bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a parent‐designed programme to support tooth brushing of infants and young children
Authors: Huebner CE , Milgrom P
Published: July 2014

Objectives

This study developed and tested an intervention to help parents establish a routine of brushing their young children's teeth twice a day.

Methods

Community‐based participatory research methods were used to engage parents in the design of the intervention to maximize its relevance and acceptability to others. Input was obtained by interviews and focus groups. The resulting intervention was four 90‐min small‐group sessions that provided educational information, direct instruction, practice and peer‐to‐peer problem‐solving. A pre‐ to post‐non‐randomized design was used to evaluate the intervention's effect to increase or maintain parents' twice daily brushing.

Results

Intervention participants were 67 primary caregivers of children under six years of age. Of the 67 initial participants, 50 completed a post‐intervention questionnaire administered 4 to 8 weeks following the intervention. The proportion of parents who reported brushing their young children's teeth twice a day increased significantly from 59 per cent prior to the intervention to 89 per cent post‐intervention (McNemar's X2 = 10.71, P = 0.002). There were concomitant and statistically significant increases over the study period in parents' confidence for brushing twice a day, attitudes about the importance of brushing and their self‐efficacy for tooth brushing. Parents' knowledge of children's oral health, assessed by a 15‐item scale developed for this study (‘Things to Know About Baby Teeth’), also increased significantly.

Conclusions

Twice daily tooth brushing is a low‐cost, effective strategy to reduce the risk of childhood caries. As demonstrated here, community‐based efforts can help parents achieve this important health behaviour.
Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: a promising approach
Authors: Nofal Ahmad , Nofal Eman , Yosef Ayman , Nofal Hager
Published: July 2014

Background

Recalcitrant warts represent a frustrating challenge for both patients and physicians. Although many destructive and immunotherapeutic modalities are available for the treatment of warts, an ideal, universally effective approach has not been explored to date. Recently, intralesional antigen immunotherapy has shown promising efficacy in the treatment of warts. The aim of the study was to evaluate the efficacy and safety of intralesional measles, mumps, and rubella (MMR) vaccine in the treatment of recalcitrant warts.

Methods

The study included 70 adult patients with multiple recalcitrant extragenital warts of different sizes and durations, with or without distant warts. They were directly injected, without a pre‐sensitization skin test, with 0.3 intralesional MMR vaccine into the largest wart at 2‐week intervals until complete clearance or for a maximum of five treatments. Follow‐up was made every month for six months to detect any recurrence.

Results

Sixty‐five patients, 35 men and 30 women, completed the study, and five patients discontinued for various reasons. Complete clearance of the lesions was observed in 41 patients (63%), partial response in 15 patients (23%), and no response in nine patients (14%). Complete response was demonstrated in 74.5% of those presenting with distant warts. Side effects were mild and insignificant in the form of pain during injection, itching, erythema, and edema at the site of injection and flu‐like symptoms. Recurrence was detected in two patients only.

Conclusions

Intralesional immunotherapy by MMR vaccine is a promising, effective, and safe treatment modality for recalcitrant warts.
Facial myiasis and canthariasis associated with systemic lupus panniculitis: a case report
Authors: Smadi Ra'ed , Amr Zuhair S. , Katbeh‐Bader Ahmad , Obidat Nidal , Tawarah Mohammad , Hasan Hazem
Published: July 2014

Background

Infestation of insects can cause myiasis due to dipetran larvae and canthariasis due to coleopteran larval or adult stages.

Objective

To report a case of facial myiasis and canthariasis in a patient known to have panniculitis due to systemic lupus erythematosus and autoimmune hemolytic anemia.

Method

Larval and pupal stages of insects were recovered from the face of a patient, mounted, and identified.

Result

Initially, the pupal stage of the common green bottle fly Lucilia sericata was extracted from the patient's face, treated, and then came back with secondary infestation caused by two species of beetles, the drugstore beetle, Stegobium paniceum, and a beetle of the genus Trogoderma.

Conclusion

This is the first report on facial canthariasis due to larval stages caused by two species of beetles and recovery of pupal stages of the common green bottle fly.
Effects of hospital‐acquired conditions on length of stay for patients with diabetes
Authors: Cromarty J. , Parikh S. , Lim W. K. , Acharya S. , Jackson T. J.
Published: July 2014

Background

Inpatients with diabetes have longer length of stays (LOS). Understanding patterns of in‐hospital complications between patients with diabetes and others may reveal measures to improve patient welfare and minimise LOS.

Aim

This study evaluates the rates and types of hospital‐acquired conditions among patients with and without diabetes and assesses any effects on LOS.

Methods

A total of 47 615 admission episodes from The Northern Hospital over 12 months was reviewed. Episodes were divided into four groups: (i) patients without diabetes; (ii) patients with diabetes without end‐organ sequelae (EOS); (iii) patients with diabetes with EOS; and (iv) a subset of non‐diabetic patients with a Charlson Co‐morbidity score ≥1 (comparison group). The Classification of Hospital Acquired Diagnoses (CHADx) was applied to the groups to compare rates and types of inpatient complications. Linear regression was used to analyse the impact of the number of CHADx on LOS.

