to their previous level of performance.

Conclusions

The combination of TA with HA was associated with a lower short‐term clinical success rate and a similar medium‐term outcome compared withIATA, with only half of the horses performing at their previous level of exercise after 3 months regardless of treatment group allocation.
Syringin may exert sleep‐potentiating effects through the NOS/NO pathway
Authors: Cui Yue , Zhang Ying , Liu Gang
Published: November 2014

Sleep is essential for basic survival as well as for optimal physical and cognitive performance in both human beings and animals. To investigate the effect of syringin on sleep of anesthetized mice and the potential mechanisms, 35 male Kunming mice were randomly divided into six experimental groups (n = 5) and one control group (n = 5). Sleep latency and sleep duration, as well as nitric oxide (NO) content and nitric oxide synthase (NOS) activity, were determined after syringin administration. The NO precursor l‐Arginine (l‐Arg) or NOS inhibitor NG‐Nitro‐l‐arginine methyl ester (l‐NAME) was administered alone or in combination with syringin, and time for sleep latency and duration was recorded. After intragastric administration of syringin, sleep latency decreased in a dose‐ and time‐dependent manner, concomitant with increased sleep duration. The optimal sleep performance was obtained when syringin was given at a dose of 80 mg/kg for eight consecutive days. Syringin significantly reduced NO concentration and NOS activity. Administration of l‐Arg prolonged sleep latency and shortened sleep duration, and the effects were fully reversed by syringin coadministration. Administration of L‐NAME induced a significant reduction in sleep latency and a corresponding increase in sleep duration, and coadministration of syringin further enhanced the effects. The finding of our study demonstrated that syringin could exert sleep‐potentiating effects on anesthetized mice in a time‐ and dose‐dependent manner, and these effects may be intimately correlated with the NO/NOS pathway.
The capacity to cope with climate warming declines from temperate to tropical latitudes in two widely distributed Eucalyptus species
Authors: Drake John E. , Aspinwall Michael J. , Pfautsch Sebastian , Rymer Paul D. , Reich Peter B. , Smith Renee A. , Crous Kristine Y. , Tissue David T. , Ghannoum Oula , Tjoelker Mark G.
Published: November 2014

As rapid climate warming creates a mismatch between forest trees and their home environment, the ability of trees to cope with warming depends on their capacity to physiologically adjust to higher temperatures. In widespread species, individual trees in cooler home climates are hypothesized to more successfully acclimate to warming than their counterparts in warmer climates that may approach thermal limits. We tested this prediction with a climate‐shift experiment in widely distributed Eucalyptus tereticornis and E. grandis using provenances originating along a ~2500 km latitudinal transect (15.5–38.0°S) in eastern Australia. We grew 21 provenances in conditions approximating summer temperatures at seed origin and warmed temperatures (+3.5 °C) using a series of climate‐controlled glasshouse bays. The effects of +3.5 °C warming strongly depended on home climate. Cool‐origin provenances responded to warming through an increase in photosynthetic capacity and total leaf area, leading to enhanced growth of 20–60%. Warm‐origin provenances, however, responded to warming through a reduction in photosynthetic capacity and total leaf area, leading to reduced growth of approximately 10%. These results suggest that there is predictable intraspecific variation in the capacity of trees to respond to warming; cool‐origin taxa are likely to benefit from warming, while warm‐origin taxa may be negatively affected.
Effect of Lactobacillus buchneri and Lactobacillus plantarum on the fermentation characteristics and aerobic stability of whipgrass silage in laboratory silos
Authors: Wang Musen , Yang Chunhua , Jia Lujie , Yu Kefei
Published: November 2014

