bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal and Spatial Quantification of Pain‐ Related Small Fiber Functionality Assessed Using Laser Speckle Contrast Analysis
Authors: Unal‐Cevik Isin
Published: January 2018

Background

This study aimed to establish a practical method for assessing pain symptomatology and develop criteria for quantifying small fiber functions using laser speckle contrast analysis (LASCA).

Methods

Axon flare responses, which reflect small fiber functions, were induced either by histamine or capsaicin applied to the volar surface of the skin of the left forearm. To inhibit small fiber function, local anesthetic cream was applied to the skin of right forearm. The effects on pain symptomatology (severity/timing) and axon flare responses (temporal/spatial characteristics) were measured using LASCA. To highlight the clinical relevance, this method was applied to 3 different types of patients with small fiber dysfunction.

Results

Forty‐four forearms of 22 healthy volunteers were tested. Eutectic mixture local anesthetic cream reduced the severity and duration of pain, abolishing or prolonging the latency to reach 3‐fold higher levels of basal skin microcirculation levels, and decreasing the area and intensity of flare responses. There were positive correlations between pain symptomatology and flare response characteristics in the control forearm. Similar results were confirmed in neuropathic pain patients.

Conclusions

Pain‐related small fiber functions and symptomatology (two‐in‐one method) can be assessed via histamine‐ or capsaicin‐evoked axon flare responses in as little as 15 minutes. The reduction of small fiber functions are characterized by decrease in flare size/intensity at 5 minutes after stimulation and prolongation/abolishment of the latency to reach 3‐fold higher levels of baseline skin microcirculation. LASCA may be applied in the clinic to aid early diagnosis, monitor disease progression, and objectively assess treatment efficacy in patients with neuropathic pain.
Two citrate transporters coordinately regulate citrate secretion from rice bean root tip under aluminum stress
Authors: Liu Mei Ya , Lou He Qiang , Chen Wei Wei , Piñeros Miguel A. , Xu Jia Meng , Fan Wei , Kochian Leon V. , Zheng Shao Jian , Yang Jian Li
Published: January 2018

Aluminum (Al)‐induced organic acid secretion from the root apex is an important Al resistance mechanism. However, it remains unclear how plants fine‐tune root organic acid secretion which can contribute significantly to the loss of fixed carbon from the plant. Here, we demonstrate that Al‐induced citrate secretion from the rice bean root apex is biphasic, consisting of an early phase with low secretion and a later phase of large citrate secretion. We isolated and characterized VuMATE2 as a possible second citrate transporter in rice bean functioning in tandem with VuMATE1, which we previously identified. The time‐dependent kinetics of VuMATE2 expression correlates well with the kinetics of early phase root citrate secretion. Ectopic expression of VuMATE2 in Arabidopsis resulted in increased root citrate secretion and Al resistance. Electrophysiological analysis of Xenopus oocytes expressing VuMATE2 indicated VuMATE2 mediates anion efflux. However, the expression regulation of VuMATE2 differs from VuMATE1. While a protein translation inhibitor suppressed Al‐induced VuMATE1 expression, it releases VuMATE2 expression. Yeast one‐hybrid assays demonstrated that a previously identified transcription factor, VuSTOP1, interacts with the VuMATE2 promoter at a GGGAGG cis‐acting motif. Thus, we demonstrate that plants adapt to Al toxicity by fine‐tuning root citrate secretion with two separate root citrate transport systems.
Unexpected impact of esterification on the antioxidant activity and (photo)stability of a eumelanin from 5,6‐dihydroxyindole‐2‐carboxylic acid
Authors: Micillo Raffaella , Iacomino Mariagrazia , Perfetti Marco , Panzella Lucia , Koike Kenzo , D'Errico Gerardino , d'Ischia Marco , Napolitano Alessandra
Published: January 2018

To inquire into the role of the carboxyl group as determinant of the properties of 5,6‐dihydroxyindole melanins, melanins from aerial oxidation of 5,6‐dihydroxyindole‐2‐carboxylic acid (DHICA) and its DHICA methyl ester (MeDHICA) were comparatively tested for their antioxidant activity. MALDI MS spectrometry analysis of MeDHICA melanin provided evidence for a collection of intact oligomers. EPR analysis showed g‐values almost identical and signal amplitudes (ΔB) comparable to those of DHICA melanin, but spin density was one order of magnitude higher, with a different response to pH changes. Antioxidant assays were performed, and a model of lipid peroxidation was used to compare the protective effects of the melanins. In all cases, MeDHICA melanin performed better than DHICA melanin. This capacity was substantially maintained following exposure to air in aqueous buffer over 1 week or to solar simulator over 3 hr. Different from DHICA melanin, MeDHICA melanin was proved to be fairly soluble in different water‐miscible organic solvents, suggesting its use in dermocosmetic applications.
Development of Cotton Fabrics with Durable UV Protective and Self‐cleaning Property by Deposition of Low TiO2 Levels through Sol–gel Process
Authors: Mishra Anu , Butola Bhupendra Singh
Published: January 2018

