bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and pharmacokinetics of salmeterol in thoroughbred horses following inhaled administration
Authors: Fenwick S. J. , Hincks P. R. , Scarth J. P. , Wieder M. E. , Hillyer L. L. , Paine S. W. 
Published: January 2017

Salmeterol is a man‐made beta‐2‐adrenergic receptor agonist used to relieve bronchospasm associated with inflammatory airway disease in horses. Whilst judicious use is appropriate in horses in training, they cannot race with clinically effective concentrations of medications under the British Horseracing Authority's Rules of Racing. Salmeterol must therefore be withdrawn prior to race day and pharmacokinetic (PK) studies used to establish formal detection time advice. Salmeterol xinafoate (Serevent Evohaler®) was administered (0.1 mg twice daily for 4.5 days) via inhalation to six horses. Urine and blood samples were taken up to 103 h postadministration. Hydrolysed samples were extracted using solid phase extraction. A sensitive Ultra high performance tandem mass spectrometry (UPLC‐MS/MS) method was developed, with a Lower limit of quantification (LLOQ) for salmeterol of 10 pg/mL in both matrices. The majority of salmeterol plasma concentrations, postlast administration, were below the method LLOQ and so unusable for PK analysis. Urine PK analysis suggested a half‐life consistent with duration of pharmacological effect. Average estimated urine concentration at steady‐state was obtained via PK modelling and used to estimate a urine concentration of 59 ± 34 pg/mL as a marker of effective lung concentration. From this, potential detection times were calculated using a range of safety factors.
Pharmacokinetics and selected pharmacodynamics of romifidine following low‐dose intravenous administration in combination with exercise to quarter horses
Authors: Knych H. K. , Stanley S. D. , McKemie D. S. , Steinmetz S. J. 
Published: January 2017

Romifidine is an alpha‐2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low‐dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography–tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhythm following intravenous administration of romifidine followed by exercise. Eight adult Quarter Horses received a single intravenous dose of 5 mg (0.01 mg/kg) romifidine followed by 1 h of exercise. Blood samples were collected and drug concentrations measured at time 0 and at various times up to 72 h. Mean ± SD systemic clearance, steady‐state volume of distribution and terminal elimination half‐life were 34.1 ± 6.06 mL/min/kg and 4.89 ± 1.31 L/kg and 3.09 ± 1.18 h, respectively. Romifidine serum concentrations fell below the LOQ (0.01 ng/mL) and the LOD (0.005 ng/mL) by 24 h postadministration. Heart rate and rhythm appeared unaffected when a low dose of romifidine was administered immediately prior to exercise.
A national research and development blueprint for sustainable lake basin management in Malaysia
Authors: Sharip Zati , Suratman Saim , Shaaban Ahmad J. 
Published: January 2017

AbstractThe deterioration of water quality in lakes resulting from unsustainable catchment practices requires concerted efforts to address them, in the form of cooperation among government agencies and institutions, private bodies and the community‐at‐large. Research that provides an understanding of a lake's ecosystem is an important aspect of making informed decisions for sustainable management and governance of lakes. The present study describes the findings of literature reviews on Malaysian lakes, and the national efforts made to establish an agenda for lake research and development in Malaysia directed towards integrated lake basin management (ILBM). The main findings and outcomes of the National Lake Research Blueprint workshop in April 2014 on the issues facing lakes and reservoirs are highlighted. Seven research themes were identified, namely (i) ecosystem services and socio‐economic development, (ii) governance, (iii) water quality and pollution, (iv) eco‐hydrology and basin management, (v) biodiversity and natural products, (vi) physical limnology and hydrodynamics and (vii) technology. The goal is to enhance research and development on sustainable lake basin management directed to conservation and development targets. The findings of this study provide an integrated research framework that can support ILBM governance elements (pillars) elsewhere, and to call for researchers to participate in much‐needed research areas.
Impacts of dam construction on streamflows during drought periods in the Upper Colorado River Basin, Texas
Authors: Mix Ken , Groeger Alan W. , Lopes Vicente L. 
Published: January 2017

