bluuebunny/crossref_metadata_2025 huggingface dataset:
Wet Partial Oxidation of JP8 in a Well-Insulated Reactor
Authors: Scenna Richard , Gupta Ashwani K.
Published: November 2016

This work investigates wet and dry non-catalytic partial oxidation of JP8 under distributed reaction regime condition. Previous works have demonstrated the potential of the distributed reaction regime to increase hydrogen and carbon monoxide production over conventional non-catalytic reforming and suppress soot formation inside the reactor. Jet propellant 8 (JP8) has a high sulfur content (up to 3000ppm) and a tendency to form coke, making it an ideal candidate for this non-catalytic approach. Experimental results are reported with the reactor operated at fixed oxygen to carbon ratio of 1.08 and steam to carbon ratios varied from 0.0 to 0.23. Numerical simulations were used to determine flame regime and extent of distribution.

Steam provided favorable effects even with trace amounts (S/C=0.01), but more pronounced effects were observed at steam to carbon ratio of 0.17. Syngas composed of 22.5–24.6% hydrogen and 20.1–23.3% carbon monoxide was evolved. Of the hydrocarbons detected, only methane was seen in finite amounts (0.17–0.29%). The increase in performance in terms of reforming efficiency and conversion exceeded what can be ascribed to steam reforming reactions alone. Additional enhancement is attributed to distributed reaction in the reactor. Reforming efficiency of approximately 68–80% is comparable to that from catalytic reforming. Low steam to carbon ratio offers higher sustainability in mobile power systems at reduced costs from direct use of water recovered from fuel cells.
Assessment the Safety of Alternative Aviation Fuels in Aero-Engine
Authors: Liu Ziyu , Yang Xiaoyi , Ding Shuiting
Published: November 2016

There are three challenges existing in the current certification process, which results in three challenges including high cost in fuel refinement, fuel-cost in certification testing, lack available testing condition and the acceptance criteria. If alternative fuel is considered as one of the engine replacement parts, and then the certification of alternative fuels can be achieved through compliance verification. This compliance verification method contain two logical relationships: the mapping from fuel to engine, the gap from petroleum-based aviation turbine fuel to drop-in fuel. For similar analogy to carry out parameterization, the system safety assessment reaches a series of critical parameters related to the engine safety and engine performance which provide the boundaries on the variation of critical parameters. This method is achieved by extracting safety criteria from the “history experience” of petroleum-based aviation turbine fuel in aero-engine and to predict the safety of alternative aviation fuels in aero-engine by “similar analogy”.
Harvesting Natural Salinity Gradient Energy for Hydrogen Production Through Reverse Electrodialysis (RED) Power Generation
Authors: Nazemi Mohammadreza , Zhang Jiankai , Hatzell Marta
Published: November 2016

There is an enormous potential for energy generation from the mixing of sea and river water at global estuaries. If technologies are developed which are capable of converting this energy into a usable form (electricity or fuels), salinity gradient energy may be able to dramatically increase the worlds supply of renewable energy. Here we present a novel approach to convert this source of energy directly into hydrogen and electricity using Reverse Electrodialysis (RED). RED relies on converting ionic current to electric current using multiple membranes and redox based electrodes. A thermodynamic model for RED is created to evaluate the electricity and hydrogen which can be extracted from natural mixing processes. With equal volumes of HC and LC solutions (0.001m3), the maximum energy extracted is found to occur with 5 number of membrane pairs. At this operating point, 0.4 kWh/m3 can be extracted as electrical energy and 0.95 kWh/m3 of energy is extracted as hydrogen energy. The electrical energy conversion efficiency approaches 15%, whereas the hydrogen energy efficiency is 35%. Overall, the maximum system conversion of Gibbs free energy to electrical and hydrogen energy approaches 50%. The results show that as the number of membrane pairs increases from 5 to 20, the hydrogen power density decreases from 13.2 W/m2 to 3.7 W/m2. Likewise, the power density from electrical energy decreases from 1 W/m2 to 0.3 W/m2. This is because of increase in the total membrane area as increasing the number of membrane pairs. The stack voltage increased from 1.5V to 6V as the number of membrane pairs is increased from 5 to 20. This corresponds to an increase in internal resistance from 600 Ω.cm2 to 2400 Ω.cm2. Long term trade-off between improving the system voltage, while decreasing the system resistance will be crucial for improved long term RED performance. Furthermore, optimum operation of RED, depends on proper selection of external resistance. A small external resistance will increase hydrogen energy and decrease electrical energy, particularly using a small number of membrane pairs. With the fixed small external resistance, as increasing the number of membrane pairs, the difference between internal and external resistance increases. Therefore, the load potential and current density do not increase considerably. For the cases analyzed with 8.29 Ω.cm2 external resistance, the maximum current density increases from 11.1 mA/cm2 to 12.4 mA/cm2 as the number of membrane pairs increases from 5 to 20. Likewise, the load potential rises from 92 mV to 102 mV.
Numerical Study on Layout of Refractory Belt and Fouling Deposition in Tangentially Fired Boiler
Authors: Zha Qiongliang , Chen Kai , Zhang Jianwen , Li Jiangtao , Wang Chang’an , Che Defu
Published: November 2016