Results

Almost 30% of admissions of patients with diabetes and EOS had at least one CHADx, compared with 13% for non‐diabetes patients and 17% for the comparison group. The types of CHADx experienced by diabetes patients with EOS were similar to the comparison group. However, rates were 10 times higher. Linear regression demonstrated diabetes patients with EOS have increased LOS and each CHADx per episode has a larger effect on LOS.

Conclusion

We demonstrate that diabetes patients have consistently higher rates of CHADx and longer LOS than similar patients with complex and chronic conditions. This provides a foundation for future studies to investigate preventative practices for this high‐risk patient population.
Effects of Contingent Reinforcement of Actions on Infants' Object‐Directed Reaching
Authors: Needham Amy , Joh Amy S. , Wiesen Sarah E. , Williams Nicole
Published: July 2014

The role of contingency learning was examined in 3‐month‐old infants' reaching movements. Infants in the experimental group experienced 9 min of active training during which they could move their arms in a reach‐like fashion to pull and move a mobile. Infants in the control group experienced 9 min of passive training during which they watched a mobile move. Prior to (pre‐training) and following the mobile experience (post‐training), infants in both conditions were given an opportunity to interact with a rattle placed within and out of their reach. Compared with infants in the control condition, infants in the experimental condition produced reach‐like movements more frequently during the mobile experience; they also showed a greater increase in reaching attempts from pre‐ to post‐training assessments with the rattle. These findings show that reinforcement of arm extensions and retractions increases the frequency of infants' reaching behaviors. This result suggests that the reinforcement of components of infants' behaviors may contribute to the successful assembly of these behaviors. This process could help keep infants engaged during the lengthy transition from prereaching to independent reaching.
Well‐being, health and fitness of children who use wheelchairs: Feasibility study protocol to develop child‐centred ‘keep‐fit’ exercise interventions
Authors: O'Brien Thomas D. , Noyes Jane , Spencer Llinos Haf , Kubis Hans‐Peter , Edwards Rhiannon T. , Bray Nathan , Whitaker Rhiannon
Published: July 2014

Aim

To undertake the pre‐clinical and modelling phases of the Medical Research Council complex intervention framework to underpin development of child‐centred ‘keep‐fit’, exercise and physical activity interventions for children and young people who use wheelchairs.

Background

Children who use wheelchairs face many barriers to participation in physical activity, which compromises fitness, obesity, well‐being and health. ‘Keep‐fit’ programmes that are child‐centred and engaging are urgently required to enhance participation of disabled children and their families as part of a healthy lifestyle. Nurses will likely be important in promoting and monitoring ‘keep‐fit’ intervention(s) when implemented in the community.

Design

Mixed‐method (including economic analysis) feasibility study to capture child and family preferences and keep‐fit needs and to determine outcome measures for a ‘keep‐fit’ intervention.

Methods

The study comprises three stages. Stage 1 includes a mixed‐method systematic review of effectiveness, cost effectiveness and key stakeholder views and experiences of keep‐fit interventions, followed by qualitative interviews with children, young people and their parents to explore preferences and motivations for physical activity. Stage 2 will identify standardized outcome measures and test their application with children who use wheelchairs to obtain baseline fitness data. Options for an exercise‐based keep‐fit intervention will then be designed based on Stage 1 and 2 findings. In stage 3, we will present intervention options for feedback and further refinement to children and parents/carers in focus groups. (Project funded October 2012).

Discussion

At completion, this study will lead to the design of the intervention and a protocol to test its efficacy.
Pleiotrophin differentially regulates the rewarding and sedative effects of ethanol
Authors: Vicente‐Rodríguez Marta , Pérez‐García Carmen , Ferrer‐Alcón Marcel , Uribarri María , Sánchez‐Alonso María G. , Ramos María P. , Herradón Gonzalo
Published: July 2014

Pleiotrophin (PTN) is a cytokine with important roles in dopaminergic neurons. We found that an acute ethanol (2.0 g/kg, i.p.) administration causes a significant up‐regulation of PTN mRNA and protein levels in the mouse prefrontal cortex, suggesting that endogenous PTN could modulate behavioural responses to ethanol. To test this hypothesis, we studied the behavioural effects of ethanol in PTN knockout (PTN−/−) mice and in mice with cortex‐ and hippocampus‐specific transgenic PTN over‐expression (PTN‐Tg). Ethanol (1.0 and 2.0 g/kg) induced an enhanced conditioned place preference in PTN−/− compared to wild type mice, suggesting that PTN prevents ethanol rewarding effects. Accordingly, the conditioning effects of ethanol were completely abolished in PTN‐Tg mice. The ataxic effects induced by ethanol (2.0 g/kg) were not affected by the genotype. However, the sedative effects of ethanol (3.6 g/kg) tested in a loss of righting reflex paradigm were significantly reduced in PTN‐Tg mice, suggesting that up‐regulation of PTN levels prevents the sedative effects of ethanol. These results indicate that PTN may be a novel genetic factor of importance in alcohol use disorders, and that potentiation of the PTN signalling pathway may be a promising therapeutic strategy in the treatment of these disorders.