AbstractThe purpose of this study was to assess the impacts of dam construction on streamflow during a severe drought in the upper Colorado River basin (TX), upstream of Lake Buchanan reservoir. The region has experienced severe, prolonged droughts over the past century. To ameliorate the effects of drought, and increase water storage for use during dry periods, several dams were constructed on the mainstem and tributaries of the Colorado River upstream of Lake Buchanan since the late‐1940s. Analysis of flow at the gauge above Lake Buchanan indicated streamflow was significantly reduced during the recent drought (2009–2014), compared with streamflows during the ‘drought of record’ (1950–1957). The construction of these upstream dams reduced streamflow by intercepting and storing water. It is concluded that building reservoirs in the western portion of the basin, largely in response to past droughts, although increasing water supplies for local uses, exacerbated the downstream effects of the hydrological drought, essentially making it the worst in recorded history.
Natural history of nonimmune‐mediated thrombocytopenia and acute kidney injury in pediatric open‐heart surgery
Authors: Tew Shannon , Fontes Manuel L. , Greene Nathaniel H. , Kertai Miklos D. , Ofori‐Amanfo George , Jaquiss Robert D. B. , Lodge Andrew J. , Ames Warwick A. , Homi Hercilia Mayumi , Machovec Kelly A. , Jooste Edmund H. 
Published: January 2017

SummaryObjectiveThrombocytopenia and acute kidney injury (AKI) are common following pediatric cardiac surgery with cardiopulmonary bypass (CPB). However, the relationship between postoperative nadir platelet counts and AKI has not been investigated in the pediatric population. Our objective was to investigate this relationship and examine independent predictors of AKI.DesignAfter IRB approval, we performed a retrospective review of the institution's medical records and database. Setting: This study was performed at a single institution over a 5‐year period. Patients: We included patients <21 years of age undergoing cardiac surgery with CPB. Interventions: Demographics, laboratory, and surgical characteristics were captured, and clinical event rates were recorded. Measurements: Descriptive statistics were used to evaluate platelet and creatinine distributions. T‐tests and chi‐squared tests were used to compare characteristics among Acute Kidney Injury Network groups. Multivariable logistic and ordinal logistic regression models were used to determine the association of our predictor of interest, postoperative nadir platelet count and AKI.ResultsEight hundred and fourteen patients (23% infants and 23% neonates) were included in the analysis. Postoperative platelet counts decreased 48% from baseline reaching a mean nadir value of 150 × 109·l−1 on postoperative day 3. AKI occurred in 37% of patients including 13%, 17%, and 6% with Acute Kidney Injury Network stages 1, 2, and 3, respectively. The magnitude of nadir platelet counts correlated with the severity of AKI. Independent predictors of severity of AKI include nadir platelet counts, CPB time, Aristotle score, patient weight, intra‐operative packed red blood cell transfusion, and having a heart transplant procedure.ConclusionsIn pediatric open‐heart surgery, thrombocytopenia and AKI occur commonly following CPB. Our findings show a strong association between nadir platelet counts and the severity of AKI.
Down‐regulation of BnDA1, whose gene locus is associated with the seeds weight, improves the seeds weight and organ size in Brassica napus
Authors: Wang Jie‐Li , Tang Min‐Qiang , Chen Sheng , Zheng Xiang‐Feng , Mo Hui‐Xian , Li Sheng‐Jun , Wang Zheng , Zhu Ke‐Ming , Ding Li‐Na , Liu Sheng‐Yi , Li Yun‐Hai , Tan Xiao‐Li 
Published: January 2017

SummaryBrassica napus L. is an important oil crop worldwide and is the main raw material for biofuel. Seed weight and seed size are the main contributors to seed yield. DA1 (DA means big in Chinese) is an ubiquitin receptor and negatively regulates seed size. Down‐regulation of AtDA1 in Arabidopsis leads to larger seeds and organs by increasing cell proliferation in integuments. In this study, BnDA1 was down‐regulated in B. napus by over expressed of AtDA1R358K, which is a functional deficiency of DA1 with an arginine‐to‐lysine mutation at the 358th amino acid. The results showed that the biomass and size of the seeds, cotyledons, leaves, flowers and siliques of transgenic plants all increased significantly. In particular, the 1000 seed weight increased 21.23% and the seed yield per plant increased 13.22% in field condition. The transgenic plants had no negative traits related to yield. The candidate gene association analysis demonstrated that the BnDA1 locus was contributed to the seeds weight. Therefore, our study showed that regulation of DA1 in B. napus can increase the seed yield and biomass, and DA1 is a promising target for crop improvement.
Synthetic lethality: emerging targets and opportunities in melanoma
Authors: Thompson Nicola , Adams David J. , Ranzani Marco 
Published: January 2017

SummaryGreat progress has been made in the treatment of melanoma through use of targeted therapies and immunotherapy. One approach that has not been fully explored is synthetic lethality, which exploits somatically acquired changes, usually driver mutations, to specifically kill tumour cells. We outline the various approaches that may be applied to identify synthetic lethal interactions and define how these interactions may drive drug discovery efforts.
High neutrophil : lymphocyte ratio is associated with refractory Kawasaki disease
Authors: Cho Hong‐Je , Bak So Young , Kim Su Yeong , Yoo Rita , Baek Hae‐Sung , Yang Seung , Hwang Il‐Tae , Ban Ji‐Eun 
Published: January 2017