The refractory belt installed in primary combustion zone provides simplest and most effective solution to suppress ignition delay and enhance combustion stability for low volatile anthracite and lean coal. The fouling deposition generally formed on radiative refractory lined wall of the boiler due to a high surface temperature. The growth of deposition thickness is mainly dependent on the parcile impact on the surface of water wall. A particle capture submodel was used to determine whether a particle was captured to form deposition or not when it reached the furnace wall, and the particle capture criterion was based on the particle’s viscosity and the temperature of the furnace wall. A reduced fouling deposition model was implemented in a three dimensional simulation of a tangentially fired boiler. The numerical investigation was conducted to assess the performance of different layouts of refractory belt. Furnace temperature, surface temperature of refractory belt, and deposition distributions on the furnace wall should be taken into account when layouts of refractory belt are optimized. Based on this, three layouts of refractory belt were proposed for tangentially fired boilers. A numerical investigation was conducted to assess the performance of different layouts of refractory belt and the results showed that the temperature in furnace was increased, and the ignition and combustion processes were stabilized when refractory belts were installed. The reasonable arrangement of refractory belt could reduce the possibility of fouling deposition in furnace.
Measurements of Hydrogen Enriched Combustion of Jet Fuel in Open Flame
Authors: Seibert Michael , Nieh Sen
Published: November 2016

Jet fuel is a common logistics fuel, even for small, mobile systems. At low power output (<2 kWe), technologies such as Stirling engines, thermo electric and thermo-photovoltaic generators have the potential to compete with diesel engines, but require reliable jet fuel combustion. Hydrogen enrichment is presented as a control parameter to improve jet fuel combustion.

Research in fuel reforming gives an opportunity for hydrogen production at the point of use. Hydrogen enriched combustion of jet fuel seeks to take advantage of the energy density of jet fuel and the combustibility of hydrogen.

Experiments were conducted with atomized jet fuel in a 5 kWth open flame. Jet fuel is sprayed through an air atomizing nozzle. Hydrogen was added to either the atomizing air or to a concentric tube supplying the main combustion air. During hydrogen enrichment, jet fuel flow rate was reduced to maintain constant fuel energy input. Temperature is measured vertically and laterally through the flame. Gaseous emissions are measured above the visible flame.

In these experiments, hydrogen represented up to 26% of the fuel energy contribution. Substantial changes to the combustion profile occur with small amounts of hydrogen enrichment. The advantages it provides represent opportunities for reduced size, improved operational reliability and control and reduced pollutant emissions.
Revisiting Parabolic Trough Concentrators for Industrial Process Heat in the United States
Authors: Turchi Craig S. , Kurup Parthiv , Zhu Guangdong
Published: November 2016

After significant interest in the 1970s, but relatively few deployments, the use of concentrating solar collectors for thermal applications, including enhanced oil recovery, desalination, and industrial process heat (IPH), is again increasing in global interest. In particular, recent advances in collector design and manufacturing have led to reduced cost per square meter of aperture area. In this study, analysis of a modern parabolic trough that is suited for use in small solar IPH (SIPH) applications predicts that the installed solar field cost can be as low as $170/m2. A slightly higher cost of $200/m2 is estimated for facilities typical of a SIPH plant size. Full project costs will include additional costs for contingency, piping and heat exchanger interface, and project indirect costs.

The cost for solar-generated heat by SIPH is quantified by defining the levelized cost of heat (LCOH). California offers a favorable environment for SIPH given its good insolation, gas prices typically higher than the national average, and policies promoting solar-thermal deployment. Given historically low gas prices, competing with natural gas remains the primary challenge to deployment. However, this study finds that the solar LCOH for many regions in California is lower than the LCOH from natural gas, using a representative installed solar hardware price and the average price for industrial natural gas in California.

Lastly, modification are in progress to the parabolic trough model within NREL’s System Advisor Model (SAM) to allow users to more easily predict performance for these steam-generation applications.
Stem-piped light activates phytochrome B to trigger light responses in
Arabidopsis thaliana
roots
Authors: Lee Hyo-Jun , Ha Jun-Ho , Kim Sang-Gyu , Choi Han-Kyu , Kim Zee Hwan , Han Yun-Jeong , Kim Jeong-Il , Oh Youngjoo , Fragoso Variluska , Shin Kwangsoo , Hyeon Taeghwan , Choi Hong-Gu , Oh Kyung-Hwan , Baldwin Ian T. , Park Chung-Mo
Published: November 2016

Light conducted through plant tissues activates a photoreceptor in the roots of
Arabidopsis thaliana
.
Inducing transcription from multiple directions
Authors: Mushegian Alexandra A.
Published: November 2016

A kinase phosphorylates both a transcription factor and a histone to activate inflammation-related gene expression.
Selection of Resistance to Clarithromycin in Mycobacterium abscessus Subspecies
Authors: Mougari Faiza , Bouziane Feriel , Crockett Flora , Nessar Rachid , Chau Françoise , Veziris Nicolas , Sapriel Guillaume , Raskine Laurent , Cambau Emmanuelle
Published: November 2016