The effect of Lactobacillus buchneri, alone or in combination with Lactobacillus plantarum, on the fermentation characteristics and aerobic stability of whipgrass silage was investigated under laboratory conditions. The inoculants were applied at 2 × 106 colony forming units g−1. Uninoculated silages served as control. After treatment, the chopped materials were ensiled in 1.5‐L anaerobic glass jars. Three jars per treatment were sampled on days 2, 4, 8, 15, 30, 45 and 90. After 90 days of fermentation, the silages were subjected to an aerobic stability test lasting 5 days, in which CO2 production, change in pH and microbial numbers were measured to determine the extent of aerobic deterioration. At the end of the fermentation period 90 days, inoculation with L. buchneri or in combination with L. plantarum significantly resulted in higher levels of acetic acid in the silages than other treatments (P < 0.05), thus the activities of yeasts and molds, especially yeasts, were impaired. The application of L. buchneri, alone or in combination of with L. plantarum, improved the aerobic stability of whipgrass silage as reflected by lower pH, CO2 production and yeast and mold counts during aerobic exposure. Combining L. buchneri with L. plantarum or applying L. plantarum alone improved the fermentation characteristics of whipgrass silage in comparison with the control. The application of L. buchneri alone or in combination with L. plantarum improved the aerobic stability of whipgrass silage under laboratory conditions.
A comparison of fibrinogen measurement using TEG® functional fibrinogen and Clauss in cardiac surgery patients
Authors: Agarwal S. , Johnson R. I. , Shaw M.
Published: November 2014

Introduction

Viscoelastic methods of estimating fibrinogen measure clot formation under platelet inhibition; these methods are gaining in popularity because of their convenience and speed. The aim of this study was to compare the results of the TEG® functional fibrinogen (FF) assay with the Clauss fibrinogen method in a group of patients presenting for cardiac surgery and to assess whether they gave equivalent results.

Methods

As part of a larger study evaluation a transfusion algorithm for use in cardiac surgery, 320 paired samples of TEG® FF and Clauss fibrinogen were compared. These were taken from 160 patients undergoing cardiac surgery at two time points – prior to heparinisation and 10 min after the administration of protamine. The results of the two fibrinogen measurements were also analysed in relation to the platelet count at the time.

Results

There was no significant correlation between the TEG® FLEV and Clauss fibrinogen at baseline (R2 = 0.106) or 10 min postprotamine (R2 = 0.025) The TEG® FF maximal amplitude and the Clauss were also found to have no significant correlation (at baseline R2 = 0.061), at 10 min postprotamine (R2 = 0.260). Bland–Altman analysis showed no significant agreement between the two methods.

Conclusion

The TEG® FF does not produce results equivalent to those of the Clauss fibrinogen regardless of platelet count.
Influence of Spark Plasma Sintering (SPS) Conditions on Transmission of MgAl2O4 Spinel
Authors: Morita Koji , Kim Byung‐Nam , Yoshida Hidehiro , Hiraga Keijiro , Sakka Yoshio
Published: November 2014

The effects of the spark plasma sintering (SPS) parameters, such as heating rate α, temperature T and soak time ts, and impurities on in‐line transmission Tin were examined in MgAl2O4 spinel. The SPS processing at T = 1300°C for ts = 20 min with a low heating rate of α = 10°C/min is a preferable condition for attaining higher Tin. For the higher T or the longer ts, grain coarsening enhanced the coalescence of residual pores and second phase precipitation, resulting to the limited Tin even at the slow α. Although the lower T and longer ts attained fine and dense microstructure simultaneously, the maximum Tin was limited to about 50%. The limited transmission, particularly in the visible range, can be ascribed to the discoloration caused by the carbon contamination. The carbon contamination arose from the preexisting trace CO3 impurities, irrespective of the SPS conditions. For the higher α, which is the primary advantage of the SPS technique, the additional carbon contamination occurred from the paper/die and remained as glassy carbon in the matrix. To attain higher Tin by the SPS technique, the lower α and T, and the shorter ts should be utilized after removing the impurities.
Phase Transformation Behavior of a Pyrochlore‐Type CeO2–ZrO2 Binary Compound
Authors: Morikawa Akira , Yamamura Kae , Suda Akihiko , Tanabe Toshitaka , Nobukawa Takeshi , Chiba Akiya , Takahashi Naoki
Published: November 2014