AbstractBackgroundThe clinical significance of the neutrophil : lymphocyte ratio (NLR) has not yet been fully elucidated in Kawasaki disease (KD). The purpose of this study was to investigate the relationship between NLR and response to i.v. immunoglobulin (IVIG), and its effect on coronary abnormalities in KD.MethodsA total of 196 KD patients treated with IVIG were analyzed. Baseline NLR was evaluated immediately before IVIG therapy and the patients classified into two groups according to NLR. The clinical data, other inflammatory biomarkers, and coronary complications were also assessed.ResultsKawasaki disease patients with NLR ≥ 5 had a greater incidence of IVIG refractoriness than the NLR < 5 group (31.7% vs 4.3%, P < 0.001), but this was not related to the development of coronary abnormalities. The change in NLR after IVIG (i.e. ΔNLR) was significantly decreased in the coronary abnormality group (2.65 ± 1.88 vs 3.81 ± 2.55, P = 0.042). On multivariate analysis, high NLR and CRP were independent predictors of IVIG refractoriness during the acute phase of KD (P = 0.032 in NLR; P = 0.029 in CRP, respectively).ConclusionsHigh NLR was closely associated with resistance to IVIG, but it was not related to the occurrence of coronary abnormalities in KD. Low ΔNLR after IVIG, however, was significantly associated with coronary artery abnormalities.
Tidal marsh restoration stimulates the growth of winter shorebird populations in a temperate estuary
Authors: Kelly John P. , Condeso T. Emiko 
Published: January 2017

AbstractThe regional responses of winter shorebird populations in the nearly 3,000 ha estuary of Tomales Bay, California, to the restoration of 223 ha of historic tidal wetlands were evaluated for 27 years: 19 years prior to tidal reintroduction and 8 years after tidal reintroduction. We used interrupted time series analyses to measure the spatial extent of the restoration effect and to model the magnitude and length of time associated with the gradual, restoration‐induced growth of winter shorebird populations in the bay. Expanded, regional benefits of the restoration were revealed by consistent patterns of winter shorebird population growth. Eight years after tidal reintroduction, overall shorebird abundances in southern Tomales Bay nearly tripled in response to the restoration. Substantial winter population growth by most species in southern Tomales Bay was evident within 3 years after tidal reintroduction, and maximum responses to the restoration were estimated to be predominantly achieved within 8 years. In contrast to strong effects of tidal marsh restoration on winter shorebird populations in southern Tomales Bay, no significant overall responses were exhibited by shorebirds in the northern portion of the bay, although marginal evidence of expanded effects on a few species in northern Tomales Bay were suggested. The results illustrate the importance of accounting for restoration effects beyond the spatial and temporal boundaries of the restored habitat, to consider both the potentially expanded benefits and the spatial limits of those benefits to regional wildlife populations.
Revisiting the Narrative Approach of Estimating Tax Multipliers
Authors: Hebous Shafik , Zimmermann Tom 
Published: January 2017

AbstractWe analyze whether popular measures of narrative tax shocks can be treated as relevant instruments for observable endogenous tax series of interest. We find that narrative tax measures are only weakly correlated with cyclically adjusted tax revenues for the US and the UK. Using weak‐instrument robust inference, narrative tax measures often yield insignificant estimates of tax multipliers. We conclude that the literature currently understates the uncertainty associated with estimating the tax multiplier using the narrative approach.
Wealth, Wages, and Wedlock: Explaining the College Gender Gap Reversal
Authors: Reijnders Laurie S. M. 
Published: January 2017

AbstractIn this paper, I study the role of changes in the wage structure and expectations about marriage in explaining the college gender gap reversal. With strongly diminishing marginal utility of wealth and in the presence of a gender wage gap, single women have a greater incentive than single men to invest in education. Marriage‐market distortions tend to depress the overall benefit of education for women relative to men. I develop a tractable two‐period model and parameterize it using US census data for the cohort born in 1950. I then show that it can generate a reversal and that the most important driving force for this is the decline in marriage rates.
Competitive traits of the invasive grass Arundo donax are enhanced by carbon dioxide and nitrogen enrichment
Authors: Nackley L , Hough‐Snee N , Kim S‐H 
Published: January 2017