Mycobacterium abscessus
is an emerging pathogen against which clarithromycin is the main drug used. Clinical failures are commonly observed and were first attributed to acquired mutations in
rrl
encoding 23S rRNA but were then attributed to the intrinsic production of the
erm
(41) 23S RNA methylase. Since strains of
M. abscessus
were recently distributed into subspecies and
erm
(41) sequevars, we investigated acquired clarithromycin resistance mechanisms in mutants selected
in vitro
from four representative strains. Mutants were sequenced for
rrl
,
erm
(41),
whiB
,
rpIV
, and
rplD
and studied for seven antibiotic MICs. For mutants obtained from strain
M. abscessus
subsp.
abscessus
erm
(41) T28 sequevar and strain
M. abscessus
subsp.
bolletii
, which are both known to produce effective methylase,
rrl
was mutated in only 19% (4/21) and 32.5% (13/40) of mutants, respectively, at position 2058 (A2058C, A2058G) or position 2059 (A2059C, A2059G). No mutations were observed in any of the other genes studied, and resistance to other antibiotics (amikacin, cefoxitin, imipenem, tigecycline, linezolid, and ciprofloxacin) was mainly unchanged. For
M. abscessus
subsp.
abscessus
erm
(41) C28 sequevar and
M. abscessus
subsp.
massiliense
, not producing effective methylase, 100% (26/26) and 97.5% (39/40) of mutants had
rrl
mutations at position 2058 (A2058C, A2058G, A2058T) or position 2059 (A2059C, A2059G). The remaining
M. abscessus
subsp.
massiliense
mutant showed an 18-bp repeat insertion in
rpIV
, encoding the L22 protein. Our results showed that acquisition of clarithromycin resistance is 100% mediated by structural 50S ribosomal subunit mutations for
M. abscessus
subsp.
abscessus
erm
(41) C28 and
M. abscessus
subsp.
massiliense
, whereas it is less common for
M. abscessus
subsp.
abscessus
erm
(41) T28 sequevar and
M. abscessus
subsp.
bolletii
, where other mechanisms may be responsible for failure.
Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine
Authors: Wand Matthew E. , Bock Lucy J. , Bonney Laura C. , Sutton J. Mark
Published: November 2016

Klebsiella pneumoniae
is an opportunistic pathogen that is often difficult to treat due to its multidrug resistance (MDR). We have previously shown that
K. pneumoniae
strains are able to “adapt” (become more resistant) to the widely used bisbiguanide antiseptic chlorhexidine. Here, we investigated the mechanisms responsible for and the phenotypic consequences of chlorhexidine adaptation, with particular reference to antibiotic cross-resistance. In five of six strains, adaptation to chlorhexidine also led to resistance to the last-resort antibiotic colistin. Here, we show that chlorhexidine adaptation is associated with mutations in the two-component regulator
phoPQ
and a putative Tet repressor gene (
smvR
) adjacent to the major facilitator superfamily (MFS) efflux pump gene,
smvA
. Upregulation of
smvA
(10- to 27-fold) was confirmed in
smvR
mutant strains, and this effect and the associated phenotype were suppressed when a wild-type copy of
smvR
was introduced on plasmid pACYC. Upregulation of
phoPQ
(5- to 15-fold) and
phoPQ
-regulated genes,
pmrD
(6- to 19-fold) and
pmrK
(18- to 64-fold), was confirmed in
phoPQ
mutant strains. In contrast, adaptation of
K. pneumoniae
to colistin did not result in increased chlorhexidine resistance despite the presence of mutations in
phoQ
and elevated
phoPQ
,
pmrD
, and
pmrK
transcript levels. Insertion of a plasmid containing
phoPQ
from chlorhexidine-adapted strains into wild-type
K. pneumoniae
resulted in elevated expression levels of
phoPQ
,
pmrD
, and
pmrK
and increased resistance to colistin, but not chlorhexidine. The potential risk of colistin resistance emerging in
K. pneumoniae
as a consequence of exposure to chlorhexidine has important clinical implications for infection prevention procedures.
In Vitro
-
In Vivo
Discordance with Humanized Piperacillin-Tazobactam Exposures against Piperacillin-Tazobactam-Resistant/Pan-β-Lactam-Susceptible Escherichia coli
Authors: Monogue M. L. , Nicolau D. P.
Published: November 2016

Recent findings have identified
Escherichia coli
strains that are pan-β-lactam susceptible (PBL-S) but piperacillin-tazobactam resistant (TZP-R)
in vitro
. We assessed the
in vivo
significance of this resistance profile in a neutropenic murine pneumonia model using humanized exposures of TZP with 18 clinical
E. coli
isolates, 8 TZP-S/PBL-S and 10 genotypically confirmed TZP-R/PBL-S. Despite phenotypically and genotypically defined resistance, TZP displayed efficacy against these isolates. Additional studies are required to define the clinical implications of these TZP-R/PBL-S strains.
Caged Garcinia Xanthones, a Novel Chemical Scaffold with Potent Antimalarial Activity
Authors: Ke Hangjun , Morrisey Joanne M. , Qu Shiwei , Chantarasriwong Oraphin , Mather Michael W. , Theodorakis Emmanuel A. , Vaidya Akhil B.
Published: November 2016

