bluuebunny/crossref_metadata_2025 huggingface dataset:
Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome
bc
1
Inhibition Strategy for Malaria
Authors: Stickles Allison M. , Smilkstein Martin J. , Morrisey Joanne M. , Li Yuexin , Forquer Isaac P. , Kelly Jane X. , Pou Sovitj , Winter Rolf W. , Nilsen Aaron , Vaidya Akhil B. , Riscoe Michael K.
Published: June 2016

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant
Plasmodium
parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome

bc
1

complex (cyt

bc
1

) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt

bc
1

: atovaquone (ATV) blocks the quinol oxidase (Q
o
) site of cyt

bc
1

, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Q
i
) site and retain full potency against ATV-resistant
Plasmodium falciparum
strains with Q
o
site mutations. Here, we provide the first
in vivo
comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using
P. yoelii
murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt

bc
1

is a valuable strategy for antimalarial combination therapy and that Q
i
site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Q
o
site inhibitor ATV.
Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy
Authors: Roger Claire , Wallis Steven C. , Muller Laurent , Saissi Gilbert , Lipman Jeffrey , Lefrant Jean-Yves , Roberts Jason A.
Published: June 2016

The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h
−1
for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h
−1
for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (
C
max
)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.)
Chelation of Membrane-Bound Cations by Extracellular DNA Activates the Type VI Secretion System in Pseudomonas aeruginosa
Authors: Wilton Mike , Wong Megan J. Q. , Tang Le , Liang Xiaoye , Moore Richard , Parkins Michael D. , Lewenza Shawn , Dong Tao G.
Published: June 2016

Pseudomonas aeruginosaemploys its type VI secretion system (T6SS) as a highly effective and tightly regulated weapon to deliver toxic molecules to target cells. T6SS-secreted proteins ofP. aeruginosacan be detected in the sputum of cystic fibrosis (CF) patients, who typically present a chronic and polymicrobial lung infection. However, the mechanism of T6SS activation in the CF lung is not fully understood. Here we demonstrate that extracellular DNA (eDNA), abundant within the CF airways, stimulates the dynamics of the H1-T6SS cluster apparatus inPseudomonas aeruginosaPAO1. Addition of Mg2+or DNase with eDNA abolished such activation, while treatment with EDTA mimicked the eDNA effect, suggesting that the eDNA-mediated effect is due to chelation of outer membrane-bound cations. DNA-activated H1-T6SS enablesP. aeruginosato nonselectively attack neighboring species regardless of whether or not it was provoked. Because of the importance of the T6SS in interspecies interactions and the prevalence of eDNA in the environments thatP. aeruginosainhabits, our report reveals an important adaptation strategy that likely contributes to the competitive fitness ofP. aeruginosain polymicrobial communities.
Glucosylation Drives the Innate Inflammatory Response to Clostridium difficile Toxin A
Authors: Cowardin Carrie A. , Jackman Brianna M. , Noor Zannatun , Burgess Stacey L. , Feig Andrew L. , Petri William A.
Published: June 2016

Clostridium difficileis a major, life-threatening hospital-acquired pathogen that causes mild to severe colitis in infected individuals. The tissue destruction and inflammation which characterizeC. difficileinfection (CDI) are primarily due to the Rho-glucosylating toxins A and B. These toxins cause epithelial cell death and induce robust inflammatory signaling by activating the transcription factor NF-κB, leading to chemokine and cytokine secretion. The toxins also activate the inflammasome complex, which leads to secretion of the pyrogenic cytokine IL-1β. In this study, we utilized glucosylation-deficient toxin A to show that activation of the inflammasome by this toxin is dependent on Rho glucosylation, confirming similar findings reported for toxin B. We also demonstrated that tissue destruction andin vivoinflammatory cytokine production are critically dependent on the enzymatic activity of toxin A, suggesting that inhibiting toxin glucosyltransferase activity may be effective in combating this refractory disease.
Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract
Authors: Dai Jin , Zhang Tianyuan , Wang Luying , Shao Lili , Zhu Cuiming , Zhang Yuyang , Failor Courtney , Schenken Robert , Baseman Joel , He Cheng , Zhong Guangming
Published: June 2016

Chlamydiahas been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown thatChlamydia muridarumspreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenousC. muridarumcan spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressingC. muridarumstrain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. Theex vivoimaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of theC. muridarumorganisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenousC. muridaruminoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract.
Microfluidic Studies of Biofilm Formation in Dynamic Environments
Authors: Yawata Yutaka , Nguyen Jen , Stocker Roman , Rusconi Roberto
Published: June 2016

The advent of microscale technologies, such as microfluidics, has revolutionized many areas of biology yet has only recently begun to impact the field of bacterial biofilms. By enabling accurate control and manipulation of physical and chemical conditions, these new microscale approaches afford the ability to combine important features of natural and artificial microbial habitats, such as fluid flow and ephemeral nutrient sources, with an unprecedented level of flexibility and quantification. Here, we review selected case studies to exemplify this potential, discuss limitations, and suggest that this approach opens new vistas into biofilm research over traditional setups, allowing us to expand our understanding of the formation and consequences of biofilms in a broad range of environments and applications.
Seminal Plasma Promotes Neisseria gonorrhoeae Aggregation and Biofilm Formation
Authors: Anderson Mark T. , Byerly Luke , Apicella Michael A. , Seifert H. Steven
Published: June 2016