image

Ethanol up‐regulates pleiotrophin (PTN), a cytokine important for dopaminergic neurons, in the prefrontal cortex. Ethanol rewarding effects are abolished in mice over‐expressing PTN and enhanced in PTN−/− mice. The results suggest that up‐regulation of PTN in the prefrontal cortex after ethanol administration serves to modulate ethanol effects in the reward system and other ethanol‐induced pharmacological effects including sedation.
Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine, medetomidine, and dexmedetomidine in the horse: a population analysis
Authors: Grimsrud K. N. , Ait‐Oudhia S. , Durbin‐Johnson B. P. , Rocke D. M. , Mama K. R. , Rezende M. L. , Stanley S. D. , Jusko W. J.
Published: July 2014

The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of theα2‐adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses fromin vivodata after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. CompartmentalPKand minimal physiologically basedPK(mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). PopulationPK/PDanalysis was conducted using theMonolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions inHHandHRwere found. The drug concentrations required to obtain inhibition at half‐maximal effect (IC50) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration thanDEX. The developed models demonstrate the use of mechanistic and mPBPK/PDmodels for the analysis of clinically obtainablein vivodata.
Spleen stiffness can non‐invasively assess resolution of portal hypertension after liver transplantation
Authors: Chin Jun Liong , Chan Grace , Ryan John D. , McCormick P. Aiden
Published: July 2014

Background & Aims

Spleen stiffness can be measured by transient elastography. Recent studies have shown that spleen stiffness correlates with hepatic venous pressure gradient and can predict oesophageal varices. Elevated spleen stiffness in cirrhosis has been attributed to splenic tissue hyperplasia and fibrosis, portal hypertension and its consequent hyperdynamic circulation. The aim of this study was to investigate changes to spleen stiffness after orthotopic liver transplantation (OLT) when portal hypertension resolves.

Methods

Twenty‐one patients awaiting OLT were studied prospectively, while 11 post‐transplant patients were recruited as controls. Spleen and liver stiffness were measured with Fibroscan before and at 2–8 weeks after OLT. Criteria applied for spleen stiffness measurement were similar to liver stiffness (≥10 measurements; ≥60% success rate; interquartile range, IQR <30% of median).

Results

Spleen stiffness was significantly higher before OLT compared to post‐transplant patients [75.0 (63.9–75.0) kPa vs. 28.4 (22.0–37.5) kPa; P < 0.0001]. For patients awaiting OLT, 90% (19/21) had oesophageal varices (endoscopically or radiologically). In patients who underwent liver transplantation, spleen stiffness decreased significantly from a median of 75.0 (62.0–75.0) kPa before OLT, to 41.9 (27.0–47.4) kPa at 2 weeks after transplant and 32.9 (29.1–38.0) kPa in the subsequent 4–8 weeks after OLT (P < 0.0001). As expected, liver stiffness measurements reduced from 39.3 (24.9–75.0) kPa to 8.6 (6.8–11.8) kPa in patients receiving OLT (P = 0.0004).

Conclusions

Spleen stiffness can non‐invasively assess changes in portal pressure after liver transplantation and decreases significantly when portal hypertension resolves.
Identifying the core microbial community in the gut of fungus‐growing termites
Authors: Otani Saria , Mikaelyan Aram , Nobre Tânia , Hansen Lars H. , Koné N'Golo A. , Sørensen Søren J. , Aanen Duur K. , Boomsma Jacobus J. , Brune Andreas , Poulsen Michael
Published: July 2014

Gut microbes play a crucial role in decomposing lignocellulose to fuel termite societies, with protists in the lower termites and prokaryotes in the higher termites providing these services. However, a single basal subfamily of the higher termites, the Macrotermitinae, also domesticated a plant biomass‐degrading fungus (Termitomyces), and how this symbiont acquisition has affected the fungus‐growing termite gut microbiota has remained unclear. The objective of our study was to compare the intestinal bacterial communities of five genera (nine species) of fungus‐growing termites to establish whether or not an ancestral core microbiota has been maintained and characterizes extant lineages. Using 454‐pyrosequencing of the 16S rRNA gene, we show that gut communities have representatives of 26 bacterial phyla and are dominated by Firmicutes, Bacteroidetes, Spirochaetes, Proteobacteria and Synergistetes. A set of 42 genus‐level taxa was present in all termite species and accounted for 56–68% of the species‐specific reads. Gut communities of termites from the same genus were more similar than distantly related species, suggesting that phylogenetic ancestry matters, possibly in connection with specific termite genus‐level ecological niches. Finally, we show that gut communities of fungus‐growing termites are similar to cockroaches, both at the bacterial phylum level and in a comparison of the core Macrotermitinae taxa abundances with representative cockroach, lower termite and higher nonfungus‐growing termites. These results suggest that the obligate association with Termitomyces has forced the bacterial gut communities of the fungus‐growing termites towards a relatively uniform composition with higher similarity to their omnivorous relatives than to more closely related termites.
Evaluation of the kinetics and mechanism of action of anti‐integration host factor‐mediated disruption of bacterial biofilms
Authors: Brockson M. Elizabeth , Novotny Laura A. , Mokrzan Elaine M. , Malhotra Sankalp , Jurcisek Joseph A. , Akbar Rabia , Devaraj Aishwarya , Goodman Steven D. , Bakaletz Lauren O.
Published: July 2014