In this article, the deposition of TiO2 on cotton fabric using sol–gel technique has been described. Various process routes (pad‐dry‐cure, pad‐dry‐hydrothermal and pad‐dry‐solvothermal) were examined to impart a stable coating of TiO2 on fabric. The role of precursor concentration, process temperature and time of treatment were studied to aim at a wash durable, UV protective and self‐cleaning property in the treated fabric. EDX and ICP‐MS techniques were used to examine the add‐on percentage of TiO2 on cotton fabrics treated via different routes. It has been found that the TiO2 remains largely amorphous and nondurable if it is given a short thermal treatment. To convert the deposited TiO2 to its anatase crystal form, a prolonged hydrothermal treatment for at least 3 h needs to be given. TiO2 deposition levels of less than 0.1% were found to be effective in imparting reasonable degree of UV protection and self‐cleaning property to the cotton fabric. The self‐cleaning ability of the treated fabric against coffee stain was also studied and was found to be related to the process route and the deposition levels of TiO2.
Cutting reduces variation in biomass production of forage crops and allows low‐performers to catch up: A case study of Trifolium pratense L. (red clover)
Authors: Herbert D. B. , Ekschmitt K. , Wissemann V. , Becker A.
Published: January 2018

Re‐growth of fodder plants after grazing and mowing drives the profitability of their cultivation and is therefore an important target trait for plant breeding and agricultural engineering. However, for some fodder plants little is known about their re‐growth dynamics in response to grazing or mowing.

We analysed the native response of plant architecture, leaf morphology and growth performance to experimental cutting in wild Trifolium pratense L. (red clover) plants. A total of 150 potted clover plants were established under controlled field conditions, and half of the plants were cut to 5 cm 3 months after sowing. Each plant was measured every week for 5 months.

The cut and subsequently re‐grown plants carried fewer main branches (−20%), as well as fewer (−13%) and smaller (−32%) leaves than the control plants. However, the cut plants produced an average of 17% more accumulated leaf area (cut + re‐grown leaf area) than the control plants. This discrepancy was explained by variation in the growth strategy of the plants, where the cut plants invariably expressed a second growth phase, while almost half of the untreated plants did not.

Our results suggest that cutting acted as an artificial trigger initiating a second growth phase in the cut plants and thereby contributed to yield increase. Exploiting this mechanism may set new goals for breeding and optimisation of the mowing regime.
Anatomical and phenological implications of the relationship between Schinus polygama (Cav.) (Cabrera) and the galling insect Calophya rubra (Blanchard)
Authors: Guedes L. M. , Aguilera N. , Ferreira B. G. , Becerra J. , Hernández V. , Isaias R. M. S.
Published: January 2018

The success of galling insects could be determined by synchronisation with host plant phenology and climate conditions, ensuring suitable oviposition sites for gall induction and food resources for their survival. The anatomical, histochemical and phenological synchronisation strategies between Calophya rubra (Blanchard) (Hemiptera: Psylloidea) and its host, the evergreen plant Schinus polygama (Cav.) (Cabrera) (Anacardiaceae), in the Mediterranean climate of southern Chile was evaluated and compared to that of the congeneric C. cf. duvauae (Scott) from Brazil and closely related host plant S. engleri in a subtropical climate.

Anatomical, histometric, histochemical and vegetative phenology studies of the stem and galls were conducted from June 2015 to December 2016.

Based on the anatomical, histometric and histochemical analysis, the conical stem gall traits imply gains over the non‐galled stem toward the galling insect survival, but the maintenance of phellem, secretory ducts and pith indicate conservative developmental traits that cannot be manipulated by C. rubra. Our results indicate that the conditions of the Mediterranean climate zone limit C. rubra immature activity during unfavourable periods, probably determining a diapause period and a univoltine life cycle, which are peculiarities of the S. polygama– C. rubra system.

The synchronisation between development and seasonality confers peculiarities to the S. polygama– C. rubra system in the Mediterranean climate zone.
A novel two‐stage seaweed integrated multi‐trophic aquaculture
Authors: Ashkenazi Doron Yehoshua , Israel Alvaro , Abelson Avigdor
Published: January 2018

Marine aquaculture is undeniably a key future direction for the production of food. However, traditional aquaculture involves some significant drawbacks, the major one of which is the surplus discharge of organic matter and dissolved nutrients. To mitigate the environmental impact, integrated multi‐trophic aquaculture (IMTA) systems, which advocate the integration of fed fish with inorganic and organic extractive species, may offer a sustainable solution. This study focuses on an innovative experimental setting, integrating three marine macroalgae species (Ulva rigida, Gracilaria conferta, Hypnea musciformis) serially connected via two‐stage seaweed culture tanks to a finfish culture (the gilthead sea bream; Sparus aurata). The aim was to compare and assess the biofiltration and growth performances of the seaweeds, while altering their order in the two‐stage system. The results indicated U. rigida as the fastest growing species. Ulva rigida also displayed the highest total ammonia nitrogen (TAN) uptake rates and removal efficiency. The design allowed the production of high tissue protein and carbohydrate levels for potential biorefinery uses. Ulva rigida protein content averaged 23%, while that of H. musciformis and G. conferta averaged 25% and 18%, respectively. Hypnea musciformis and G. conferta grown under low nutrient conditions presented a significantly higher total carbohydrate content of nearly 50%, compared to 34% exhibited by U. rigida. In summary, the seaweed pairing in a two‐stage system did not inhibit the performance of each individual species and improved overall production. Consequently, it offers significant advantages for future IMTA systems.
Ross River virus in Australian blood donors: possible implications for blood transfusion safety
Authors: Faddy Helen M. , Tran Thu V. , Hoad Veronica C. , Seed Clive R. , Viennet Elvina , Chan Hiu‐Tat , Harley Robert , Hewlett Elise , Hall Roy A. , Bielefeldt‐Ohmann Helle , Flower Robert L.P. , Prow Natalie A.
Published: January 2018