Neisseria gonorrhoeae
causes the human-specific disease gonorrhea and is transmitted from person to person primarily via sexual contact. During transmission,
N. gonorrhoeae
is often exposed to seminal fluid and must adapt to this change in environment. Previous work demonstrated that seminal fluid facilitates
N. gonorrhoeae
motility and alters epithelial cell interactions. In this study, exposure to seminal fluid was found to decrease surface adherence of gonococci in a manner that was independent of Opa adhesin proteins or type IV pilus retraction. Semen was also shown to cause dispersal of bacteria that had previously established surface adherence. Although surface adherence decreased, interbacterial interactions were increased by seminal plasma both in long-term static culture and on a cell-to-cell basis over shorter time periods. The result of increased bacterium-bacterium interactions resulted in the formation of microcolonies, an important step in the
N. gonorrhoeae
infectious process. Seminal fluid also facilitated increased bacterial aggregation in the form of shear-resistant three-dimensional biofilms. These results emphasize the importance of the gonococcal response to the influx of seminal fluid within the genital niche. Further characterization of the
N. gonorrhoeae
response to semen will advance our understanding of the mechanisms behind the establishment of infection in naive hosts and the process of transmission.

IMPORTANCE
N. gonorrhoeae
is the causative agent of the globally prevalent sexually transmitted infection gonorrhea. An understudied aspect of this human-adapted pathogen is the change in bacterial physiology that occurs during sexual transmission.
N. gonorrhoeae
encounters semen when transmitted from host to host, and it is known that, when
N. gonorrhoeae
is exposed to seminal fluid, alterations in bacterial motility and type IV pilus arrangement occur. This work extends our previous observations on this modulation of gonococcal physiology by seminal fluid and demonstrates that seminal plasma decreases surface adherence, promotes interbacterial interactions, and enhances biofilm formation.
The
SMUL_1544
Gene Product Governs Norcobamide Biosynthesis in the Tetrachloroethene-Respiring Bacterium Sulfurospirillum multivorans
Authors: Keller Sebastian , Treder Aaron , von Reuss Stephan H. , Escalante-Semerena Jorge C. , Schubert Torsten
Published: June 2016

The tetrachloroethene (PCE)-respiring bacterium
Sulfurospirillum multivorans
produces a unique cobamide, namely, norpseudo-B
12
, which, in comparison to other cobamides, e.g., cobalamin and pseudo-B
12
, lacks the methyl group in the linker moiety of the nucleotide loop. In this study, the protein SMUL_1544 was shown to be responsible for the formation of the unusual linker moiety, which is most probably derived from ethanolamine-phosphate (EA-P) as the precursor. The product of the
SMUL_1544
gene successfully complemented a
Salmonella enterica
Δ
cobD
mutant. The
cobD
gene encodes an
l
-threonine-
O
-3-phosphate (
l
-Thr-P) decarboxylase responsible for the synthesis of (
R
)-1-aminopropan-2-ol
O
-2-phosphate (AP-P), required specifically for cobamide biosynthesis. When SMUL_1544 was produced in the heterologous host lacking CobD, norpseudo-B
12
was formed, which pointed toward the formation of EA-P rather than AP-P. Guided cobamide biosynthesis experiments with minimal medium supplemented with
l
-Thr-P supported cobamide biosynthesis in
S. enterica
producing SMUL_1544 or
S. multivorans
. Under these conditions, both microorganisms synthesized pseudo-B
12
. This observation indicated a flexibility in the SMUL_1544 substrate spectrum. From the formation of catalytically active PCE reductive dehalogenase (PceA) in
S. multivorans
cells producing pseudo-B
12
, a compatibility of the respiratory enzyme with the cofactor was deduced. This result might indicate a structural flexibility of PceA in cobamide binding. Feeding of
l
-[3-
13
C]serine to cultures of
S. multivorans
resulted in isotope labeling of the norpseudo-B
12
linker moiety, which strongly supports the hypothesis of EA-P formation from
l
-serine-
O
-phosphate (
l
-Ser-P) in this organism.