The extracellular polymeric substance produced by many human pathogens during biofilm formation often contains extracellular DNA (eDNA). Strands of bacterial eDNA within the biofilm matrix can occur in a lattice‐like network wherein a member of the DNABII family of DNA‐binding proteins is positioned at the vertex of each crossed strand. To date, treatment of all biofilms tested with antibodies directed against one DNABII protein, Integration Host Factor (IHF), results in significant disruption. Here, using non‐typeable Haemophilus influenzae as a model organism, we report that this effect was rapid, IHF‐specific and mediated by binding of transiently dissociated IHF by anti‐IHF even when physically separated from the biofilm by a nucleopore membrane. Further, biofilm disruption fostered killing of resident bacteria by previously ineffective antibiotics. We propose the mechanism of action to be the sequestration of IHF upon dissociation from the biofilm eDNA, forcing an equilibrium shift and ultimately, collapse of the biofilm. Further, antibodies against a peptide positioned at the DNA‐binding tips of IHF were as effective as antibodies directed against the native protein. As incorporating eDNA and associated DNABII proteins is a common strategy for biofilms formed by multiple human pathogens, this novel therapeutic approach is likely to have broad utility.
Identification of host genes that affect acquisition of an integrative and conjugative element in Bacillus subtilis
Authors: Johnson Christopher M. , Grossman Alan D.
Published: July 2014

Conjugation, a major type of horizontal gene transfer in bacteria, involves transfer of DNA from a donor to a recipient using donor‐encoded conjugation machinery. Using a high‐throughput screen (Tn‐seq), we identified genes in recipients that contribute to acquisition of the integrative and conjugative element ICEBs1 by Bacillus subtilis. We found that null mutations in some genes caused an increase, and others a decrease in conjugation efficiency. Some mutations affected conjugation only when present in recipients. Other mutations affected conjugation when present in donors or recipients. Most of the genes identified are known or predicted to affect the cell envelope. Several encode enzymes involved in phospholipid biosynthesis and one encodes a homologue of penicillin‐binding proteins. Two of the genes identified also affected conjugation of Tn916, indicating that their roles in conjugation may be general. We did not identify any genes in recipients that were essential for ICEBs1 conjugation, indicating that if there are such genes, then these are either essential for cell growth or redundant. Our results indicate that acquisition of ICEBs1, and perhaps other conjugative elements, is robust and not easily avoided by mutation and that several membrane‐related functions affect the efficiency of conjugation.
An Independent Scholar: Lawrence Moonan's Legacy
Authors: Kerr Fergus
Published: July 2014

Lawrence Moonan (1937–2013) pioneered the study of the medieval Scottish philosopher Lawrence of Lindores; he published a major work on the notion of divine omnipotence in early scholasticism; and he kept worrying that in these post-Deistical times many philosophers and theologians have forgotten what it is like to think of God as strictly infinite.
Visual ground pattern modulates flight speed of male Oriental fruit moth Grapholita molesta
Authors: Kuenen Lodewyk P. S. , Gilbert Cole
Published: July 2014

Insects flying in a horizontal pheromone plume must attend to visual cues to ensure that they make upwind progress. Moreover, it is suggested that flying insects will also modulate their flight speed to maintain a constant retinal angular velocity of terrestrial contrast elements. Evidence from flies and honeybees supports such a hypothesis, although tests with male moths and beetles flying in pheromone plumes are not conclusive. These insects typically fly faster at higher elevations above a high‐contrast ground pattern, as predicted by the hypothesis, although the increase in speed is not sufficient to demonstrate quantitatively that they maintain constant visual angular velocity of the ground pattern. To test this hypothesis more rigorously, the flight speed of male oriental fruit moths (OFM) Grapholita molesta Busck (Lepidoptera: Tortricidae) flying in a sex pheromone plume in a laboratory wind tunnel is measured at various heights (5–40 cm) above patterns of different spatial wavelength (1.8–90°) in the direction of flight. The OFM modulate their flight speed three‐fold over different patterns. They fly fastest when there is no pattern in the tunnel or the contrast elements are too narrow to resolve. When the spatial wavelength of the pattern is sufficiently wide to resolve, moths fly at a speed that tends to maintain a visual contrast frequency of 3.5 ± 3.2 Hz rather than a constant angular velocity, which varies from 57 to 611° s−1. In addition, for the first time, it is also demonstrated that the width of a contrast pattern perpendicular to the flight direction modulates flight speed.
How we approach an acquired thrombotic thrombocytopenic purpura patient
Authors: Raval Jay S. , Mazepa Marshall A. , Brecher Mark E. , Park Yara A.
Published: July 2014

Acquired thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, in addition to variable fever and neurologic and renal dysfunction, without an underlying cause. Recent advances in elucidating the pathophysiology of acquired TTP have led to new testing that we have incorporated into our current management of patients with suspected acquired TTP. Despite these developments, much of the treatment for acquired TTP beyond therapeutic plasma exchange (TPE) is based on low‐quality evidence. Our group has a sustained interest in studying and optimizing the use of TPE, along with other concurrent therapies, in acquired TTP patients. Described herein is a summary of how our apheresis consult service approaches requests for TPE in patients with suspected acquired TTP.
Modeling and Analysis of an Offshore Wind Turbine With Fluid Power Transmission for Centralized Electricity Generation
Authors: Laguna Antonio Jarquin
Published: July 2014