BACKGROUND

Emerging transfusion‐transmissible pathogens, including arboviruses such as West Nile, Zika, dengue, and Ross River viruses, are potential threats to transfusion safety. The most prevalent arbovirus in humans in Australia is Ross River virus (RRV); however, prevalence varies substantially around the country. Modeling estimated a yearly risk of 8 to 11 potentially RRV‐viremic fresh blood components nationwide. This study aimed to measure the occurrence of RRV viremia among donors who donated at Australian collection centers located in areas with significant RRV transmission during one peak season.

STUDY DESIGN AND METHODS

Plasma samples were collected from donors (n = 7500) who donated at the selected collection centers during one peak season. Viral RNA was extracted from individual samples, and quantitative reverse transcription‐polymerase chain reaction was performed.

RESULTS

Regions with the highest rates of RRV transmission were not areas where donor centers were located. We did not detect RRV RNA among 7500 donations collected at the selected centers, resulting in a zero risk estimate with a one‐sided 95% confidence interval of 0 to 1 in 2019 donations.

CONCLUSION

Our results suggest that the yearly risk of collecting a RRV‐infected blood donation in Australia is low and is at the lower range of previous risk modeling. The majority of Australian donor centers were not in areas known to be at the highest risk for RRV transmission, which was not taken into account in previous models based on notification data. Therefore, we believe that the risk of RRV transfusion transmission in Australia is acceptably low and appropriately managed through existing risk management, including donation restrictions and recall policies.
Measuring the role of the 1959 revolution on Cuba's economic performance
Authors: Jales Hugo , Kang Thomas H. , Stein Guilherme , Garcia Ribeiro Felipe
Published: January 2018

This paper quantitatively measures the impact of the 1959 Cuban revolution on the country'sGDPper capita and exports. We use various policy evaluation methods to obtain a valid counterfactual of Cuba'sGDPper capita after the revolution using other Latin American countries as control candidates. We find evidence that regarding both outcomes, the overall impact of the revolution was negative. We also document a negative effect of the economic embargo imposed by the United States and a sizable, positive effect of Cuba's trade agreement with the Soviet Union.
Experimental Evaluation of Structural Intensity in Two-Dimensional Plate-Type Locally Resonant Elastic Metamaterials
Authors: Al Ba'ba'a H. , Attarzadeh M. A. , Nouh M.
Published: January 2018

Elastic metamaterials utilize locally resonant mechanical elements to onset band gap characteristics that are typically exploited in vibration suppression and isolation applications. The present work employs a comprehensive structural intensity analysis (SIA) to depict the structural power distribution and variations associated with band gap frequency ranges, as well as outside them along both dimensions of a two-dimensional (2D) metamaterial. Following a brief theoretical dispersion analysis, the actual mechanics of a finite metamaterial plate undergoing flexural loading and consisting of a square array of 100 cells is examined experimentally using a fabricated prototype. Scanning laser Doppler vibrometer (SLDV) tests are carried out to experimentally measure the deformations of the metamaterial in response to base excitations within a broad frequency range. In addition to confirming the attenuation and blocked propagation of elastic waves throughout the elastic medium via graphical visualizations of power flow maps, the SIA reveals interesting observations, which give additional insights into energy flow and transmission in elastic metamaterials as a result of the local resonance effects. A drastic reduction in power flow magnitudes to the bulk regions of the plate within a band gap is noticeably met with a large amplification of structural intensity around and in the neighborhood of the excitation source as a compensatory effect. Finally, the theoretical and experimentally measured streamlines of power flow are presented as an alternative tool to predict the structural power patterns and track vortices as well as confined regions of energy concentrations.
Direct and Indirect Noise Generated by Entropic and Compositional Inhomogeneities
Authors: Rolland Erwan O. , De Domenico Francesca , Hochgreb Simone
Published: January 2018

Flow disturbances are generated inside a duct via pulsed injection of helium into a flow of air. This leads to the generation of an acoustic pulse (direct noise), as well as the production of entropic and compositional inhomogeneities, which are convected with the mean flow. As these inhomogeneities are convected through a choked nozzle, they generate indirect noise. The resulting acoustic pressure fluctuations are measured experimentally using pressure transducers upstream of the nozzle. Insight obtained from theoretical models and a time-delay analysis can be used to isolate and extract the contributions of direct and indirect noise in the experimental signal. These results are directly compared to existing one-dimensional (1D) direct and indirect noise models. The experimental measurement of indirect noise is found to be in good agreement with the theoretical models for entropy noise and compositional noise for a compact 1D isentropic nozzle.
Validation of a Numerical Model for Predicting Stalled Flows in a Low-Speed Fan—Part I: Modification of Spalart–Allmaras Turbulence Model
Authors: Lee Kuen-Bae , Wilson Mark , Vahdati Mehdi
Published: January 2018