IMPORTANCE
The identification of the gene product SMUL_1544 as a putative
l
-Ser-P decarboxylase involved in norcobamide biosynthesis in
S. multivorans
adds a novel module to the assembly line of cobamides (complete corrinoids) in prokaryotes. Selected cobamide-containing enzymes (e.g., reductive dehalogenases) showed specificity for their cobamide cofactors. It has recently been proposed that the structure of the linker moiety of norpseudo-B
12
and the mode of binding of the EA-P linker to the PceA enzyme reflect the high specificity of the enzyme for its cofactor. Data reported herein do not support this idea. In fact, norpseudo-B
12
was functional in the cobamide-dependent methionine biosynthesis of
S. enterica
, raising questions about the role of norcobamides in nature.
Essential Genes Predicted in the Genome of Rubrivivax gelatinosus
Authors: Curtis Patrick D.
Published: June 2016

Rubrivivax gelatinosus
is a betaproteobacterium with impressive metabolic diversity. It is capable of phototrophy, chemotrophy, two different mechanisms of sugar metabolism, fermentation, and H
2
gas production. To identify core essential genes,
R. gelatinosus
was subjected to saturating transposon mutagenesis and high-throughput sequencing (TnSeq) analysis using nutrient-rich, aerobic conditions. Results revealed that virtually no primary metabolic genes are essential to the organism and that genomic redundancy only explains a portion of the nonessentiality, but some biosynthetic pathways are still essential under nutrient-rich conditions. Different essentialities of different portions of the Pho regulatory pathway suggest that overexpression of the regulon is toxic and hint at a larger connection between phosphate regulation and cellular health. Lastly, various essentialities of different tRNAs hint at a more complex situation than would be expected for such a core process. These results expand upon research regarding cross-organism gene essentiality and further enrich the study of purple nonsulfur bacteria.

IMPORTANCE
Microbial genomic data are increasing at a tremendous rate, but physiological characterization of those data lags far behind. One mechanism of high-throughput physiological characterization is TnSeq, which uses high-volume transposon mutagenesis and high-throughput sequencing to identify all of the essential genes in a given organism's genome. Here TnSeq was used to identify essential genes in the metabolically versatile betaproteobacterium
Rubrivivax gelatinosus
. The results presented here add to the growing TnSeq field and also reveal important aspects of
R. gelatinosus
physiology, which are applicable to researchers working on metabolically flexible organisms.
Rare case of stress cardiomyopathy due to intramuscular epinephrine administration
Authors: Nazir Salik , Melnick Stephen , Lohani Saroj , Lloyd Benjamin
Published: June 2016

We report a case of a 37-year-old woman who presented to our hospital with retrosternal chest pain following intramuscular administration of epinephrine due to presumed anaphylaxis. On arrival, she was found to have ST segment depression in the anterolateral leads on ECG and elevated cardiac troponins. She was diagnosed with stress cardiomyopathy based on left ventricle dysfunction and angiographically normal coronary arteries on cardiac catheterisation. To the best of our knowledge, this is the third reported case of takotsubo cardiomyopathy following appropriately dosed intramuscular administration of epinephrine for anaphylaxis. This case highlights the importance of considering stress cardiomyopathy in patients presenting with chest pain syndrome following systemic administration of epinephrine.
Validation of the Kinyarwanda-version Short-Form Leeds Dyspepsia Questionnaire and Short-Form Nepean Dyspepsia Index to assess dyspepsia prevalence and quality-of-life impact in Rwanda
Authors: Nkurunziza Arcade , Dusabejambo Vincent , Everhart Kelly , Bensen Steve , Walker Tim
Published: June 2016

Objectives

We aimed to develop and validate Kinyarwanda versions of Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) and Short-Form Nepean Dyspepsia Index (SF-NDI) to measure the frequency and severity of dyspepsia and associated quality-of-life impact in Rwanda.

Setting

A single, tertiary care centre in Rwanda.

Participants

200 consecutive Kinyarwanda-speaking patients referred to endoscopy (100 patients) or medical outpatients (100 patients).

Interventions

Kinyarwanda versions of the SF-LDQ and SF-NDI were developed from English versions by translation, with back translation, crosschecking and pilot testing. Study participants completed these questionnaires at enrolment (time 1), and then completed the surveys again with blinded phone interviewers 3 days later (time 2). 20 randomly selected participants, diagnosed with a peptic ulcer on index endoscopy, completed a third survey by phone at day 30 (time 3), after therapy.

Primary outcome measures

Internal consistency at time 1 (by Cronbach's α) and test–retest reliability between time 1 and time 2 (Spearman's correlation coefficient) for translated SF-LDQ and SF-NDI; validity versus clinical diagnosis (by receiver operating characteristic (ROC) curve) and responsiveness to treatment for SF-LDQ (by change in mean score). All outcomes were measured as per protocol.

Results

Cronbach's α of the translated SF-LDQ was 0.93, showing high internal consistency. Spearman's correlation coefficient comparing time 1 and time 2 was 0.978 (p<0.001), demonstrating high reliability. Cronbach's α for the translated SF-NDI was 0.92. A cut-off score of 16 on the SF-LDQ showed a sensitivity of 97% and a specificity of 71% for the diagnosis of dyspepsia, correctly classifying 89% of patients. In the responsiveness analysis, the mean SF-LDQ score was reduced from 20.1 prior to treatment to 13.9 after 30 days of treatment (p=0.003).