This paper presents a mathematical model of an innovative offshore wind turbine with fluid power transmission. The proposed concept is a variable-speed, pitch controlled turbine which differs from conventional technology by using fluid power technology as a medium to transfer the energy from the wind. The final aim is to use several turbines to centralize electricity generation. Unlike conventional variable speed concepts, the proposed turbine comprises a passive-torque control method which allows the turbine to operate at optimal aerodynamic performance for different wind speeds. A numerical model of a single turbine is developed and time-domain simulations are used to analyze the dynamic response of the different operational parameters to a turbulent wind speed input. The results are compared with those of a reference offshore wind turbine with similar characteristics. It is shown that operation below rated wind speed with a passive control is possible for a single turbine with a better dynamic performance than the reference in terms of transmission torque. However, the efficiency of the energy transmission is reduced throughout the operational range. The addition and simulation of more turbines to the hydraulic network is necessary to determine to which extent the benefits of a centralized wind farm compensate for the relatively lower efficiency.
A Replicate Designed Bioequivalence Study To Compare Two Fixed-Dose Combination Products of Artesunate and Amodiaquine in Healthy Chinese Volunteers
Authors: Liu Yun , Hu Chaoying , Liu Gangyi , Jia Jingying , Yu Chen , Zhu Jianmin , Zheng Qingsi , Zhang Kanyin E.
Published: July 2014

Artesun-Plus is a fixed-dose combination antimalarial agent containing artesunate and amodiaquine. The current study was conducted to compare the pharmacokinetic and safety profiles of Artesun-Plus and the WHO-designated comparator product Artesunate Amodiaquine Winthrop. To overcome the high intrasubject variability of artesunate, the study applied a two-sequence and four-period crossover (2 by 4), replicate study design to assess bioequivalence between the two products in 31 healthy male Chinese volunteers under fasting conditions. The results showed that the values of the geometric mean ratios of maximum concentration of drug in plasma (
C
max
) and area under the concentration-time curve from time zero to the last blood sample collection (AUC
0-last
) for the artesunate component in the test and reference products were 95.9% and 93.9%, respectively, and that the corresponding 90% confidence intervals were 84.5% to 108.7% and 87.2% to 101.1%, while the geometric mean ratios for the amodiaquine component in the test and reference products were 95.0% and 100.0%, respectively, and the corresponding 90% confidence intervals were 86.7% to 104.1% and 93.5% to 107.0%. In conclusion, bioequivalence between the two artesunate and amodiaquine fixed-dose combination products was demonstrated for both components. The study also confirmed high intrasubject variability, especially for artesunate: the coefficients of variation (CV) of
C
max
values for the test and reference products were 39.2% and 43.7%, respectively, while those for amodiaquine were 30.6% and 30.2%, respectively.
In Vivo
Activity of Cefquinome against Escherichia coli in the Thighs of Neutropenic Mice
Authors: Shan Qi , Liang Chaoping , Wang Jing , Li Jufeng , Zeng Zhenling
Published: July 2014

Cefquinome is a cephalosporin with broad-spectrum antibacterial activity, including activity against enteric Gram-negative bacilli such as
Escherichia coli
. We utilized a neutropenic mouse model of colibacillosis to examine the pharmacodynamic (PD) characteristics of cefquinome, as measured by organism number in homogenized thigh cultures after 24 h of therapy. Serum drug levels following 4-fold-escalating single doses of cefquinome were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic (PK) properties of cefquinome were linear over a dose range of 10 to 640 mg/kg of body weight. Serum half-lives ranged from 0.29 to 0.32 h. Dose fractionation studies over a 24-h dose range of 2.5 to 320 mg/kg were conducted every 3, 6, 12, or 24 h. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. The free percentage of the dosing interval that the serum levels exceed the MIC (
fT
>MIC
) was the PK-PD index that best correlated with efficacy (
R
2
= 73% for
E. coli
, compared with 13% for the maximum concentration of the free drug in serum [
f
C
max
]/MIC and 45% for the free-drug area under the concentration-time curve from 0 to 24 h [
f
AUC
0-24
]/MIC). Subsequently, we employed a similar dosing strategy by using 4-fold-increasing total cefquinome doses administered every 4 h to treat animals infected with four additional
E. coli
isolates. A sigmoid maximum-effect (
E
max
) model was used to estimate the magnitudes of the %
fT
>MIC
associated with net bacterial stasis, a 1-log
10
CFU reduction from baseline, and a 2-log
10
CFU reduction from baseline; the corresponding values were 28.01% ± 2.27%, 37.23% ± 4.05%, and 51.69% ± 9.72%. The potent bactericidal activity makes cefquinome an attractive option for the treatment of infections caused by
E. coli
.
Sigma S-Dependent Antioxidant Defense Protects Stationary-Phase Escherichia coli against the Bactericidal Antibiotic Gentamicin
Authors: Wang Jing-Hung , Singh Rachna , Benoit Michael , Keyhan Mimi , Sylvester Matthew , Hsieh Michael , Thathireddy Anuradha , Hsieh Yi-Ju , Matin A. C.
Published: July 2014