CagedGarciniaxanthones (CGXs) constitute a family of natural products that are produced by tropical/subtropical trees of the genusGarcinia. CGXs have a unique chemical architecture, defined by the presence of a caged scaffold at the C ring of a xanthone moiety, and exhibit a broad range of biological activities. Here we show that synthetic CGXs exhibit antimalarial activity againstPlasmodium falciparum, the causative parasite of human malaria, at the intraerythrocytic stages. Their activity can be substantially improved by attaching a triphenylphosphonium group at the A ring of the caged xanthone. Specifically, CR135 and CR142 were found to be highly effective antimalarial inhibitors, with 50% effective concentrations as low as ∼10 nM. CGXs affect malaria parasites at multiple intraerythrocytic stages, with mature stages (trophozoites and schizonts) being more vulnerable than immature rings. Within hours of CGX treatment, malaria parasites display distinct morphological changes, significant reduction of parasitemia (the percentage of infected red blood cells), and aberrant mitochondrial fragmentation. CGXs do not, however, target the mitochondrial electron transport chain, the target of the drug atovaquone and several preclinical candidates. CGXs are cytotoxic to human HEK293 cells at the low micromolar level, which results in a therapeutic window of around 150-fold for the lead compounds. In summary, we show that CGXs are potent antimalarial compounds with structures distinct from those of previously reported antimalarial inhibitors. Our results highlight the potential to further developGarcinianatural product derivatives as novel antimalarial agents.
Evaluation of MIC Strip Isavuconazole Test for Susceptibility Testing of Wild-Type and Non-Wild-Type Aspergillus fumigatus Isolates
Authors: Arendrup Maiken Cavling , Verweij Paul , Nielsen Henrik Vedel
Published: November 2016

We evaluated the MIC Strip Isavuconazole test against EUCAST E.Def 9.3 by using 40 wild-type and 39
CYP51A
mutant
Aspergillus fumigatus
strains. The strip full inhibition endpoint (FIE) and 80% growth inhibition endpoint were determined by two independent readers, reader 1 (R1) and R2. The essential (within ±0, ±1, and ±2 twofold dilutions) and categorical agreements were best with the FIE (for R1/R2, 42%/41%, 75%/73%, and 90%/89% for essential agreement, and 91.1%/92.4% categorical agreement, with 6.3/8.9% very major errors and 0/1.3% major errors, respectively). The MIC Strip Isavuconazole test with the FIE appears to be useful.
Population Pharmacokinetic Modeling To Estimate the Contributions of Genetic and Nongenetic Factors to Efavirenz Disposition
Authors: Robarge Jason D. , Metzger Ingrid F. , Lu Jessica , Thong Nancy , Skaar Todd C. , Desta Zeruesenay , Bies Robert R.
Published: November 2016

Efavirenz pharmacokinetics is characterized by large between-subject variability, which determines both therapeutic response and adverse effects. Some of the variability in efavirenz pharmacokinetics has been attributed to genetic variability in cytochrome P450 genes that alter efavirenz metabolism, such asCYP2B6andCYP2A6. While the effects of additional patient factors have been studied, such as sex, weight, and body mass index, the extent to which they contribute to variability in efavirenz exposure is inconsistently reported. The aim of this analysis was to develop a pharmacometric model to quantify the contribution of genetic and nongenetic factors to efavirenz pharmacokinetics. A population-based pharmacokinetic model was developed using 1,132 plasma efavirenz concentrations obtained from 73 HIV-seronegative volunteers administered a single oral dose of 600 mg efavirenz. A two-compartment structural model with absorption occurring by zero- and first-order processes described the data. Allometric scaling adequately described the relationship between fat-free mass and apparent oral clearance, as well as fat mass and apparent peripheral volume of distribution. Inclusion of fat-free mass and fat mass in the model mechanistically accounted for correlation between these disposition parameters and sex, weight, and body mass index. Apparent oral clearance of efavirenz was reduced by 25% and 51% in subjects predicted to have intermediate and slow CYP2B6 metabolizer status, respectively. The final pharmacokinetic model accounting for fat-free mass, fat mass, and CYP2B6 metabolizer status was consistent with known mechanisms of efavirenz disposition, efavirenz physiochemical properties, and pharmacokinetic theory. (This study has been registered at ClinicalTrials.gov under identifier NCT00668395.)
MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice
Authors: Yeruva Laxmi , Pouncey Dakota L. , Eledge Michael R. , Bhattacharya Sudeepa , Luo Chunqiao , Weatherford Erin W. , Ojcius David M. , Rank Roger G.
Published: November 2016

Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA) expression profile of the host, which, in turn, through regulation of the host inflammatory response, determines disease severity. Thus, we infected C57BL/6 mice with two populations of
Chlamydia muridarum
, each comprised of multiple genetic variants and differing in virulence: an attenuated strain (Nigg
A
) and a virulent strain (Nigg
V
). Nigg
A
and Nigg
V
elicited upper tract pathology in 54% and 91% of mice, respectively. miRNA expression analysis in Nigg
V
-infected mice showed significant downregulation of miRNAs involved in dampening fibrosis (miR-200b, miR-200b-5p, and 200b-3p miR-200a-3p) and in transcriptional regulation of cytokine responses (miR-148a-3p, miR-152-3p, miR-132, and miR-212) and upregulation of profibrotic miRNAs (miR-142, and miR-147). Downregulated miRNAs were associated with increased expression of interleukin 8 (IL-8), CXCL2, IL-1β, tumor necrosis factor alpha (TNF-α), and IL-6. Infection with Nigg
V
but not Nigg
A
led to decreased expression of Dicer and Ago 2, suggesting that Nigg
V
interaction with host cells inhibits expression of the miRNA biogenesis machinery, leading to increased cytokine expression and pathology.
Specific Human and Candida Cellular Interactions Lead to Controlled or Persistent Infection Outcomes during Granuloma-Like Formation
Authors: Misme-Aucouturier Barbara , Albassier Marjorie , Alvarez-Rueda Nidia , Le Pape Patrice
Published: November 2016