Conclusions

The Kinyarwanda versions of the SF-LDQ and SF-NDI were valid, reliable and responsive to treatment.
Clinical outcomes at 12 months and risk of inflammatory bowel disease in patients with an intermediate raised fecal calprotectin: a ‘real-world’ view
Authors: McFarlane Michael , Chambers Samantha , Malik Ahmad , Lee Bee , Sung Edmond , Nwokolo Chuka , Waugh Norman , Arasaradnam Ramesh
Published: June 2016

Objectives

A recent systematic review confirmed the usefulness of fecal calprotectin (FC) in distinguishing organic (inflammatory bowel disease (IBD)) from non-organic gastrointestinal disease (irritable bowel syndrome (IBS)). FC levels <50 μg/g have a negative predictive value >92% to exclude organic gastrointestinal (GI) disease. Levels >250 μg/g correlate with endoscopic IBD disease activity; sensitivity 90%. We aimed to determine clinical outcomes in intermediate raised FC results (50–250 μg/g).

Setting

Primary care general practices in Coventry and Warwickshire, and 3 secondary care hospitals.

Participants

443 FC results in adults (>16 years old) were reviewed from July 2012 to October 2013. Clinical data was collected from hospital databases and general practitioners. Long-term clinical data was available in 41 patients (out of 48).

Primary and secondary outcome measures

The number of new diagnoses of IBD, IBS and other diagnoses for the intermediate group. The number referred and discharged from secondary care.

Results

A new IBD diagnosis was made in 19% (n=8) of intermediate results (1% of normal and 38% of raised results). 5% (n=2) of intermediate results had known IBD in remission. A new IBS diagnosis was made in 27% (n=11) of intermediate results, while 34% (n=14) remained undiagnosed, although 8 of these were not referred to secondary care.

Conclusions

FC testing remains useful in aiding diagnosis of organic GI conditions. However, unlike negative and strongly positive FC results, intermediate FC results lead to a mixture of diagnoses. The OR of a new diagnosis of IBD for an intermediate result compared to normal FC result was 26.6, while an intermediate FC result gave an OR of 0.54 for a new IBS diagnosis compared to normal FC. For intermediate FC results, 1 in 3 patients remained in secondary care after 12 months with an OR of 3.6 compared to a normal FC result.
Effect of affordable technology on physical activity levels and mobility outcomes in rehabilitation: a protocol for the Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial
Authors: Hassett Leanne , van den Berg Maayken , Lindley Richard I , Crotty Maria , McCluskey Annie , van der Ploeg Hidde P , Smith Stuart T , Schurr Karl , Killington Maggie , Bongers Bert , Howard Kirsten , Heritier Stephane , Togher Leanne , Hackett Maree , Treacy Daniel , Dorsch Simone , Wong Siobhan , Scrivener Katharine , Chagpar Sakina , Weber Heather , Pearson Ross , Sherrington Catherine
Published: June 2016

Introduction

People with mobility limitations can benefit from rehabilitation programmes that provide a high dose of exercise. However, since providing a high dose of exercise is logistically challenging and resource-intensive, people in rehabilitation spend most of the day inactive. This trial aims to evaluate the effect of the addition of affordable technology to usual care on physical activity and mobility in people with mobility limitations admitted to inpatient aged and neurological rehabilitation units compared to usual care alone.

Methods and analysis

A pragmatic, assessor blinded, parallel-group randomised trial recruiting 300 consenting rehabilitation patients with reduced mobility will be conducted. Participants will be individually randomised to intervention or control groups. The intervention group will receive technology-based exercise to target mobility and physical activity problems for 6 months. The technology will include the use of video and computer games/exercises and tablet applications as well as activity monitors. The control group will not receive any additional intervention and both groups will receive usual inpatient and outpatient rehabilitation care over the 6-month study period. The coprimary outcomes will be objectively assessed physical activity (proportion of the day spent upright) and mobility (Short Physical Performance Battery) at 6 months after randomisation. Secondary outcomes will include: self-reported and objectively assessed physical activity, mobility, cognition, activity performance and participation, utility-based quality of life, balance confidence, technology self-efficacy, falls and service utilisation. Linear models will assess the effect of group allocation for each continuously scored outcome measure with baseline scores entered as a covariate. Fall rates between groups will be compared using negative binomial regression. Primary analyses will be preplanned, conducted while masked to group allocation and use an intention-to-treat approach.

Ethics and dissemination

The protocol has been approved by the relevant Human Research Ethics Committees and the results will be disseminated widely through peer-reviewed publication and conference presentations.

Trial registration number

ACTRN12614000936628. Pre-results.
Using lean methodology to improve efficiency of electronic order set maintenance in the hospital
Authors: Idemoto Lori , Williams Barbara , Blackmore Craig
Published: June 2016

Order sets, a series of orders focused around a diagnosis, condition, or treatment, can reinforce best practice, help eliminate outdated practice, and provide clinical guidance. However, order sets require regular updates as evidence and care processes change. We undertook a quality improvement intervention applying lean methodology to create a systematic process for order set review and maintenance.

Root cause analysis revealed challenges with unclear prioritization of requests, lack of coordination between teams, and lack of communication between producers and requestors of order sets. In March of 2014, we implemented a systematic, cyclical order set review process, with a set schedule, defined responsibilities for various stakeholders, formal meetings and communication between stakeholders, and transparency of the process.