The phase transformation behavior of the superlattice structure of a CeO2–ZrO2 pyrochlore‐type binary compound (CP) was investigated so as to better understand how to improve the thermal stability of such a system. CP was synthesized through high‐temperature reduction of a conventional CeO2–ZrO2 solid solution with a 1:1 molar ratio of Ce and Zr. High‐resolution transmission electron microscopy and selected‐area electron diffraction clearly revealed that the pyrochlore structure of CP transformed to the standard disordered cubic fluorite or tetragonal zirconia structure after having been subjected to a high‐temperature durability test; moreover, it was determined that this phase transformation moves inward from the crystallite surface. This discovery suggests a new method by which to improve upon this material for practical applications.
A Coated Infiltration Growth Technique for Fabricating Single‐Grain Y–Ba–Cu–O Bulk Superconductor
Authors: Li Guo‐Zheng , Dong Lei , Deng Jian‐Hua , Deng Xiang‐Yun , Yang Wan‐Min
Published: November 2014

A coated infiltration growth technique was proposed to fabricate single‐grain Y?Ba?Cu?O bulk superconductor, in which a liquid source coated Y2BaCuO5 (Y‐211) preform was employed and the liquid source composition was 3BaO + 5CuO. Experimental results indicated that, the sample exhibited a single‐grain morphology on the top surface, and the liquid source coating always existed surrounding the bulk which contributed to the complete growth of the sample. The homogeneous distribution of fine Y‐211 inclusions in microstructure and a satisfactory Jc performance of 5.67 × 104 A/cm2 in self‐field at 77 K have also been observed.
Hawk mimicry in cuckoos and anti‐parasitic aggressive behavior of barn swallows in Denmark and China
Authors: Liang Wei , Møller Anders Pape
Published: November 2014

Hosts of brood parasites defend their nests against parasitism by aggression and subsequently, if parasitized, by rejection of the parasite egg or nestling. Cuckoos have evolved plumage mimicry with convergence towards the phenotype ofAccipiterhawks that are common predators of cuckoo hosts. Here we tested two alternative hypotheses 1) whether barn swallowsHirundo rusticahave evolved less aggressive behavior towards cuckoos in areas of sympatry with more abundantAccipiterhawks; and 2) whether barn swallows have evolved more aggressive anti‐parasite behavior in areas with a single species of cuckoo. We presented dummies of common cuckooCuculus canorus, sparrowhawkAccipiter nisusand Oriental turtledoveStreptopelia orientalis(a benign control) at the nests of barn swallows during breeding, while recording intensity of response and proximity of barn swallows to the dummy. We demonstrated that cuckoos moved away when attacked aggressively and approached more closely by barn swallows showing that barn swallow behavior was efficient at driving away cuckoos. Barn swallows were significantly more aggressive and approached cuckoo and sparrowhawk dummies more closely in Denmark than in China, despite sparrowhawks being relatively more common in Denmark. Responses towards cuckoo dummies differed from responses towards sparrowhawk dummies, showing that barn swallows distinguished between the two different causes of danger. These findings are inconsistent with a less aggressive response towards cuckoo dummies in areas of sympatry with more abundantAccipiterhawks, but consistent with the alternative hypothesis that barn swallows have evolved more aggressive behavior towards cuckoos in areas with a single species of brood parasite, but not in areas with multiple species of parasites, where it is harder for hosts to tell the difference.
Computerized comprehension training for whom and under which conditions is it efficient?
Authors: Potocki A. , Ecalle J. , Magnan A.
Published: November 2014

The purpose of this study was to examine the differential impact of a computer‐based comprehension training programme according to second graders' comprehender profiles. These profiles differed in the children's abilities to process three types of textual information: literal information, text‐connecting inferences and gap‐filling inferences. The results showed that all the profiles improved significantly after the training on the question type that had caused them the greatest amount of difficulty on the pretest. In addition, factors that could a priori predict the effectiveness of the programme were investigated by comparing children who benefited from the instruction (responders) with those who did not benefit (nonresponders). Before instruction, these children differed in their lexical knowledge level and logical reasoning skills, but not in their memory or comprehension‐monitoring abilities. The results support the claim that children with comprehension difficulties form a heterogeneous group and emphasize the need to examine the differential impact of comprehension instruction according to the characteristics of poor comprehenders.
Bacteriophage Mixture Inactivation Kinetics against Escherichia Coli O157:H7 on Hard Surfaces
Authors: Viazis Stelios , Labuza Theodore P. , Diez‐Gonzalez Francisco
Published: November 2014