The original Spalart–Allmaras (SA) model is known to predict premature stall when applied to fan or compressor, which is in line with the observation of other researchers who use the SA model. Therefore, to improve the prediction of the stall boundary, the original SA model was modified by scaling the source term based on the local pressure gradient and the velocity helicity of the flow. Furthermore, a generalized wall function valid for nonzero wall pressure gradient was implemented to improve the accuracy of boundary conditions at the solid wall. This work aims to produce a turbulence model which can be used to model flows near the stall boundary for the transonic fan rotors on relatively coarse grids of around 600k points per passage. Initially, two fan rotors with different design and operating speeds were used to optimize the new parameters in the modified turbulence model. The optimization was based on improving the correlation between measured and numerical radial profiles of the pressure ratio. Thereafter, steady computations were performed for two other fans (by using the same parameters), and the predictions were compared with the experimental data for all the four fan rotors. Numerical results showed a significant improvement over those obtained with the original SA model, when compared against the measured data. Finally, for completeness, it was decided to test the performance of the modified model by comparing the result with measured data for a simple canonical case.
Residual Stress in Additive Manufactured Nickel Alloy 625 Parts
Authors: Bass Lindsey , Milner Justin , Gnäupel-Herold Thomas , Moylan Shawn
Published: January 2018

One of the key barriers to widespread adoption of additive manufacturing (AM) for metal parts is the build-up of residual stresses. In the laser-based powder bed fusion process, a laser selectively fuses metal powder layer by layer, generating significant temperature gradients that cause residual stress within the part. This can lead to parts exceeding tolerances and experiencing severe deformations. In order to develop strategies to reduce the adverse effects of these stresses, the stresses first need to be quantified. Cylindrical Nickel Alloy 625 samples were designed with varied outer diameters, inner diameters, and heights. Neutron diffraction was used to characterize the three-dimensional (3D) stress state throughout the parts. The stress state of the parts was generally comprised of tensile exteriors and compressive interiors. Regardless of part height, only the topmost scan height of each part experienced large reductions in axial and hoop stress. Improved understanding of the residual stress trends will aid in model development and validation leading to techniques to reduce negative effects of the residual stress.
Uncertainty
Analysis for Source Term Evaluation of High Temperature Gas-Cooled Reactor Under Accident
Conditions—Identification of Influencing Factors in Loss-of-Forced Circulation
Accidents
Authors: Honda Yuki , Sato Hiroyuki , Nakagawa Shigeaki , Ohashi Hirofumi
Published: January 2018

One of the key elements in probabilistic risk assessment is the identification and characterization of uncertainties. This paper suggests a procedure to identify influencing factors for uncertainty in source term evaluation, which are important to risk of public dose. We propose the following six steps for the identification in a systematic manner in terms of completeness and transparency of the results using both a logic diagram based on basic equations and expert opinions: (1) identification of uncertainty factors based on engineering knowledge of accident scenario analysis; (2) derivation of factors at the level of physical phenomena and variable parameters by expansion of dynamic equation for the system and scenario to be investigated, (3) extraction of uncertainties in variable parameters; (4) selection of important factors based on sensitivity study results and engineering knowledge; (5) identification of important factors for uncertainty analysis using expert opinions; and (6) integration of selected factors in the aforementioned steps. The proposed approach is tested with a case study for a risk-dominant accident scenario in direct cycle high-temperature gas-cooled reactor (HTGR) plant. We use this approach for evaluating the fuel temperature in terms of reactor dynamics and thermal hydraulic characteristics during a depressurized loss-of-forced circulation (DLOFC) accident with the failure of mitigation systems such as control rod systems (CRS) in a representative HTGR plan. In total, six important factors and 16 influencing factors were successfully identified by the proposed method in the case study. The selected influencing factors can be used as input parameters in uncertainty propagation analysis.
Evaluation of matrix effects on TOF-SIMS data of leu-enkephalin and 1,2-dioleoyl-sn-glycero-3-phosphocholine mixed samples
Authors: Nakano Shusuke , Yamagishi Takayuki , Aoyagi Satoka , Portz André , Dürr Michael , Iwai Hideo , Kawashima Tomoko
Published: January 2018

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is one of the most powerful methods to analyze biomolecules in biological tissues and cells because it provides detailed chemical structure information and chemical images with a high spatial resolution. However, in terms of quantitative analysis, there are issues such as matrix effects that often cause secondary ion intensity changes regardless of the actual concentration in a sample. For instance, the intensity of secondary ions related to peptides is generally suppressed when lipids coexist. Since the evaluation of biomolecules is crucial to understand biological phenomena, it is required to analyze peptides or lipids without matrix effects. Therefore, the mechanism of matrix effects regarding peptides and lipids in TOF-SIMS was investigated in this study. Leu-enkephalin (YGGFL, molecular weight of 555.3 Da) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC, C44H84NO8P, molecular weight 785.6 Da) were employed to prepare model samples. Model samples contain different weight ratios of these two molecules. The intensity of secondary ions related to the peptide or the lipid was compared with control samples containing pure leu-enkephalin or DOPC. As a result, it is indicated that the intensity of DOPC related secondary ions is strongly enhanced by coexisting leu-enkephalin, while the intensity of leu-enkephalin related secondary ions is suppressed by coexisting DOPC especially in a low concentration range of the peptide.
Active control of simply supported cylindrical shells using the weighted sum of spatial gradients control metric
Authors: Aslani Pegah , Sommerfeldt Scott D. , Blotter Jonathan D.
Published: January 2018