A delayed type of multicellular process could be crucial during chronic candidiasis in determining the course of infection. This reaction, consisting of organized immune cells surrounding the pathogen, initiates an inflammatory response to avoid fungal dissemination. The goal of the present study was to examine, at anin vitrocellular scale,Candidaand human immune cell interaction dynamics during a long-term period. By challenging human peripheral blood immune cells from 10 healthy donors with 32Candida albicansand non-albicans(C. glabrata,C. tropicalis,C. parapsilosis,C. dubliniensis,C. lusitaniae,C. krusei, andC. kefyr) clinical isolates, we showed thatCandidaspp. induced the formation of granuloma-like structures within 6 days after challenge, but their sizes and the respective fungal burdens differed according to theCandidaspecies. These two parameters are positively correlated. Phenotypic characteristics, such as hypha formation and higher axenic growth rate, seem to contribute to yeast persistence within granuloma-like structures. We showed an interindividual variability of the human response againstCandidaspp. Higher proportions of neutrophils and elevated CD4+/CD8+T cell ratios during the first days after challenge were correlated with early production of gamma interferon (IFN-γ) and associated with controlled infection. In contrast, the persistence ofCandidacould result from upregulation of proinflammatory cytokines such as interleukin-6 (IL-6), IFN-γ, and tumor necrosis factor alpha (TNF-α) and a poor anti-inflammatory negative feedback (IL-10). Importantly, regulatory subsets of NK cells and CD4loCD8hidoubly positive (DP) lymphocytes at late stage infiltrate granuloma-like structures and could correlate with the IL-10 and TNF-α production. These data offer a base frame to explain cellular events that guide infection control or fungal persistence.
Functional Impairment of Murine Dendritic Cell Subsets following Infection with Infective Larval Stage 3 of Brugia malayi
Authors: Sharma Aditi , Sharma Pankaj , Vishwakarma Achchhe Lal , Srivastava Mrigank
Published: November 2016

Filarial parasites cause functional impairment of host dendritic cells (DCs). However, the effects of early infection on individual DC subsets are not known. In this study, we infected BALB/c mice with infective stage 3 larvae of the lymphatic filarial parasite
Brugia malayi
(Bm-L3) and studied the effect on fluorescence-activated cell sorter (FACS)-sorted DC subsets. While myeloid DCs (mDCs) accumulated by day 3 postinfection (p.i.), lymphoid DCs (LDCs) and CD8
+
plasmacytoid DCs (pDCs) peaked at day 7 p.i. in the spleens and mesenteric lymph nodes (mLNs) of infected mice. Increased tumor necrosis factor alpha (TNF-α) but reduced interleukin 12 (IL-12) and Toll-like receptor 4 (TLR4), -6, and -9 and reciprocal secretion of IL-4 and IL-10 were also observed across all DC subsets. Interestingly, Bm-L3 increased the expression of CD80 and CD86 across all DC subsets but decreased that of major histocompatibility complex class II (MHC-II) on mDCs and pDCs, resulting in their impaired antigen uptake and presentation capacities, but maximally attenuated the T-cell proliferation capacity of only mDCs. Furthermore, Bm-L3 increased phosphorylated p38 (p-p38), but not p-ERK, in mDCs and LDCs but downregulated them in pDCs, along with differential modulation of protein tyrosine phosphatases SHP-1, TCPTP, PTEN, and PTP1B across all DC subsets. Taken together, we report hitherto undocumented effects of early Bm-L3 infection on purified host DC subsets that lead to their functional impairment and attenuated host T-cell response.
The ω Subunit Governs RNA Polymerase Stability and Transcriptional Specificity in Staphylococcus aureus
Authors: Weiss Andy , Moore Brittney D. , Tremblay Miguel H. J. , Chaput Dale , Kremer Astrid , Shaw Lindsey N.
Published: November 2016

Staphylococcus aureus
is a major human pathogen that causes infection in a wide variety of sites within the human body. Its ability to adapt to the human host and to produce a successful infection requires precise orchestration of gene expression. While DNA-dependent RNA polymerase (RNAP) is generally well characterized, the roles of several small accessory subunits within the complex have yet to be fully explored. This is particularly true for the omega (ω or RpoZ) subunit, which has been extensively studied in Gram-negative bacteria but largely neglected in Gram-positive counterparts. In
Escherichia coli
, it has been shown that ppGpp binding, and thus control of the stringent response, is facilitated by ω. Interestingly, key residues that facilitate ppGpp binding by ω are not conserved in
S. aureus
, and consequently, survival under starvation conditions is unaffected by
rpoZ
deletion. Further to this, ω-lacking strains of
S. aureus
display structural changes in the RNAP complex, which result from increased degradation and misfolding of the β′ subunit, alterations in δ and σ factor abundance, and a general dissociation of RNAP in the absence of ω. Through RNA sequencing analysis we detected a variety of transcriptional changes in the
rpoZ
-deficient strain, presumably as a response to the negative effects of ω depletion on the transcription machinery. These transcriptional changes translated to an impaired ability of the
rpoZ
mutant to resist stress and to fully form a biofilm. Collectively, our data underline, for the first time, the importance of ω for RNAP stability, function, and cellular physiology in
S. aureus
.