We first identified and deactivated 89 order sets which were infrequently used. Between March and August 2014, 142 order sets went through the new review process. Processing time for the build duration of order sets decreased from a mean of 79.6 to 43.2 days (p<.001, CI=22.1, 50.7).

Applying Lean production principles to the order set review process resulted in significant improvement in processing time and increased quality of orders. As use of order sets and other forms of clinical decision support increase, regular evidence and process updates become more critical.
Standardised incidence ratios (SIRs) for cancer after renal transplant in systemic lupus erythematosus (SLE) and non-SLE recipients
Authors: Ramsey-Goldman Rosalind , Brar Amarpali , Richardson Carrie , Salifu Moro O , Clarke Ann , Bernatsky Sasha , Stefanov Dimitre G , Jindal Rahul M
Published: June 2016

Objective

We investigated malignancy risk after renal transplantation in patients with and without systemic lupus erythematosus (SLE).

Methods

Using the United States Renal Data System from 2001 to 2009, 143 652 renal transplant recipients with and without SLE contributed 585 420 patient-years of follow-up to determine incident cancers using Medicare claims codes. We calculated standardised incidence ratios (SIRs) of cancer by group using age, sex, race/ethnicity-specific and calendar year-specific cancer rates compared with the US population.

Results

10 160 cancers occurred at least 3 months after renal transplant. Overall cancer risk was increased in both SLE and non-SLE groups compared with the US general population, SIR 3.5 (95% CI 2.1 to 5.7) and SIR 3.7 (95% CI 2.4 to 5.7), respectively. Lip/oropharyngeal, Kaposi, neuroendocrine, thyroid, renal, cervical, lymphoma, liver, colorectal and breast cancers were increased in both groups, whereas only melanoma was increased in SLE and lung cancer was increased in non-SLE. In Cox regression analysis, SLE status (HR 1.1, 95% CI 0.9 to 1.3) was not associated with increased risk of developing cancer, adjusted for other independent risk factors for developing cancer in renal transplant recipients. We found that smoking (HR 2.2, 95% CI 1.2 to 4.0), cytomegalovirus positivity at time of transplant (HR 1.3, 95% CI 1.2 to 1.4), white race (HR 1.2, 95% CI 1.2 to 1.3) and older recipient age at time of transplantation (HR 1.0 95% CI 1.0 to 1.2) were associated with an increased risk for development of cancer, whereas shorter time on dialysis, Epstein-Barr virus or HIV were associated with a lower risk for development of cancer.

Conclusions

Cancer risk in renal transplant recipients appeared similar in SLE and non-SLE subjects, aside from melanoma. Renal transplant recipients may need targeted counselling regarding surveillance and modifiable risk factors.
Comparison of the hydrological role of two reclaimed slopes of different ages in the Athabasca oil sands region, Alberta, Canada
Authors: Ketcheson Scott J. , Price Jonathan S.
Published: June 2016

Establishing hydrological connectivity in reconstructed landscapes, and understanding how this connectivity evolves over time, is critical for the development of effective water management strategies after oil sands extraction. In the current study, the dominant controls on the soil water regimes and runoff generation mechanisms on two contrasting reclaimed slopes (2 and 6 years after reclamation) in the Athabasca oil sands region are investigated. The most recently reclaimed slope demonstrated a hydrologic regime with limited soil water storage due to a low surface infiltration capacity that constrained percolation of rainfall. Accordingly, this slope generated a substantial amount of surface runoff controlled primarily by precipitation intensity. Conversely, the older slope had a greater surface infiltration capacity, more dynamic soil water regime, and infrequent surface runoff. Topography controlled soil water distribution on the older slope more strongly than the newer slope due to more efficient water redistribution. This suggests that changes in the hydrophysical properties of reclamation materials following construction result in a shift in the hydrological role of reclaimed slopes at the watershed scale. Thus, over time, reclaimed slopes produce less overland flow and shift from water conveyors to water storage features in constructed watershed systems.
First estimates of the probability of survival in a small-bodied, high-elevation frog (Boreal Chorus Frog,Pseudacrismaculata), or how historical data can be useful
Authors: Muths E. , Scherer R.D. , Amburgey S.M. , Matthews T. , Spencer A.W. , Corn P.S.
Published: June 2016

In an era of shrinking budgets yet increasing demands for conservation, the value of existing (i.e., historical) data are elevated. Lengthy time series on common, or previously common, species are particularly valuable and may be available only through the use of historical information. We provide first estimates of the probability of survival and longevity (0.67–0.79 and 5–7 years, respectively) for a subalpine population of a small-bodied, ostensibly common amphibian, the Boreal Chorus Frog (Pseudacris maculata (Agassiz, 1850)), using historical data and contemporary, hypothesis-driven information–theoretic analyses. We also test a priori hypotheses about the effects of color morph (as suggested by early reports) and of drought (as suggested by recent climate predictions) on survival. Using robust mark–recapture models, we find some support for early hypotheses regarding the effect of color on survival, but we find no effect of drought. The congruence between early findings and our analyses highlights the usefulness of historical information in providing raw data for contemporary analyses and context for conservation and management decisions.
Symmetry properties of conservation laws
Authors: Anco Stephen C.
Published: June 2016