Stationary-phase bacteria are important in disease. The σ
s
-regulated general stress response helps them become resistant to disinfectants, but the role of σ
s
in bacterial antibiotic resistance has not been elucidated. Loss of σ
s
rendered stationary-phase
Escherichia coli
more sensitive to the bactericidal antibiotic gentamicin (Gm), and proteomic analysis suggested involvement of a weakened antioxidant defense. Use of the p
sfiA
genetic reporter, 3′-(
p
-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm generated more reactive oxygen species (ROS) in the mutant. HPF measurements can be distorted by cell elongation, but Gm did not affect stationary-phase cell dimensions. Coadministration of the antioxidant
N
-acetyl cysteine (NAC) decreased drug lethality particularly in the mutant, as did Gm treatment under anaerobic conditions that prevent ROS formation. Greater oxidative stress, due to insufficient quenching of endogenous ROS and/or respiration-linked electron leakage, therefore contributed to the greater sensitivity of the mutant; infection by a uropathogenic strain in mice showed this to be the case also
in vivo
. Disruption of antioxidant defense by eliminating the quencher proteins, SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and TalA, which provide NADPH for ROS decomposition, also generated greater oxidative stress and killing by Gm. Thus, besides its established mode of action, Gm also kills stationary-phase bacteria by generating oxidative stress, and targeting the antioxidant defense of
E. coli
can enhance its efficacy. Relevant aspects of the current controversy on the role of ROS in killing by bactericidal drugs of exponential-phase bacteria, which represent a different physiological state, are discussed.
Migration of Dendritic Cells Facilitates Systemic Dissemination of Burkholderia pseudomallei
Authors: Williams Natasha L. , Morris Jodie L. , Rush Catherine M. , Ketheesan Natkunam
Published: July 2014

Burkholderia pseudomallei
, the etiological agent for melioidosis, is an important cause of community-acquired sepsis in northern Australia and northeast Thailand. Due to the rapid dissemination of disease in acute melioidosis, we hypothesized that dendritic cells (DC) could act as a vehicle for dissemination of
B. pseudomallei
. Therefore, this study investigated the effect of
B. pseudomallei
infection on DC migration capacity and whether migration of DC enabled transportation of
B. pseudomallei
from the site of infection.
B. pseudomallei
stimulated significantly increased migration of bone marrow-derived DC (BMDC), both
in vitro
and
in vivo
, compared to uninfected BMDC. Furthermore, migration of BMDC enabled significantly increased
in vitro
trafficking of
B. pseudomallei
and
in vivo
dissemination of
B. pseudomallei
to secondary lymphoid organs and lungs of C57BL/6 mice. DC within the footpad infection site of C57BL/6 mice also internalized
B. pseudomallei
and facilitated dissemination. Although DC have previously been shown to kill intracellular
B. pseudomallei
in vitro
, the findings of this study demonstrate that
B. pseudomallei
-infected DC facilitate the systemic spread of this pathogen.
Conserved Oligopeptide Permeases Modulate Sporulation Initiation in Clostridium difficile
Authors: Edwards Adrianne N. , Nawrocki Kathryn L. , McBride Shonna M.
Published: July 2014

The anaerobic gastrointestinal pathogen
Clostridium difficile
must form a metabolically dormant spore to survive in oxygenic environments and be transmitted from host to host. The regulatory factors by which
C. difficile
initiates and controls the early stages of sporulation in
C. difficile
are not highly conserved in other
Clostridium
or
Bacillus
species. Here, we investigated the role of two conserved oligopeptide permeases, Opp and App, in the regulation of sporulation in
C. difficile
. These permeases are known to positively affect sporulation in
Bacillus
species through the import of sporulation-specific quorum-sensing peptides. In contrast to other spore-forming bacteria, we discovered that inactivating these permeases in
C. difficile
resulted in the earlier expression of early sporulation genes and increased sporulation
in vitro
. Furthermore, disruption of
opp
and
app
resulted in greater virulence and increased the amounts of spores recovered from feces in the hamster model of
C. difficile
infection. Our data suggest that Opp and App indirectly inhibit sporulation, likely through the activities of the transcriptional regulator SinR and its inhibitor, SinI. Taken together, these results indicate that the Opp and App transporters serve a different function in controlling sporulation and virulence in
C. difficile
than in
Bacillus subtilis
and suggest that nutrient availability plays a significant role in pathogenesis and sporulation
in vivo
. This study suggests a link between the nutritional status of the environment and sporulation initiation in
C. difficile
.
COMPLEX NUMBERS AS A COMPACT WAY TO REPRESENT SCORES AND THEIR RELIABILITY IN RECOGNITION BY MULTI-BIOMETRIC FUSION
Authors: BARRA SILVIO , DE MARSICO MARIA , NAPPI MICHELE , RICCIO DANIEL
Published: July 2014