IMPORTANCE
In order for bacteria to adjust to changing environments, such as within the host, the transcriptional process must be tightly controlled. Transcription is carried out by DNA-dependent RNA polymerase (RNAP). In addition to its major subunits (α
2
ββ′) a fifth, smaller subunit, ω, is present in all forms of life. Although this small subunit is well studied in eukaryotes and Gram-negative bacteria, only limited information is available for Gram-positive and pathogenic species. In this study, we investigated the structural and functional importance of ω, revealing key roles in subunit folding/stability, complex assembly, and maintenance of transcriptional integrity. Collectively, our data underline, for the first time, the importance of ω for RNAP function and cellular harmony in
S. aureus
.
Ataxia telangiectasia: presentation and diagnostic delay
Authors: Devaney Rebecca , Pasalodos Sara , Suri Mohnish , Bush Andy , Bhatt Jayesh M
Published: November 2016

Background and aims

Ataxia telangiectasia (A-T) is a rare progressive, multisystem genetic disease. Families of children with ultra-rare diseases often experience significant diagnostic delays. We reviewed the diagnostic process for A-T in order to identify causes of delay in an attempt to facilitate earlier identification of A-T in the future.

Methods

A retrospective case note review of 79 children at the National Paediatric A-T clinic seen since May 2009. Data were collected on the nature and age of initial symptoms, the age at first presentation, measurement of alpha feto-protein (AFP) and age of genetic diagnostic confirmation.

Results

At presentation, 71 children (90%) had ataxia. The median presentation delay (from first parental concern to presentation) was 8 months (range 0–118 months), and the median diagnostic delay (genetic confirmation of diagnosis) was 12 months (range 1–109 months).

Conclusions

There are significant delays in presentation and diagnostic confirmation of A-T. A greater awareness of A-T and early measurement of AFP may help to improve this.
Estimating the weight of ethnically diverse children attending an Australian emergency department: a prospective, blinded, comparison of age-based and length-based tools including Mercy, PAWPER and Broselow
Authors: O'Leary Fenton , John-Denny Blessy , McGarvey Kathryn , Hann Alexandra , Pegiazoglou Ioannis , Peat Jennifer
Published: November 2016

Objective

To prospectively compare the actual weights of Australian children in an ethnically diverse metropolitan setting with the predicted weights using the Paediatric Advanced Weight Prediction in the Emergency Room (PAWPER) tape, Broselow tape, Mercy system and calculated weights using the updated Advanced Paediatric Life Support (APLS), Luscombe and Owens and Best Guess formulae.

Methods

A prospective, cross-sectional, observational, blinded, convenience study conducted at the Children's Hospital at Westmead Paediatric Emergency Department in Sydney, Australia. Comparisons were made using Bland-Altman plots, mean difference, limits of agreement and estimated weight within 10% and 20% of actual weight.

Results

199 patients were enrolled in the study with a mean actual weight of 27.2 kg (SD 17.2). Length-based tools, with or without body habitus adjustment, performed better than age-based formulae. When measuring estimated weight within 10% of actual weight, PAWPER performed best with 73%, followed by Mercy (69%), PAWPER with no adjustment (62%), Broselow (60%), Best Guess (47%), Luscombe and Owens (41%) and revised APLS (40%). Mean difference was similar across all methods ranging from 0.4 kg (0.0, 0.9) for Mercy to −2.2 kg (−3.5, −0.9) for revised APLS. Limits of agreement were narrower for the length-based tools (−5.9, 6.8 Mercy; −8.3, 5.6 Broselow; −9.0, 7.1 PAWPER adjusted; −12.1, 9.2 PAWPER unadjusted) than the age-based formulae (−18.6, 17.4 Best Guess; −19.4, 15.1 revised APLS, −21.8, 17.7 Luscombe and Owens).

Conclusion

In an ethnically diverse population, length-based methods with or without body habitus modification are superior to age-based methods for predicting actual body weight. Body habitus modifications increase the accuracy and precision slightly.
Developing a paediatric drug formulary for the Netherlands
Authors: van der Zanden Tjitske M , de Wildt Saskia N , Liem Yves , Offringa Martin , de Hoog Matthijs
Published: November 2016

As many drugs in paediatrics are used off-label, prescribers face a lack of evidence-based dosing guidelines. A Dutch framework was developed to provide dosing guidelines based on best available evidence from registration data, investigator-initiated research, professional guidelines, clinical experience and consensus. This has clarified the scientific grounds of drug use for children and encouraged uniformity in prescribing habits in the Netherlands. The developed framework and the current content of the Dutch Paediatric Formulary could be used as basis for similar initiatives worldwide, preferably in a concerted effort to ultimately provide children with effective and safe drug therapy.
Injection therapies for plantar fasciopathy (‘plantar fasciitis’): a systematic review and network meta-analysis of 22 randomised controlled trials
Authors: Tsikopoulos Konstantinos , Vasiliadis Haris S , Mavridis Dimitris
Published: November 2016

Objective

To compare the efficacy of different injection therapies for plantar fasciopathy (historically known as ‘plantar fasciitis’).

Design

Systematic review and network meta-analysis.

Data sources

Electronic databases (MEDLINE, CENTRAL, Web of Science and Scopus) were searched up to 11 July 2015 for completed studies.

Eligibility criteria for selecting studies

We considered randomised trials comparing various injection therapies in adults with plantar fasciopathy. The primary outcome was pain relief. Secondary outcomes included functional disability, composite and health-related outcomes. All outcomes were assessed (1) in the short term (up to 2 months), (2) the intermediate term (2–6 months) and (3) the medium term (more than 6 months to 2 years). Quality assessment was performed using the Cochrane risk of bias tool.