This study determined the effect of previously described phage cocktail (BEC8) on the inactivation kinetics of a mixture of Escherichia coli (EHEC) O157:H7 strains on food processing surface materials: stainless steel chip (SSC), ceramic tile chip (CTC) and high‐density polyethylene chip (HDPEC). EHEC strains were combined and spot‐inoculated on surfaces in dried or liquid form and BEC8 was applied and incubated at 12, 23, 30 and 37C. EHEC survival was determined on tryptic soy agar. D values ranged from 3.9 min at 37C to 46.7 min at 12C. Z values calculated for SSC, CTC and HDEPC resulted in 26.1, 23.7 and 26.7C for dry cells, respectively, and 23.2, 23.7 and 24.5C for liquid cells, respectively. There was a significant difference in the rate of bacterial inactivation between lower (12 and 23C) and higher temperatures (30 and 37C). These results indicated that BEC8 killed EHEC on hard surfaces rapidly following first‐order kinetics.

Practical Applications

The effect of a previously described phage cocktail (BEC8) on the inactivation kinetics of a mixture of Escherichia coli (EHEC) O157:H7 strains applied on hard food processing surface materials was studied. The results indicated that phages killed EHEC on hard surfaces relatively rapidly following a predictable rate. However, one must consider the long times to achieve a 5‐log reduction when initial cell counts are high. It would take approximately 2–4 h for a 5‐log cfu reduction of liquid cells at 23C. Both the time length and the temperature of application must fit within the industry time scales.
Microbiological, Biochemical and Textural Characteristics of a Tunisian Dry Fermented Poultry Meat Sausage Inoculated With Selected Starter Cultures
Authors: El Adab Sabrine , Essid Ines , Hassouna Mnasser
Published: November 2014

The effect of selected starter cultures (Lactobacillus sakei + Staphylococcus carnosus or L. sakei + S. carnosus + Staphylococcus xylosus) on microbiological, biochemical and textural characteristics of a traditional Tunisian dry fermented poultry meat sausage was investigated. The microbial results showed that lactic acid bacteria and coagulase negative staphylococci represent the two predominant microflora in all stages of ripening. Moreover, the acidifying activity of L. sakei improved the hygienic quality of fermented sausages by reducing the Enterobacteriaceae counts. The moisture content and water activity of control and inoculated sausages decreased in all stages of ripening. Proteolysis and lipolysis were observed both in control and in inoculated sausages. Finally, textural parameters of sausages were not affected by the use of selective starters.

Practical Applications

Poultry meat products provide a suitable environment for proliferation of meat spoilage microorganisms. The increase in resistance of food spoilage microorganisms to current preservatives, the consumer's demand for safe and minimally processed foods and the hazards associated with the use of high doses of chemical preservatives have led to the need for finding safer alternatives in food preservation. Consumers have also become more critical about the use of synthetic additives to preserve food or enhance characteristics such as color and flavor. Hence, there is a growing trend toward minimally processed foods. As a consequence, bacterial antagonism has received considerable attention in food preservation. Nowadays, the need for safe products with standard and desirable technological properties has resulted in the use of starter cultures for the production of the dry fermented sausages to control the fermentation and ripening process, inhibit the growth of undesirable microorganisms and extend the shelf life of the product.
Elevated fecal M2‐pyruvate kinase in children with cystic fibrosis: A clue to the increased risk of intestinal malignancy in adulthood?
Authors: Pang Tamara , Leach Steven T , Katz Tamarah , Jaffe Adam , Day Andrew S , Ooi Chee Y
Published: November 2014

Background and Aim

Adult patients with cystic fibrosis (CF) have an increased risk of gastrointestinal malignancies. We hypothesized that increased intestinal cell turnover beginning in childhood may explain the increased risk of malignancy in early adulthood. Therefore, we aimed to measure fecal M2‐pyruvate kinase (M2‐PK), a biomarker of intestinal cell turnover, in children with CF. To assess whether the increased cell turnover is secondary to intestinal inflammation, the secondary aims were to measure fecal calprotectin and evaluate its association with fecal M2‐PK.

Methods

Fecal samples, for M2‐PK and calprotectin measurements, were prospectively collected from children with CF and healthy controls (HC).