It is often desired to reduce sound radiated from cylindrical shells. Active structural acoustic control (ASAC) provides a means of controlling the structural vibration in a manner to efficiently reduce the radiated sound. Previous work has often required a large number of error sensors to reduce the radiated sound power, and the control performance has been sensitive to the location of error sensors. The ultimate objective is to provide global sound power reduction using a minimal number of local error measurements, while also minimizing any dependence on error sensor locations. Recently, a control metric referred to as weighted sum of spatial gradients (WSSG) was developed for ASAC. Specific features associated with WSSG make this method robust under a variety of conditions. In this work, the WSSG control metric is extended to curved structures, specifically a simply supported cylindrical shell. It is shown that global attenuation of the radiated sound power is possible using only one local error measurement. It is shown that the WSSG control metric provides a solution approximating the optimal solution of attenuating the radiated sound power, with minimal dependence on the error sensor location. Numerical and experimental results are presented to demonstrate the effectiveness of the method.
Expression of Genes Involved in Bacteriocin Production and Self-Resistance in Lactobacillus brevis 174A Is Mediated by Two Regulatory Proteins
Authors: Noda Masafumi , Miyauchi Rumi , Danshiitsoodol Narandalai , Matoba Yasuyuki , Kumagai Takanori , Sugiyama Masanori
Published: January 2018

We have previously shown that the lactic acid bacterium
Lactobacillus brevis
174A, isolated from
Citrus iyo
fruit, produces a bacteriocin designated brevicin 174A, which is comprised of two antibacterial polypeptides (designated brevicins 174A-β and 174A-γ). We have also found a gene cluster, composed of eight open reading frames (ORFs), that contains genes for the biosynthesis of brevicin 174A, self-resistance to its own bacteriocin, and two transcriptional regulatory proteins. Some lactic acid bacterial strains have a system to start the production of bacteriocin at an adequate stage of growth. Generally, the system consists of a membrane-bound histidine protein kinase (HPK) that senses a specific environmental stimulus and a corresponding response regulator (RR) that mediates the cellular response. We have previously shown that although the HPK- and RR-encoding genes are not found on the brevicin 174A biosynthetic gene cluster in the 174A strain, two putative regulatory genes, designated
breD
and
breG
, are in the gene cluster. In the present study, we demonstrate that the expression of brevicin 174A production and self-resistance is positively controlled by two transcriptional regulatory proteins, designated BreD and BreG. BreD is expressed together with BreE as the self-resistance determinant of
L. brevis
174A. DNase I footprinting analysis and a promoter assay demonstrated that BreD binds to the
breED
promoter as a positive autoregulator. The present study also demonstrates that BreG, carrying a transmembrane domain, binds to the common promoter of
breB
and
breC
, encoding brevicins 174A-β and 174A-γ, respectively, for positive regulation.

IMPORTANCE
The problem of the appearance of bacteria that are resistant to practical antibiotics and the increasing demand for safe foods have increased interest in replacing conventional antibiotics with bacteriocin produced by the lactic acid bacteria. This antibacterial substance can inhibit the growth of pathogenic bacteria without side effects on the human body. The bacteriocin that is produced by a
Citrus iyo
-derived
Lactobacillus brevis
strain inhibits the growth of pathogenic bacteria such as
Listeria monocytogenes
,
Staphylococcus aureus
, and
Streptococcus mutans
. In general, lactic acid bacterial strains have a system to start the production of bacteriocin at an adequate stage of growth, which is called a quorum-sensing system. The system consists of a membrane-bound histidine protein kinase that senses a specific environmental stimulus and a corresponding response regulator that mediates the cellular response. The present study demonstrates that the expression of the genes encoding bacteriocin biosynthesis and the self-resistance determinant is positively controlled by two transcriptional regulatory proteins.
Temporal and Spatial Distribution of the Acetic Acid Bacterium Communities throughout the Wooden Casks Used for the Fermentation and Maturation of Lambic Beer Underlines Their Functional Role
Authors: De Roos J. , Verce M. , Aerts M. , Vandamme P. , De Vuyst L.
Published: January 2018

Few data have been published on the occurrence and functional role of acetic acid bacteria (AAB) in lambic beer production processes, mainly due to their difficult recovery and possibly unknown role. Therefore, a novel aseptic sampling method, spanning both the spatial and temporal distributions of the AAB and their substrates and metabolites, was combined with a highly selective medium and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) as a high-throughput dereplication method followed by comparative gene sequencing for their isolation and identification, respectively. The AAB (
Acetobacter
species more than
Gluconobacter
species) proliferated during two phases of the lambic beer production process, represented by
Acetobacter orientalis
during a few days in the beginning of the fermentation and
Acetobacter pasteurianus
from 7 weeks until 24 months of maturation. Competitive exclusion tests combined with comparative genomic analysis of all genomes of strains of both species available disclosed possible reasons for this successive dominance. The spatial analysis revealed that significantly higher concentrations of acetic acid (from ethanol) and acetoin (from lactic acid) were produced at the tops of the casks, due to higher AAB counts and a higher metabolic activity of the AAB species at the air/liquid interface during the first 6 months of lambic beer production. In contrast, no differences in AAB species diversity occurred throughout the casks.