Symmetry properties of conservation laws of partial differential equations are developed by using the general method of conservation law multipliers. As main results, simple conditions are given for characterizing when a conservation law and its associated conserved quantity are invariant (and, more generally, homogeneous) under the action of a symmetry. These results are used to show that a recent conservation law formula (due to Ibragimov) is equivalent to a standard formula for the action of an infinitesimal symmetry on a conservation law multiplier.
Chain mapping approach of Hamiltonian for FMO complex using associated, generalized and exceptional Jacobi polynomials
Authors: Mahdian M. , Arjmandi M. B. , Marahem F.
Published: June 2016

The excitation energy transfer (EET) in photosynthesis complex has been widely investigated in recent years. However, one of the main problems is simulation of this complex under realistic condition. In this paper by using the associated, generalized and exceptional Jacobi polynomials, firstly, we introduce the spectral density of Fenna–Matthews–Olson (FMO) complex. Afterward, we obtain a map that transforms the Hamiltonian of FMO complex as an open quantum system to a one-dimensional chain of oscillatory modes with only nearest neighbor interaction in which the system is coupled only to first mode of chain. The frequency and coupling strength of each mode can be analytically obtained from recurrence coefficient of mentioned orthogonal polynomials.
Numeric Solutions of Dirac–Gursey Spinor Field Equation Under External Gaussian White Noise
Authors: Aydogmus Fatma
Published: June 2016

In this paper, we consider the Dirac-Gursey spinor field equation that has particle-like solutions derived classical field equations so-called instantons, formed by using Heisenberg ansatz, under the effect of an additional Gaussian white noise term. Our purpose is to understand how the behavior of spinor-type excited instantons in four dimensions can be affected by noise. Thus, we simulate the phase portraits and Poincaré sections of the obtained system numerically both with and without noise. Recurrence plots are also given for more detailed information regarding the system.
An Exploratory-Comparative Study of Implementation Success Factors for MSS/DMSS and MIS
Authors: Mora Manuel , Phillips-Wren Gloria , Wang Fen , Gelman Ovsei
Published: June 2016

This research paper presents a novel complementary approach to the system implementation research stream by comparing implementation success factors for management support systems (MSS), also called decision-making support systems, (DMSS) and management information systems (MIS). Data were collected over a 14-year period from 132 information technology (IT) practitioners from an industrialized region in Mexico and analyzed using exploratory factor analysis (EFA). While implementation success factors for MSS/DMSS and MIS have been studied previously, few comparative studies have been reported. Differences in implementation success factors between MSS/DMSS and MIS were found. Three clearly identified implementation success factors were found for MIS (i.e., project management, organizational feasibility and IT resources), and two factors emerged for MSS/DMSS with mixed items (i.e., system-organization-technical feasibility, and alignment between users, team, system and organization). The results indicate that achieving MSS/DMSS implementation success is more complex than for MIS. Although exploratory in nature, the comparative differences offer guidance to IT practitioners in implementing such systems and contribute to the MSS/DMSS literature with insights on implementation success factors that are unique to this type of IT system.
Non-R&D Innovation Patterns in Chinese SMEs: An Empirical Study from Zhejiang Province
Authors: Zheng Gang , Guo Yanting , Wang Yajuan
Published: June 2016

During the last few decades, research and development (R&D) have always been regarded as the most important or even the only factor in the attempt to explain the innovation capability and performance of enterprises, industries and economies, while to a large extent, those heterogeneous innovation activities beyond formal R&D are ignored or underestimated. Some research has shown that non-R&D innovation activities contribute to make full use of resources beyond R&D to promote performance, especially to small- and medium-sized enterprises (SMEs) with weak R&D capability. However, non-R&D innovators’ behavior is still a black box by far, and especially few empirical research have been conducted in China context. This paper first explores the heterogeneous innovation patterns of non-R&D innovation by survey among Chinese SMEs in Zhejiang Province. It shows that, product and service customization, imitation and design, technology adoption and incremental modification, organizational innovation and marketing innovation are the main patterns of non-R&D innovation in China. Then, a case study is followed to cross-validate the patterns and relationships between non-R&D innovation and growth of SMEs in China. Generally, this study has implications for both academia and policy-makers. As it demonstrates, non-R&D innovation is an effective way for SMEs to quickly grow and sustain competitiveness in competition. On the other hand, this study helps to optimize some of current innovation policies for SMEs in China, where policy incentives are mainly R&D-focused. It also likely sheds light on the SMEs in other emerging economies.
A note on para-holomorphic Riemannian–Einstein manifolds
Authors: Ida Cristian , Ionescu Alexandru , Manea Adelina
Published: June 2016