Results

Thirty‐three children with CF (mean [standard deviation] 7.3 [3.8] years old; 29 pancreatic insufficient [PI]) were enrolled and compared with 33 age‐matched HC. Fecal M2‐PK in CF patients (median [interquartile range, IQR]: 4.7 [1.5–9.7]) was greater than HC (1.0 [1.0–1.0] U/mL; P < 0.0001), and higher in PI (median [IQR]: 5.1 [1.8–13.7]) than pancreatic sufficient patients (1.0 [1.0–1.0] U/mL; P = 0.002). Fecal calprotectin was significantly elevated in CF than HC (median [IQR] 61.3 [43.8–143.8] vs 19.5 [19.5–35.1] mg/kg; P < 0.0001). However, there was no correlation between fecal M2‐PK and fecal calprotectin levels among subjects with CF (r = 0.29; P = 0.1).

Conclusion

Increased intestinal cell turnover is present in children with PI CF. The lack of relationship between fecal M2‐PK and calprotectin suggests that contributing factor(s) other than inflammation may be present.
Sleep‐Disordered Breathing and Functional Decline in Older Women
Authors: Spira Adam P. , Stone Katie L. , Rebok George W. , Punjabi Naresh M. , Redline Susan , Ancoli‐Israel Sonia , Yaffe Kristine
Published: November 2014

Objectives

To determine the association between sleep‐disordered breathing (SDB) and decline in instrumental activities of daily living (IADLs) and mobility in older women.

Design

Prospective cohort.

Setting

Minneapolis and Pittsburgh sites of the Study of Osteoporotic Fractures, participants' homes.

Participants

Women with a mean age ± standard deviation of 82.3 ± 3.2 (N = 302).

Measurements

Participants completed a single night of unattended polysomnography and provided data regarding difficulty with IADLs and mobility. They repeated IADL and mobility measures 5.0 ± 0.7 years later.

Results

After adjustment for age, obesity, Mini‐Mental State Examination score, depressive symptoms, history of hypertension and chronic obstructive pulmonary disease, and number of IADL impairments at baseline, women with an apnea‐hypopnea index (AHI) of 15 or greater at baseline had more than twice the odds of an increase in number of IADL difficulties (adjusted odds ratio (aOR) = 2.22, 95% confidence interval (CI) = 1.09–4.53) and of incident IADL difficulty (aOR = 2.43, 95% CI = 1.00–5.92), of women with an AHI less than 5. There was no association between AHI and mobility difficulty. Women in the middle and highest tertiles of oxygen desaturation index had more than double the odds as those in the lowest tertile of an increase in number of IADL difficulties (middle tertile aOR = 2.64, 95% CI = 1.38–5.04, highest tertile aOR = 2.17, 95% CI = 1.13–4.17) and approximately three times the odds of incident IADL difficulty (middle tertile aOR = 2.84, 95% CI = 1.27–6.36, highest tertile aOR = 3.07, 95% CI = 1.31–7.18). Neither sleep fragmentation nor sleep duration was associated with IADL outcomes.

Conclusion

SDB and associated hypoxemia are risk factors for functional decline in older women. Research is needed to determine whether treatment of SDB prevents functional decline.
Surgical management of a traumatic dislocation of the sternum in an English bulldog
Authors: Serra C. I. , Soler C. , Moratalla V. , Sifre V. , Redondo J. I.
Published: November 2014

A nine‐year‐old English bulldog presented with an acute history of dyspnoea, tachycardia and discomfort localising to the ventral thorax following a fall down the stairs that morning. After the dog was stabilised, thoracic radiographs revealed a luxation of the third and fourth sternebrae with dorsal displacement of the caudal segment. The sternum was reduced and stabilised with a contoured 12‐hole 3 · 5‐mm dynamic compression plate applied to the ventral surface of the sternum.

The dog's initial recovery was rapid, cardiorespiratory parameters returning to normal in the first 24 hours. For 2 weeks postoperatively the dog exhibited difficulty in rising from a prone position. After this time there was a full recovery. Clinical examination at 8 months postoperatively did not reveal any abnormalities. Telephone follow‐up was performed at 18 months and no complications or cardiorespiratory compromise were reported. To the authors’ knowledge, this is the first reported case of a traumatic dislocation of the sternum and its management in the dog.
Influence of Naftopidil on Plasma Monoamine Levels and Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia
Authors: KADEKAWA Katsumi , SUGAYA Kimio , MUKOYAMA Hideki , SAKUMOTO Misao , SHIMABUKURO Hiroichi , SHIMABUKURO Syuichi , MATAYOSHI Yukihide , ONAGA Tomohiro , ASHITOMI Katsuhiro , NISHIJIMA Saori
Published: November 2014

Objectives

To clarify the influence of naftopidil, an α1D/A‐adrenergic receptor antagonist, on the autonomic nervous system, we examined the relation between lower urinary tract symptoms (LUTS) and the plasma monoamine levels before and after naftopidil treatment in benign prostatic hyperplasia (BPH) patients.