IMPORTANCE
Lambic beer is an acidic beer that is the result of a spontaneous fermentation and maturation process. Acidic beers are currently attracting attention worldwide. Part of the acidity of these beers is caused by acetic acid bacteria (AAB). However, due to their difficult recovery, they were never investigated extensively regarding their occurrence, species diversity, and functional role in lambic beer production. In the present study, a framework was developed for their isolation and identification using a novel aseptic sampling method in combination with matrix-assisted laser desorption ionization–time of flight mass spectrometry as a high-throughput dereplication technique followed by accurate molecular identification. The sampling method applied enabled us to take spatial differences into account regarding both enumerations and metabolite production. In this way, it was shown that more AAB were present and more acetic acid was produced at the air/liquid interface during a major part of the lambic beer production process. Also, two different AAB species were encountered, namely,
Acetobacter orientalis
at the beginning and
Acetobacter pasteurianus
in a later stage of the production process. This developed framework could also be applied for other fermentation processes.
Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given Individually, Sequentially, or in Combination
Authors: Torrents de la Peña Alba , de Taeye Steven W. , Sliepen Kwinten , LaBranche Celia C. , Burger Judith A. , Schermer Edith E. , Montefiori David C. , Moore John P. , Klasse Per Johan , Sanders Rogier W.
Published: January 2018

Recombinant soluble HIV-1 envelope glycoprotein (Env) SOSIP trimers are a design platform for inducing broadly neutralizing antibodies (bNAbs) by vaccination. To date, these and alternative designs of native-like trimers, given singly or in pairs, have not induced bNAbs in test animals such as rabbits or macaques. Here, we have evaluated whether trivalent and tetravalent combinations of SOSIP trimers from clades A, B, and C, delivered simultaneously or sequentially, induce better neutralizing antibody responses in rabbits than when given alone. None of the tested formulations led to the induction of bNAbs. We found that BG505 clade A trimers dominated the autologous NAb responses induced by combinations, which probably relates to the presence of immunodominant glycan holes on the BG505 trimer. Furthermore, autologous NAb responses to all individual trimers were reduced when they were delivered in combinations compared with when delivered alone, suggesting that immunogen interference had occurred. Finally, in a sequential regimen, a heterologous clade C trimer cross-boosted NAb responses that were primed by earlier immunizations with clade A and B trimers. Taken together, these findings should allow us to improve the design of immunization regimens based on native-like HIV-1 Env trimers.

IMPORTANCE
A successful HIV-1 vaccine most probably requires a trimeric envelope glycoprotein (Env) component, as Env is the only viral protein on the surface of the virus and therefore the only target for neutralizing antibodies. Native-like Env trimers can induce strain-specific neutralizing antibodies but not yet broadly neutralizing antibodies. To try to broaden the antibody response, we immunized rabbits with soluble native-like Env trimers from three different clades using monovalent, multivalent, and sequential regimens. We found that the neutralizing antibody response against each immunogen was reduced when the immunogens were delivered in combination or sequentially compared to the monovalent regimen. In contrast, when the Env trimers from different clades were delivered sequentially, the neutralizing antibody response could be cross-boosted. Although the combination of native-like Env trimers from different clades did not induce broadly neutralizing antibodies, the results provide clues on how to use native-like trimers in vaccination experiments.
P07 Development of a decision-making tool to aid implementation of the national guideline on extended-interval gentamicin in neonates
Authors: Ruth Hodgins , Deirdre Gilpin , Deirdre Schoen
Published: January 2018

Aim

To implement the dosing and monitoring recommendations of the national gentamicin guideline for neonates1 and the British National Formulary (BNF) for Children.2 To assist the transition with the development of a decision-making flowchart.

Method

A baseline audit (n=30) was conducted in the neonatal unit (NICU) to assess compliance with the national guideline and highlight areas to target for change and improvement. A new local gentamicin guideline and a decision-making flowchart were developed and implemented. Education on the new practices was provided. A post-implementation audit (n=28) was performed to assess compliance and measure changes. The new dosage regimen involved giving a dose of 5 mg/kg every 36 hours to neonates with a postnatal age (PNA) of <7 days, and 5 mg/kg every 24 hours to those with a PNA of ≥7 days. The previous dosing regimen was based on body-weight and postmenstrual age (PMA), and used 24 hourly dosing. Pre-dose (trough) levels were taken before the 2nd dose in both guidelines.

Results

Following the development and implementation of the new guideline and flowchart, compliance with the dosing regimen recommended in the national guideline and in the BNF for Children increased by 83% (10% versus 93%, P<0.001). Compliance with local guidance was reduced by 7% (100% versus 93%, p<0.2). Monitoring of renal function (U and Es/creatinine) increased by 35% (46% versus 81%, p<0.01).