Results

We included 22 trials comprising 1216 patients. Dehydrated amniotic membrane injections were significantly superior to corticosteroids in the short term in achieving the primary and composite outcomes (mean difference (MD) in visual analogue scale (VAS) was −7.32, 95% CIs −11.2 to −3.38; and MD in the foot health status questionnaire was 31.2, 95% CIs 13.9 to 48.6, respectively). For pain relief, botulinum toxin-A provided a significant short-term advantage over placebo, which was still present at 6 months (MD in VAS was −2.9, 95% CIs −4.44 to −1.39; and MD −4.34, 95% CIs −7.18 to −1.54, respectively).

Although the dehydrated amniotic membrane provided significant clinical relief at 0–2 months, there were no data about this treatment at 2 months and beyond. Botulinum toxin-A injections significantly reduced pain intensity at 0–6 months.

Systematic review registration number

CRD42015017353.
Total sitting time and the risk of incident diabetes in Danish adults (the DANHES cohort) over 5 years: a prospective study
Authors: Petersen Christina B , Bauman Adrian , Tolstrup Janne S
Published: November 2016

Aims

To test the hypothesis that total sitting time is associated with incident diabetes, after adjustment for physical activity and obesity.

Methods

72 608 Danish adults from the DANHES cohort reported their total sitting time in 2007–2008 and were followed-up for 5 years, in relation to register-based incident diabetes mellitus. Cox regression analyses were used, and the effect-modifying influence of obesity and physical activity assessed.

Results

The age-sex adjusted HR for developing diabetes among those who sat 10+ h/day as compared to <6 h/day was 1.35 (95% CI 1.17 to 1.57). The relative risks were similar by gender, but were largely attenuated by adjustment for potential confounding factors including physical activity, and statistically non-significant for all categories of body mass index except the obese.

Conclusions

The association between total sitting time and incident diabetes is substantially moderated by physical activity and obesity. Total sitting time remains a risk factor for diabetes only in inactive and obese populations.
Cognitive capital, equity and child-sensitive social protection in Asia and the Pacific
Authors: Samson Michael , Fajth Gaspar , François Daphne
Published: November 2016

Promoting child development and welfare delivers human rights and builds sustainable economies through investment in ‘cognitive capital’. This analysis looks at conditions that support optimal brain development in childhood and highlights how social protection promotes these conditions and strengthens the achievement of the Sustainable Development Goals (SDGs) in Asia and the Pacific. Embracing child-sensitive social protection offers multiple benefits. The region has been a leader in global poverty reduction but the underlying pattern of economic growth exacerbates inequality and is increasingly unsustainable. The strategy of channelling low-skilled rural labour to industrial jobs left millions of children behind with limited opportunities for development. Building child-sensitive social protection and investing better in children's cognitive capacity could check these trends and trigger powerful long-term human capital development—enabling labour productivity to grow faster than populations age. While governments are investing more in social protection, the region's spending remains low by international comparison. Investment is particularly inadequate where it yields the highest returns: during the first 1000 days of life. Five steps are recommended for moving forward: (1) building cognitive capital by adjusting the region's development paradigms to reflect better the economic and social returns from investing in children; (2) understand and track better child poverty and vulnerability; (3) progressively build universal, child-sensitive systems that strengthen comprehensive interventions within life cycle frameworks; (4) mobilise national resources for early childhood investments and child-sensitive social protection; and (5) leverage the SDGs and other channels of national and international collaboration.
Patient engagement with infection management in secondary care: a qualitative investigation of current experiences
Authors: Rawson Timothy M , Moore Luke S P , Hernandez Bernard , Castro-Sanchez Enrique , Charani Esmita , Georgiou Pantelis , Ahmad Raheelah , Holmes Alison H
Published: November 2016

Objective

To understand patient engagement with decision-making for infection management in secondary care and the consequences associated with current practices.

Design

A qualitative investigation using in-depth focus groups.

Participants

Fourteen members of the public who had received antimicrobials from secondary care in the preceding 12 months in the UK were identified for recruitment. Ten agreed to participate. All participants had experience of infection management in secondary care pathways across a variety of South-East England healthcare institutes. Study findings were subsequently tested through follow-up focus groups with 20 newly recruited citizens.

Results

Participants reported feelings of disempowerment during episodes of infection in secondary care. Information is communicated in a unilateral manner with individuals ‘told’ that they have an infection and will receive an antimicrobial (often unnamed), leading to loss of ownership, frustration, anxiety and ultimately distancing them from engaging with decision-making. This poor communication drives individuals to seek information from alternative sources, including online, which is associated with concerns over reliability and individualisation. Failures in communication and information provision by clinicians in secondary care influence individuals’ future ideas about infections and their management. This alters their future actions towards antimicrobials and can drive prescription non-adherence and loss to follow-up.

Conclusions

Current infection management and antimicrobial prescribing practices in secondary care fail to engage patients with the decision-making process. Secondary care physicians must not view infection management episodes as discrete events, but as cumulative experiences which have the potential to shape future patient behaviour and understanding of antimicrobial use.
Federal actions to incentivise state adoption of 0.08 g/dL blood alcohol concentration laws
Authors: Tung Gregory J , Vernick Jon S , Stuart Elizabeth A , Webster Daniel W , Gielen Andrea C
Published: November 2016

Objective

To model rates of 0.08 g/dL blood alcohol concentration (BAC) per se law implementation among the states associated with (1) a federal incentive grant programme and (2) a threat from the federal government to withhold highway transportation funds.

Methods

An observational study of state-level 0.08 g/dL BAC per se law enactment among all 50 US states from 1982 to 2006 using a parametric survival analysis to assess the time-dependent risk of policy enactment.