The aim of this note is the study of Einstein condition for para-holomorphic Riemannian metrics in the para-complex geometry framework. First, we make some general considerations about para-complex Riemannian manifolds (not necessarily para-holomorphic). Next, using a one-to-one correspondence between para-holomorphic Riemannian metrics and para-Kähler–Norden metrics, we study the Einstein condition for a para-holomorphic Riemannian metric and the associated real para-Kähler–Norden metric on a para-complex manifold. Finally, it is shown that every semi-simple para-complex Lie group inherits a natural para-Kählerian–Norden Einstein metric.
Architecture Optimization Model for the Probabilistic Self-Organizing Maps and Speech Compression
Authors: En-Naimani Zakariae , Lazaar Mohamed , Ettaouil Mohamed
Published: June 2016

The probabilistic self-organizing map (PRSOM) is an improved version of the Kohonen classical model (SOM) that appeared in the late 1990’s. In the last years, the interest of probabilistic methods, especially in the fields of clustering and classification has increased, and the PRSOM has been successfully employed in many technological uses, such as: pattern recognition, speech recognition, data compression, medical diagnosis, etc. Mathematically, the PRSOM gives an estimation of the density probability function of a set of samples. And this estimation depends on the parameters given by the architecture of the model. Therefore, the main problem of this model, that we try to approach in this paper, is the architecture choice (the number of neurons and the initialization parameters). In summary, in the present paper, we describe a recent approach of PRSOM trying to find a solution to the problem below. For that, we propose an architecture optimization model that is a mixed integer nonlinear optimization model under linear constraints, resolved by the genetic algorithm. Then to prove the efficiency of the proposed model, we chose to apply it on a speech compression technique based on the determination of the optimal codebook, and finally, we give an implementation and an evaluation of the proposed method that we compare with the results of the classical model.
Physically-based enhancement in shallow water resimulation
Authors: Quan Hongyan , Song Yahui , Zhou Xinquan , Zhang Li
Published: June 2016

To resimulate a customized fluid derived product by analyzing an existing fluid is significant and difficult. This paper proposes a driven model recovery method, which is challenging in fluid resimulation customization. First, fluid physical properties are calculated under the constraints of appearance and dynamic behavior of the example water. Second, a hybrid particle lattice Boltzmann method for shallow water (LBMSW) is recovered from the dynamic geometry on fluid surface. As it is found that the resimulation details fade gradually with LBMSW auto-advection, a physically-based enhancement scheme is presented. A nonlinear algorithm is introduced to stretch the faded density to retain resimulation details. Experiments show that the proposed approach can obtain more realistic resimulation products in several challenging scenarios.
High-Frequency Trading Meets Online Learning
Authors: Fernandez-Tapia Joaquin
Published: June 2016

We propose an optimization framework for market-making in a limit order book, based on the theory of stochastic approximation. The idea is to take advantage of the iterative nature of the process of updating bid and ask quotes in order to make the algorithm optimize its strategy on a trial-and-error basis (i.e., online learning) using a variation of the stochastic gradient-descent algorithm. An advantage of this approach is that the exploration of the system by the algorithm is performed in run-time, so explicit specifications of price dynamics are not necessary, as is the case in the stochastic-control approach [(Gueant et al., 2013, Dealing with the Inventory Risk: A Solution to the Market Making Problem, Mathematics and Financial Economics 7(4), 477–507)]. For price/liquidity modeling, we consider a discrete-time variant of the Avellaneda–Stoikov model [(Avellaneda, M. and S. Stoikov, 2008, Liquidation in Limit Order Books with Controlled Intensity, Mathematical Finance 24(4), 627–650)] similar to its developent in the paper of Laruelle et al. [(Laruelle et al., 2013, Optimal Posting Price of Limit Orders: Learning by trading, Mathematics and Financial Economics 7(3), 359–403)] in the context of optimal liquidation tactics. Our aim is to set the ground for more advanced reinforcement learning techniques and to argue that the rationale of our method is generic enough to be extended to other classes of trading problems besides market-making.
Endovascular Embolization of an Aberrant Bronchial Artery Originating from the Internal Mammary Artery in a Patient with Hemoptysis
Authors: Fujii Hiroyuki , Fujita Akifumi , Nakamura Hiroyasu , Sasaki Takahiro , Sugimoto Hideharu
Published: June 2016

Massive hemoptysis is a life threatening respiratory emergency with high mortality and the bronchial artery (BA) is its most frequent source. Herein, we report a case of a 76-year-old man with recurrent hemoptysis due to an aberrant right BA arising from the right internal mammary artery (IMA), an extremely rare origin, that was clearly depicted on pretreatment computed tomography angiography (CTA). The patient was treated successfully by transcatheter bronchial artery embolization (BAE) of the aberrant BA and the hemoptysis has since been controlled for 9 months. Knowledge of the detailed BA anatomy is essential for performing BAE, especially in cases of aberrant BA. CTA is a promising tool for pretreatment planning of emergency BAE in patients with hemoptysis.
Highb-Value Diffusion MRI to Differentiate Recurrent Tumors from Posttreatment Changes in Head and Neck Squamous Cell Carcinoma: A Single Center Prospective Study
Authors: Acampora Angela , Manzo Gaetana , Fenza Giacomo , Busto Giuseppina , Serino Antonietta , Manto Andrea
Published: June 2016