Conclusion

Decision-making tools can improve dosing and monitoring practices and standardise care.3 Introduction of a flowchart led to increased monitoring of renal function in neonates treated with gentamicin. Medication errors post- implementation were due to medical staff following the old dosing regimen, based on PMA, for premature neonates. There were no administration errors resulting from the change from 24 hourly dosing to 36 hourly dosing. Change can be associated with an increased risk of medication errors as staff adjust to new practices. Continued education is required to support staff through the change process.

References

Gentamicin Improvement Project Group. Gentamicin: Guidelines for once daily usage in adult and paediatric settings2016. [Available: www.rcpi.ie].

Paediatric Formulary Committee. BNF for children 2016–20172016. UK: BMJ Group, Pharmaceutical Press and RCPCH Publications Ltd.

Fonzo-Christe C, Guignard B, Zaugg C, et al. Impact of clinical decision support guidelines on therapeutic drug monitoring of gentamicin in newborns. Ther Drug Monit2014;36(5):656–62.
P34 Quality improvement project aimed at reducing gentamicin errors in neonates
Authors: Heather Calvert , Aubrey Makhalira
Published: January 2018

Aim

A level 3 tertiary neonatal unit with a capacity of 40 cots providing intensive care, high dependency care, special care & transitional care services, had 18 gentamicin errors reported between January and June 2017, with 84% errors occurring at prescribing and 16% errors in administration. The majority of errors (67%) were due to the complexity of calculating a 36-hourly time interval between doses. A quality improvement project was undertaken with the aim of reducing the number of gentamicin errors on the unit over a 3 month period.

Method

An overview of all gentamicin errors were presented to the multidisciplinary team (MDT) with a view of gathering ideas for improvement to ensure a team based approach. An action plan was put in place in line with National Patient Safety Agency (NPSA) recommendations1 and initiated in July 2017 based on a plan-do-study-act (PDSA) model.

Results

The PDSA cycles included:

a simplified and standardised dosing interval for dosing of gentamicin after the first dose.

an updated local monograph with dosing intervals and example prescription.

posters displayed in prescribing areas to promote safe and focused prescribing.

a feedback session to the full MDT team regarding improvements made and further feedback.

ensure compliance with policy by promoting updated guideline & on going error monitoring.

consideration of alternative lower risk antibiotic in low risk babies.

incorporation of gentamicin prescribing exercise as part of the new doctor induction. The following interventions will be evaluated in 3 months using Datix reported errors before and after implementation. Sequential PDSA cycles will then be conducted for learning and improvement.

Conclusion

A team based approach, using open communication with regular feedback and review is essential in order to improve the quality of prescribing and gain engagement from medical and non-medical prescribing colleagues. Further audit will be undertaken on monthly basis to evaluate the implementation of improvement measures.
P42 The impact of a change to hospital guidelines on prescribing practices of nebulised 3% w/v ‘hypertonic’ saline
Authors: Diarmaid Semple , Paul McNally , Anne Fitzpatrick , Kenny Adeyemi , Niamh McGrory , Michael Fitzpatrick
Published: January 2018

Aims

Recent conclusive evidence has suggested that, contrary to previous limited evidence, there is no benefit to the use of 3% hypertonic saline (3% HS) in the treatment of bronchiolitis in infants.1,2 This led to a change in the clinical guideline during the 2015/2016 bronchiolitis season. We hypothesised that the use of hypertonic saline was preventing the use of other un-necessary treatments and that inappropriate prescribing would increase following the advice not to give hypertonic saline.

The primary aim of the study was to determine if the removal of 3% hypertonic saline from the institutional clinical guideline would result in reduced prescribing patterns. A secondary aim was to evaluate the overall prescribing compliance with the guideline including in the prescribing of antibiotics and bronchodilators, and identify if the change in the clinical guideline impacted the prescribing of other agents in children admitted with a diagnosis of bronchiolitis.

Methods

Data on medical treatments and hospital outcomes were prospectively collected on all infants in the 2015/2016 season both before and after the change in guideline. Details of all medicines prescribed on the patients Medication Record particularly bronchodilators, antimicrobials and inhaled agents were collected. Patient demographics were collected from medical notes. Results were analysed using chi square and Mann Whitney in Excel and Stata.

Results

128 children (86 before, 42 after the change in guideline) were recruited to the study. Baseline demographics were similar except for a higher proportion of children with RSV in the pre-group. Overall guideline compliance was achieved by 2 infants pre, and 3 infants post guideline change (4%). The use of hypertonic saline decreased significantly after the change in guideline but did not cease (90% pre, 71% post p<0.01). Bronchodilators were used in one in 4 infants and antibiotics in one in 3 infants, and there was no significant difference in these rates before or after the change in guidelines.

Conclusion

The change to the guideline reduced the use of 3%HS, however overall guideline compliance in children with bronchiolitis is poor. Hypertonic saline use decreased when the guideline changed but a significant portion of children before and after the guideline change received medications not indicated in the treatment of bronchiolitis, including bronchodilators and antibiotics. It appears that it remains difficult to ‘do nothing’ for bronchiolitis. Poor clinical practice remains and education of clinical staff is necessary in this regard.