Results

The federal government's threat to withhold transportation funds was associated with a 10.30 times greater hazard (HR: 10.30, 95% CI 3.88 to 27.36) of states adopting a 0.08 g/dL BAC law compared with periods of time when this threat was not in place. The incentive grant programme created by the federal government was associated with a non-significant 17% decrease in the hazard of states adopting a 0.08 g/dL BAC law (HR: 0.83, 95% CI 0.35 to 2.0).

Conclusion

In the case of 0.08 g/dL BAC per se laws, the federal government's threat to withhold transportation funds was effective at accelerating policy adoption.
Validation and verification of automated urine particle analysers
Authors: Bignardi Giuseppe Enrico
Published: November 2016

There is often uncertainty on how validation and verification of newly introduced tests should be conducted, and there is a real risk of verification becoming a meaningless ritual, rather than a useful exercise. This article reviews the literature and makes recommendations regarding the validation and verification of automated urine particles analysers. A generic practical approach to verification is also recommended. For many analysers, the accuracy of white blood cells, epithelial cells and bacterial counts is corroborated by a number of independent evaluations; thus, any verification laboratory work could be significantly scaled down. Conversely, in the scenario that automated urine microscopy is used as a screening test to reduce the number of urines cultured, the extremely variable performance reported in the literature requires a full-scale verification to define the optimal cut-off values that give a sensitivity of >98% with the local settings and circumstances. With some analysers, the risk of carry-over also needs to be assessed, as part of the verification process, and exclusion criteria (urines requiring culture regardless of the microscopy results) need to be well defined, as there are patients or specimen types for which the performance of microscopy as a screening test may not be adequate.
Cytographic changes on BC-6800 Haematological Analyzer related to the presence ofCandida albicansin peripheral blood. A new tool to suspect candidemia?
Authors: La Gioia Antonio , Devito Alessandra , Fiorini Fabiana , Bombara Maria , Isola Patrizia , Spinale Barbara , Francioni Lucia , Salamone Domenico , Marelli Paola , Buoro Sabrina , Fiorini Marcello
Published: November 2016

Background

We studied the quantitative and cytographic changes that the presence ofCandida albicans(C. albicans) in peripheral blood (PB) samples causes on the Mindray BC-6800 Haematological Analyzer.

Methods

A simulated in vitro candidemia was obtained by adding a different amount ofC. albicansto discarded remnants of PB samples. Quantitative data and cytographic features were evaluated immediately as well as after 120 and 240 min of the yeast addition. A microscopic slides review was even performed at the same time.

Results

After yeasts addition, an increase of total leucocytes, neutrophils and basophils have been observed, but these increases are not certainly descriptive ofC. albicanspresence.

Instead, extracellular blastospores cause a false increase in nucleated red blood cells (nRBCs), which appear as a new population in the specific counting channel for erytroblasts (NRBC channel). Regardless of the numbers,C. albicansform a pseudo-erythroblastic cluster in the NRBC channel whose resulting shape is so different than the ‘normal’ nRBC that it demands a microscopic review. Even cytographic changes related with the neutrophilic phagocytic activity have been observed on leucocyte's differential count citogram (DIFF) of the BC-6800.

Conclusions

Our observations suggest that the results of the BC-6800, which are due toC. albicans' presence, might be useful to speculate earlier diagnosis of sepsis.
Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with theNAB2-STAT6fusion gene
Authors: Kouba Erik , Simper Novae B , Chen Shaoxiong , Williamson Sean R , Grignon David J , Eble John N , MacLennan Gregory T , Montironi Rodolfo , Lopez-Beltran Antonio , Osunkoya Adeboye O , Zhang Shaobo , Wang Mingsheng , Wang Lisha , Tran Thu , Emerson Robert E , Baldrige Lee Ann , Monn M Francesca , Linos Konstantinos , Cheng Liang
Published: November 2016

Aims

To characterise clinicopathological features and clinical outcomes of the genitourinary tract solitary fibrous tumours, incorporatingNAB2-STAT6gene fusion status.

Methods

The presence of the molecular hallmarkNAB2-STAT6gene fusion and for the defining fusion partner product STAT6 was assessed in 11 cases of the genitourinary tract solitary fibrous tumours.NAB2-STAT6gene fusion analysis was performed using a break-apart fluorescence in situ hybridisation (FISH) probe using a probe cocktail with Bacterial artificial chromosome (BAC) clones forSTAT6andNAB2.

Results

Eleven solitary fibrous tumours were diagnosed in eight male patients and three female patients with a mean age of 46 years (range: 11–64 years). Four of the tumours had malignant histological features, and three were considered moderate risk for metastasis. With a mean follow-up time of 61 months, 1 recurred locally and 2 presented at distant metastatic sites. Using a break-apart FISH probe cocktail, we found theNAB2-STAT6gene fusion and nuclear STAT6 expression in 58% and 91% of cases, respectively. However, theNAB2-STAT6fusion status was not correlated with STAT6 expression or useful in discriminating between malignant histological features or subsequent clinical outcomes in the genitourinary solitary fibrous tumours.

Conclusions

A subset of solitary fibrous tumours of the genitourinary tract behaved aggressively. Using a break-apart FISH probe cocktail, we found theNAB2-STAT6gene fusion in 64% of cases. However, theNAB2-STAT6fusion status was not correlated with STAT6 expression or useful in discriminating between low-risk or high-risk tumours and subsequent clinical outcomes.