Methods

A total of 43 patients with BPH were studied. The frequency of urination, international prostate symptom score (IPSS), quality of life (QOL) index, overactive bladder symptom score (OABSS), and plasma monoamine levels (adrenaline, noradrenaline, dopamine, and serotonin) were evaluated before and after naftopidil treatment.

Results

Naftopidil significantly improved urinary frequency in daytime and nighttime, IPSS, QOL index and OABSS in all patients, and decreased the plasma adrenaline level at 8 weeks. When the patients were divided into two groups based on the median adrenaline level (40.5 pg/mL) before treatment, urinary frequency in daytime and/or nighttime, incomplete emptying and poor flow in the IPSS, and the QOL index were significantly improved in the high adrenaline (HA) group, but not in the low adrenaline (LA) group. The pretreatment plasma serotonin level was significantly lower in the HA group than in the LA group, but it increased gradually after the start of treatment until there was no difference between the groups.

Conclusions

The modulation of plasma adrenaline and serotonin levels by naftopidil in patients with increased sympathetic activity contributed to improvement of LUTS associated with BPH, in addition to its antagonistic effects of α1D/A‐adrenergic receptor on the detrusor and prostatic urethral smooth muscle, the urothelium, and the central nervous system.
Krogh‐Cylinder and Infinite‐Domain Models for Washout of an Inert Diffusible Solute from Tissue
Authors: Secomb Timothy W.
Published: November 2014

Objective

Models based on the Krogh‐cylinder concept are developed to analyze the washout from tissue by blood flow of an inert diffusible solute that permeates blood vessel walls. During the late phase of washout, the outflowing solute concentration decays exponentially with time. This washout decay rate is predicted for a range of conditions.

Methods

A single capillary is assumed to lie on the axis of a cylindrical tissue region. In the classic “Krogh‐cylinder” approach, a no‐flux boundary condition is applied on the outside of the cylinder. An alternative “infinite‐domain” approach is proposed that allows for solute exchange across the boundary, but with zero net exchange. Both models are analyzed, using finite‐element and analytical methods.

Results

The washout decay rate depends on blood flow rate, tissue diffusivity and vessel permeability of solute, and assumed boundary conditions. At low blood flow rates, the washout rate can exceed the value for a single well‐mixed compartment. The infinite‐domain approach predicts slower washout decay rates than the Krogh‐cylinder approach.

Conclusions

The infinite‐domain approach overcomes a significant limitation of the Krogh‐cylinder approach, while retaining its simplicity. It provides a basis for developing methods to deduce transport properties of inert solutes from observations of washout decay rates.
Force for ancient and recent life: viral and stem‐loop RNA consortia promote life
Authors: Villarreal Luis P.
Published: November 2014

Lytic viruses were thought to kill the most numerous host (i.e., kill the winner). But persisting viruses/defectives can also protect against viruses, especially in a ubiquitous virosphere. In 1991, Yarmolinsky et al. discovered the addiction modules of P1 phage, in which opposing toxic and protective functions stabilize persistence. Subsequently, I proposed that lytic and persisting cryptic virus also provide addiction modules that promote group identity. In eukaryotes (and the RNA world), a distinct RNA virus–host relationship exists. Retrovirurses/retroposons are major contributors to eukaryotic genomes. Eukaryotic complexity appears to be mostly mediated by regulatory complexity involving noncoding retroposon‐derived RNA. RNA viruses evolve via quasispecies, which contain cooperating, minority, and even opposing RNA types. Quasispecies can also demonstrate group preclusion (e.g., hepatitis C). Stem‐loop RNA domains are found in long terminal repeats (and viral RNA) and mediate viral regulation/identity. Thus, stem‐loop RNAs may be ancestral regulators. I consider the RNA (ribozyme) world scenario from the perspective of addiction modules and cooperating quasispecies (i.e., subfunctional agents that establish group identity). Such an RNA collective resembles a “gang” but requires the simultaneous emergence of endonuclease, ligase, cooperative catalysis, group identity, and history markers (RNA). I call such a collective a gangen (pathway to gang) needed for life to emerge.
Testing the niche variation hypothesis with a measure of body condition
Authors: Lafferty Diana J. R. , Belant Jerrold L. , Phillips Donald L.
Published: November 2014