References

Guidance: Bronchiolitis in children: diagnosis and management, NICE (NG9) Published date: June 2015.

Silver AH, Esteban-Cruciani N, Azzarone G, et al. 3% hypertonic saline versus normal saline in inpatient bronchiolitis: A randomised controlled trial. Paediatrics2015;136:1036–1043.
P8 Chemotherapy standardisation in paediatric oncology: the our lady’s children’s hospital (olch) dublin experience
Authors: Owens Cormac , Funston Lesley-Ann , Keane Sinead , Clinton Frieda , Lee Mairead
Published: January 2018

Background/objectives

Several centres (Children’s Hospital Philadelphia, Sick Kids Toronto) and organisations (COG) have developed chemotherapy standardisation programmes to reduce risk, increase efficiency and decrease cost associated with the presciption, preparation and administration of chemotherapy in paediatric patients.

Most European paediatric chemotherapy protocols use different doses, infusion times, hydration protocols and supportive medicine doses for the same drugs. There is huge variety in how individual patients receive the same drugs. This introduces significant, unnecessary, potential risks and complexity.

By 2016 our aim is that all children at our institution should have chemotherapy prescribed, prepared and administered according to a standard institutional protocol.

Design/methods

We set up a multi-disciplinary chemotherapy standardisation group within our department. The project was developed in association with a hospital quality initiative. We reviewed all treatment protocols in use at the current time at OLCH and assessed the variety in chemotherapy administration. We performed staff and parental questionnaires regarding their perceptions of the variety in administration, supportive medicines and discharge times.

We held a meeting of all senior departmental management to review and critique the project and multiple staff education sessions to implement the recommended changes.

Results

There is huge variation in how European protocols mandate that chemotherapy be administered, particularly in protocols using doxorubicin, cisplatin, ifosfamide and cyclophosphamide.

We have developed a standard, institutional document which determines how chemotherapy and supportive medicines are administered, limiting variation and risk, increasing staff efficiency and decreasing lengths of hospital admissions.

Conclusion

There is unnecessary variation in the way chemotherapy is administered to paediatric patients in Europe. Doses should not be changed, but length of chemotherapy infusion and associated hydration/supportive medicines are extremely varied and there is little evidence to say this is beneficial in terms of patient outcomes. Chemotherapy protocols can be standardised, limiting variation, reducing potential risk and increasing staff and ward efficiencies.
3 Pharmaco-stability of plasma-lyte 148 and plasma-lyte 148+5% glucose with commonly used therapeutic agents
Authors: Wignell Andrew
Published: January 2018

Aims

Plasma-Lyte 148 is a balanced, crystalloid intravenous fluid which is both calcium-free and isotonic. It has been demonstrated to reduce the risk of hyperchloraemic metabolic acidosis and iatrogenic hyponatraemia seen with use of normal saline and hypotonic solutions respectively. Investigating the compatibility of Plasma-Lyte 148 and Plasma-Lyte 148+5% gucose with morphine, midazolam, fentanyl, ketamine, clonidine, aminophylline, salbutamol and furosemide will provide vital data to facilitate the introduction of these fluids into routine paediatric practice.

Method

Chemical stability was assessed by high performance liquid chromatography (HPLC) using the ‘Hewlett Packard (Agilent) 1100’ HPLC system. A gradient method with 20 mM ammonium carbonate (A) and acetonitrile (B) mobile phases and an ‘ACE Excel 3 SuperC18’ column was used. The flow rate was set to 0.03 ml/min, temperature to 40°C and injection volume for all drug admixtures to 5 µL apart from ketamine (4 µL) and furosemide (1 µL). Physical stability was assessed by observation of precipitate formation or colour change. Six repeats of each IV fluid and drug mix were assayed at three time points: 0, 2 and 24 hours. pH changes were measured using Fisherbrand Hydrus 300. Normal saline and 5% glucose were used as controls for all experiments.

Results

No precipitate formed in any of the samples. Chemical stability was defined as <5% concentration change. All examined therapeutic agents were stable at 2 and 24 hours relative to control solutions. Relative to starting concentration, all drugs except midazolam were stable to ±3%. Midazolam showed similar variation in concentration with all four fluids. All combinations remained in a safe peripheral administration pH range of 5–9. Plasma-Lyte 148 admixtures were found have a pH closest to that of the blood.

Conclusion

Compared to standard diluents, the tested therapeutic agents are chemically and physically stable for 24 hours at the concentrations measured, and are all stable at commonly encountered Y site concentrations, when diluted with Plasma-Lyte 148 or Plasma-Lyte 148+5% glucose. All are pH stable and all are suitable for peripheral administration.
BET 1: Is routine irrigation of a cutaneous abscess necessary?
Authors: Badour Joshua , Singh Matt , Jones Jeffrey
Published: January 2018

A short cut review was carried out to establish whether the addition of irrigation of the abscess cavity improved outcomes after incision and drainage of a cutaneous abscess. One paper presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this paper are tabulated. It is concluded that in adult patients with cutaneous abscesses routine irrigation during incision and drainage does not improve clinical outcomes.