Multi-biometric systems are a powerful solution to deal with limitations of single classifiers, therefore improving the final recognition accuracy. The sub-systems composing the final architecture often return supplementary indices of input quality and/or of response reliability, which further qualify each recognition score. These indices can enter different information fusion policies. First, they can be used as weights for the fusion of the corresponding scores, in such a way that less trustworthy responses have a lower influence. Alternatively, they can be used to drive the selection of a subset of systems actually enabled for each fusion operation. The present work discusses their appropriate combination with respective scores, to obtain single values which are easier to handle and compare. It is worth underlining the different nature of quality and reliability measures. The quality estimation of input samples requires a complex analysis of environmental conditions, including capture sensors, besides computations over acquired data. Reliability of a system estimates its ability to return a correct response. As an alternative to combination, some solutions rather estimate the joint distributions of conditional probabilities of the scores from the single subsystems. These solutions require training through a huge number of samples. Furthermore, they assume stable score distributions. Our unified representation of the recognition score and of the corresponding quality/reliability value into a single complex number provides simplification and speed up of fusion of multi-classifier results. It also allows to devise procedures to readily compare the performance of different modules in a multi-biometric system, given that there is no natural ordering of these pairs of values of different nature. Moreover our method achieves performance comparable to top performing schemes, yet does not require a prior estimation of (joint) score distributions. As a matter of fact, though representing an upper bound to the obtainable performance, Likelihood ratio has the limit to require an accurate estimation of score distributions, while our approach relies on the reliability of each single response. This feature is very interesting when the set of relevant subjects may present significant variations over time.
MULTI-SENSOR FUSION FOR VIDEO SEGMENTATION
Authors: SCHEUERMANN BJÖRN , ROSENHAHN BODO
Published: July 2014

Video Segmentation is a fundamental task in computer vision. In many sequences, appearance does not provide enough information to solve the problem. Time-of-Flight cameras provide additional information, namely depth, that can be integrated as an additional feature in a segmentation approach. Typically, the depth information is less sensitive to environment changes. Combined with appearance, this has the potential to be a more robust segmentation method. Motivated by the fact that a simple combination of two information sources might not be the best solution, a novel scheme based on Dempster's theory of evidence is proposed. In contrast to existing methods, the use of Dempster's theory of evidence allows to model inaccuracy and uncertainty. The inaccuracy of the information is influenced by an adaptive weight, that provides a measurement of how reliable a certain information might be. The proposed method is compared with others on a publicly available set of image sequences. The experiments show that the use of the proposed feature fusion improves the segmentation.
ON DYNAMIC FORWARD RATE MODELING AND PRINCIPAL COMPONENT ANALYSIS
Authors: BERMIN HANS-PETER
Published: July 2014

In this paper, we show how to construct dynamic forward rate models in terms of exogenously specified eigenfunctions (or factor loadings). We also show how to link forward rate models with different number of driving Brownian motions to each other in a way consistent with the implied eigenfunctions. Finally, we discuss how to best parameterize the models in the sense of maximizing the number of free parameters for a given set of eigenfunctions.
EVOLUTION OF FIRM SIZE
Authors: GONON LUKAS , ROGERS L. C. G.
Published: July 2014

In this paper, we develop the idea that firm sizes evolve as log Brownian motions dSt = St(σdWt + μdt) where the constants μ, σ are characteristics of the firm, chosen from some distribution, and that the firms are wound up at some random time. At any given time, we see a firm of a given size. What can we say about its characteristics given its size? How would we invest in such a market? What do these assumptions imply about the distribution of sizes? By making simple and well-chosen modeling assumptions, we are able to develop quite concrete forms of the dependence of firm characteristics on size, from which we are able to deduce optimal investment weights as a function of size alone. As in the approach of Fernholz [2002, Stochastic Portfolio Theory. Springer], this avoids the need to estimate growth rates of stocks in order to decide on investment strategy.
Remarks on the Jacobi endomorphisms and the Cartan invariants of ODEs
Authors: Kryński Wojciech
Published: July 2014

We present new formulae for the Cartan invariants of second- and third-order ODEs in terms of the Jacobi endomorphisms.
The affine structure of gravitational theories: Symplectic groups and geometry
Authors: Capozziello Salvatore , Cirilo-Lombardo D. J. , De Laurentis Mariafelicia
Published: July 2014

We give a geometrical description of gravitational theories from the viewpoint of symmetries and affine structure. We show how gravity, considered as a gauge theory, can be consistently achieved by the nonlinear realization of the conformal-affine group in an indirect manner: due to the partial isomorphism between CA(3, 1) and the centrally extended Sp( 8), we perform a nonlinear realization of the centrally extended ( CE )Sp( 8) in its semi-simple version. In particular, starting from the bundle structure of gravity, we derive the conformal-affine Lie algebra and then, by the nonlinear realization, we define the coset field transformations, the Cartan forms and the inverse Higgs constraints. Finally, we discuss the geometrical Lagrangians where all the information on matter fields and their interactions can be contained.
Tectonism and magmatism identified on asteroids
Authors: Buczkowski Debra L. , Wyrick Danielle Y.
Published: July 2014

Linear features generally accepted as tectonic structures have been observed on several asteroids and their presence has implications for the internal structure, strength and evolution of these various bodies. Lineaments observed on the Martian moon Phobos led to the prediction that other cratered small bodies would be similarly lineated. Observations of several small bodies, including Gaspra, Ida, Mathilde, Eros, Itokawa, Steins, Lutetia and Vesta, have identified different physical mechanisms by which linear features can be formed. Analysis shows that asteroid lineaments appear to have different origins, including impact, and that lineament orientations and magnitudes provide important constraints on the interior structure of these bodies. Being a differentiated proto-planet, Vesta is a unique body with which to study the role that internal rheologies and structures play on surface tectonic expression. Vesta presents fractures and grooves similar to the other observed asteroids, but also large-scale graben and trough structures more characteristic of terrestrial planet tectonics. Unlike many terrestrial planets, Vesta's main stressors have, however, been primarily exogenic (e.g. impacts) rather than internally driven. Nevertheless, while the search for volcanic features on Vesta has not been successful, the evaluation of the Brumalia Tholus feature suggests that the geological history of Vesta may have included magmatism.
Convergence of Position Auctions under Myopic Best-Response Dynamics
Authors: Cary Matthew , Das Aparna , Edelman Benjamin , Giotis Ioannis , Heimerl Kurtis , Karlin Anna R. , Kominers Scott Duke , Mathieu Claire , Schwarz Michael
Published: July 2014