Individual variation and fitness are cornerstones of evolution by natural selection. The niche variation hypothesis (NVH) posits that when interspecific competition is relaxed, intraspecific competition should drive niche expansion by selection favoring use of novel resources and that among‐individual variation should confer a selective advantage. Population‐level niche expansion could be achieved by all individuals using all available resources, or by each individual using a unique combination of resources, thereby increasing among‐individual dietary niche variation. Although individual variation can lead to species‐level evolutionary and ecological change, observed variation does not ensure a beneficial outcome. We used carbon and nitrogen stable isotope analysis of claw keratin and a Bayesian stable isotope mixing model to estimate the summer (July–September) assimilated diet of individual female black Ursus americanus and brown U. arctos bears. We quantified variation in dietary niche in both populations, and assessed diet relative to percentage body fat. We hypothesized that if the NVH held, percentage body fat would be similar for individuals of the same species across much of the dietary range of observed proportional salmon contributions to individual bear diets. Although we found greater differences in dietary niches between than within species, we observed greater among‐individual dietary variation in the brown bear population. Moreover, we found that within each species individual female bears achieved similar ranges of percentage body fat at various levels of salmon in the diet. Our results provide support for the NVH. Linking individual dietary niches to measures of physiological condition related to fitness can offer new insights into eco‐evolutionary processes related to food resource use.
Effects of rapid thermal annealing on the properties of HfO2/La2O3 nanolaminate films deposited by plasma enhanced atomic layer deposition
Authors: Cao Duo , Cheng Xinhong , Zheng Li , Wang Zhongjian , Xu Dawei , Xia Chao , Shen Lingyan , Wang Qian , Yu Yuehui , Shen DaShen
Published: November 2014

In this work, HfO2/La2O3 nanolaminate films were deposited on Si substrates by plasma enhanced atomic layer deposition with in situ plasma treatment. Different annealing treatments were adopted to change films structure and performance. The upper HfO2 layers in HfO2/La2O3 nanolaminates were easily crystallized after annealing at 800 °C, while all the La2O3 layers kept amorphous. X-ray photoelectron spectroscopy results indicated that LaO(OH) and La(OH)3 peaks became weak, H2O molecules in laminates evaporated during high-temperature annealing. Band diagram analysis showed that valence band offset and band gap widened after 800 °C annealing. Annealing, especially 800 °C annealing, had gentle effect on leakage current, but could obviously change capacitance and permittivity due to tetragonal and cubic phase formed in the HfO2 film.
Large sulfur isotope fractionations associated with Neoarchean microbial sulfate reduction
Authors: Zhelezinskaia Iadviga , Kaufman Alan J. , Farquhar James , Cliff John
Published: November 2014

Dissecting ancient microbial sulfur cycling

Before the rise of oxygen, life on Earth depended on the marine sulfur cycle. The fractionation of different sulfur isotopes provides clues to which biogeochemical cycles were active long ago (see the Perspective by Ueno). Zhelezinskaia
et al.
found negative isotope anomalies in Archean rocks from Brazil and posit that metabolic fluxes from sulfate-reducing microorganisms influenced the global sulfur cycle, including sulfur in the atmosphere. In contrast, Paris
et al.
found positive isotope anomalies in Archean sediments from South Africa, implying that the marine sulfate pool was more disconnected from atmospheric sulfur. As an analog for the Archean ocean, Crowe
et al.
measured sulfur isotope signatures in modern Lake Matano, Indonesia, and suggest that low seawater sulfate concentrations restricted early microbial activity.

Science
, this issue p.
703
, p.
742
, p.
739
; see also p.
735