Recently DW-MR Imaging has shown promising results in distinguishing between recurrent tumors and posttreatment changes in Head and Neck Squamous Cell Carcinoma (HNSSC). Aim of this study was to evaluate the diagnostic performances of DWI at highb-value (b= 2000 s/mm2) compared to standardb-value (b= 1000 s/mm2) andADCratiovalues (ADCratio=ADC2000/ADC1000×100) to differentiate recurrent tumors from posttreatment changes after treatment of HSNCC. 20 patients (16 M, 4 F) underwent MR Imaging between 2 and 16 months (mean 7) after treatment. Besides morphological sequences, we performed single-shot echo-planar DWI atb= 1000 s/mm2andb= 2000 s/mm2, and corresponding ADC maps were generated (ADC1000and ADC2000, resp.). By considering contrast-enhanced T1-weighted images as references, ROIs were drawn in order to evaluate mean ADC1000, ADC2000, andADCratio. The mean ADC1000and ADC2000in recurrent tumors were significantly lower than those in posttreatment changes (P=0.001andP=0.016, resp.). Moreover, the meanADCratiobetween the two groups showed a statistically significant difference (P=0.002). Sensitivity, specificity, and accuracy ofADCratiowere 82.0%, 100%, and 90%, respectively, by considering an optimal cutoff value of 65.5%.ADCratiois a promising value to differentiate between recurrent tumors and posttreatment changes in HNSCC and may be more useful than ADC1000and ADC2000.
Catastrophic Antiphospholipid Syndrome
Authors: El-Shereef Rawhya R. , El-Abedin Zein , Abdel Aziz Rashad , Talat Ibrahim , Saleh Mohammed , Abdel-Samia Hanna , Sameh Amro , Sharha Mahmoud
Published: June 2016

This paper reports one case of successfully treated patients suffering from a rare entity, the catastrophic antiphospholipid syndrome (CAPS). Management of this patient is discussed in detail.
Common Hepatic Duct Mixed Adenoneuroendocrine Carcinoma Masquerading as Cholangiocarcinoma
Authors: Priyanka Akhilesh Sali , Kamal Sunder Yadav , Chandralekha Tampi , Samir Parikh , Prasad Kashinath Wagle
Published: June 2016

Bile duct mixed adenoneuroendocrine carcinoma (MANEC) is a rare entity. It is defined as having mixed elements of both neuroendocrine tumors (NET) and an adenocarcinoma element, the lesser component forming at least 30% of the tumor. It is a subtype of neuroendocrine carcinoma (NEC) showing both gland-forming epithelial tumor cells and neuroendocrine cells. It is generally misdiagnosed as cholangiocarcinoma on imaging studies. The preoperative pathological workup from the endoscopic retrograde cholangiography brush cytology usually misses the NET/NEC component since it often lies deeper in the tumor. However, it is reported that it is the NEC component that defines the prognosis of the tumor; hence, it is vital to identify the NEC component. We present a rare case of common hepatic duct (CHD) MANEC that was preoperatively misdiagnosed as cholangiocarcinoma.
Supercritical Fluid Extract of Spent Coffee Grounds Attenuates Melanogenesis through Downregulation of the PKA, PI3K/Akt, and MAPK Signaling Pathways
Authors: Huang Huey-Chun , Wei Chien-Mei , Siao Jen-Hung , Tsai Tsang-Chi , Ko Wang-Ping , Chang Kuei-Jen , Hii Choon-Hoon , Chang Tsong-Min
Published: June 2016

The mode of action of spent coffee grounds supercritical fluid CO2 extract (SFE) in melanogenesis has never been reported. In the study, the spent coffee grounds were extracted by the supercritical fluid CO2 extraction method; the chemical constituents of the SFE were investigated by gas chromatography‐mass spectrometry (GC‐MS). The effects of the SFE and its major fatty acid components on melanogenesis were evaluated by mushroom tyrosinase activity assay and determination of intracellular tyrosinase activity and melanin content. The expression level of melanogenesis‐related proteins was analyzed by western blotting assay. The results revealed that the SFE of spent coffee grounds (1–10 mg/mL) and its major fatty acids such as linoleic acid and oleic acid (6.25–50 μM) effectively suppressed melanogenesis in the B16F10 murine melanoma cells. Furthermore, the SFE decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia‐associated transcription factor (MITF), tyrosinase, tyrosinase‐related protein‐1 (TRP‐1), and tyrosinase‐related protein‐2 (TRP‐2). The SFE also decreased the protein expression levels of p‐JNK, p‐p38, p‐ERK, and p‐CREB. Our results revealed that the SFE of spent coffee grounds attenuated melanogenesis in B16F10 cells by downregulation of protein kinase A (PKA), phosphatidylinositol‐3‐kinase (PI3K/Akt), and mitogen‐activated protein kinases (MAPK) signaling pathways, which may be due to linoleic acid and oleic acid.