We study the dynamics of multiround position auctions, considering both the case of exogenous click-through rates and the case in which click-through rates are determined by an endogenous consumer search process. In both contexts, we demonstrate that dynamic position auctions converge to their associated static, envy-free equilibria. Furthermore, convergence is efficient, and the entry of low-quality advertisers does not slow convergence. Because our approach predominantly relies on assumptions common in the sponsored search literature, our results suggest that dynamic position auctions converge more generally.
Advances in Computed Tomography Imaging Technology
Authors: Ginat Daniel Thomas , Gupta Rajiv
Published: July 2014

Computed tomography (CT) is an essential tool in diagnostic imaging for evaluating many clinical conditions. In recent years, there have been several notable advances in CT technology that already have had or are expected to have a significant clinical impact, including extreme multidetector CT, iterative reconstruction algorithms, dual-energy CT, cone-beam CT, portable CT, and phase-contrast CT. These techniques and their clinical applications are reviewed and illustrated in this article. In addition, emerging technologies that address deficiencies in these modalities are discussed.
Sun Exposure and Melanoma Survival: A GEM Study
Authors: Berwick Marianne , Reiner Anne S. , Paine Susan , Armstrong Bruce K. , Kricker Anne , Goumas Chris , Cust Anne E. , Thomas Nancy E. , Groben Pamela A. , From Lynn , Busam Klaus , Orlow Irene , Marrett Loraine D. , Gallagher Richard P. , Gruber Stephen B. , Anton-Culver Hoda , Rosso Stefano , Zanetti Roberto , Kanetsky Peter A. , Dwyer Terry , Venn Alison , Lee-Taylor Julia , Begg Colin B. ,   for the GEM Study Group
Published: July 2014

Background: We previously reported a significant association between higher UV radiation exposure before diagnosis and greater survival with melanoma in a population-based study in Connecticut. We sought to evaluate the hypothesis that sun exposure before diagnosis was associated with greater survival in a larger, international population-based study with more detailed exposure information.

Methods: We conducted a multicenter, international population-based study in four countries—Australia, Italy, Canada, and the United States—with 3,578 cases of melanoma with an average of 7.4 years of follow-up. Measures of sun exposure included sunburn, intermittent exposure, hours of holiday sun exposure, hours of water-related outdoor activities, ambient ultraviolet B (280–320 nm) dose, histologic solar elastosis, and season of diagnosis.

Results: Results were not strongly supportive of the earlier hypothesis. Having had any sunburn in 1 year within 10 years of diagnosis was inversely associated with survival; solar elastosis—a measure of lifetime cumulative exposure—was not. In addition, none of the intermittent exposure measures—water-related activities and sunny holidays—were associated with melanoma-specific survival. Estimated ambient UVB dose was not associated with survival.

Conclusion: Although there was an apparent protective effect of sunburns within 10 years of diagnosis, there was only weak evidence in this large, international, population-based study of melanoma that sun exposure before diagnosis is associated with greater melanoma-specific survival.

Impact: This study adds to the evidence that sun exposure before melanoma diagnosis has little effect on survival with melanoma. Cancer Epidemiol Biomarkers Prev; 23(10); 2145–52. ©2014 AACR.
The Antarctic holothurian genus Echinopsolus Gutt, 1990 (Dendrochirotida, Cucumariidae): brood pouches, spermatozoa, spermatozeugmata and taxonomic implications
Authors: BOHN JENS MICHAEL , HEß MARTIN
Published: July 2014

An examination of seven Antarctic brooding cucumariid and psolid holothurian species revealed a variety of characters all of them have in common: (1) All are gonochoric. (2) A genital papilla is present on the oral disc (permanent and digitiform in males). (3) Females brood their offspring in five anterior interradial brood pouches that are situated at the transition of body to introvert. (4) Multiple spermatozoa are always bundled to bunch-like spermato-zeugmata. (5) The spermatozoa have a fusiform head and a hollow cylinder-like mid-piece encircling the anterior end of the flagellum. This combination of characters so far is unique, and indicates a close relationship based on common origin. As a consequence, we unite all species sharing this set of synapomorphies in the genus Echinopsolus Gutt, 1990. The herewith included species are: E. acanthocola Gutt, 1990, E. acutus (Massin, 1992) comb. nov., E. charcoti (Vaney, 1906) comb. nov., E. koehleri (Vaney, 1914) comb. nov., E. mollis (Ludwig & Heding, 1935) comb. nov., E. parvipes Massin, 1992 and E. splendidus (Gutt, 1990) comb. nov.. Because the current assignment of Echinopsolus to the family Psolidae can not be retained, the genus is tranferred to the family Cucumariidae, as relationships to taxa within this family are obvious. The peculiar spermatozoa and spermato-zeugmata of all Echinopsolus species are described using light- and electron-microscopical techniques and the results are evaluated and discussed concerning their taxonomy and phylogeny.