SummaryIncreased atmospheric carbon dioxide (CO2) and soil nitrogen (N) may confer competitive advantages to invasive species over native plant species. We conducted a two‐way factorial experiment, growing the model invasive plant Arundo donax in CO2 growth chambers to test how CO2 and N availability interact to affect plant growth and biomass allocation. CO2 was supplied at c. 400 mg L−1 and c. 750 mg L−1. N was supplied as ammonium nitrate at 640, 320 and 80 mg L−1. We hypothesised that the fertilisation effect of CO2 enrichment would offset limitations from N deficiency. The results indicated that A. donax plants grown with enriched CO2 and abundant N accumulated approximately 50–100% more biomass and allocated approximately 50% more biomass to rhizomes than plants grown under ambient CO2 conditions. Neither treatment affected the leaf area per unit mass (specific leaf area; SLA). Greater growth will likely increase A. donax's competitive potential, because increased rhizome biomass has been associated with increased stress tolerance and post‐disturbance resprouting capacity. The consistent SLA under all treatments suggests that A. donax has a morphological strategy that prioritises increasing leaf quantity over increasing individual leaves' photosynthetic potential. These results reveal the ecological strategies that contribute to the successful establishment, dominance and persistence of this invasive plant species.
Influence of
rhlR
and
lasR
on Polymyxin Pharmacodynamics in Pseudomonas aeruginosa and Implications for Quorum Sensing Inhibition with Azithromycin
Authors: Bulman Zackery P. , Ly Neang S. , Lenhard Justin R. , Holden Patricia N. , Bulitta Jürgen B. , Tsuji Brian T. 
Published: January 2017

ABSTRACT

The impact of quorum sensing on polymyxin and azithromycin pharmacodynamics was assessed in
Pseudomonas aeruginosa
PAO1 and an isogenic
rhlR
/
lasR
double knockout. For polymyxin B, greater killing against the
rhlR
/
lasR
knockout than against PAO1 was observed at 10
8
CFU/ml (polymyxin B half-maximal effective concentration [EC
50
], 5.61 versus 12.5 mg/liter, respectively;
P
< 0.005). Polymyxin B combined with azithromycin (256 mg/liter) was synergistic against each strain, significantly reducing the respective polymyxin B EC
50
compared to those with monotherapy (
P
< 0.005), and is a promising strategy by which to combat
P. aeruginosa
.
Impact of Extended Duration of Artesunate Treatment on Parasitological Outcome in a Cytocidal Murine Malaria Model
Authors: Walker Leah A. , Sullivan David J. 
Published: January 2017

ABSTRACT

Artemisinin-based combination therapies are a key pillar in global malaria control and are recommended as a first-line
Plasmodium falciparum
treatment. They rely upon a rapid 4-log-unit reduction in parasitemia by artemisinin compounds with a short half-life and the killing of remaining parasites by a partner compound with a longer half-life. Current treatment guidelines stipulate giving three 24-h-interval doses or six 12-h-interval doses over a 3-day period. Due to the short half-life of artesunate and artemether, almost all of the resulting cytocidal activity is confined within a single 48-h asexual
P. falciparum
cycle. Here, we utilized a luciferase reporter,
Plasmodium berghei
ANKA, in a cytocidal model in which treatment was initiated at high parasitemia, allowing us to monitor a greater than 3-log-unit reduction in parasite density, as well as 30-day survival. In this study, we demonstrated that increasing the artesunate duration from spanning one asexual cycle to spanning three asexual cycles while keeping the total dose constant results in enhanced cytocidal activity. Single daily artesunate doses at 50 mg/kg of body weight over 7 days were the minimum necessary for curative monotherapy. In combination with a single sub-human-equivalent dose of the partner drug amodiaquine or piperaquine, the three-asexual-cycle artesunate duration was able to cure 75% and 100% of mice, respectively, whereas 0% and 33% cures were achieved with the single-asexual-cycle artesunate duration. In summary, cytocidal activity of the artemisinin compounds, such as artesunate, can be improved solely by altering the dosing duration.
In Vitro
Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis
Authors: Grohs Patrick , Taieb Gary , Morand Philippe , Kaibi Iheb , Podglajen Isabelle , Lavollay Marie , Mainardi Jean-Luc , Compain Fabrice 
Published: January 2017

ABSTRACT

Ceftolozane-tazobactam was tested against 58 multidrug-resistant nonfermenting Gram-negative bacilli (35
Pseudomonas aeruginosa
, 11
Achromobacter xylosoxydans
, and 12
Stenotrophomonas maltophilia
isolates) isolated from cystic fibrosis patients and was compared to ceftolozane alone, ceftazidime, meropenem, and piperacillin-tazobactam. Ceftolozane-tazobactam was the most active agent against
P. aeruginosa
but was inactive against
A. xylosoxydans
and
S. maltophilia
. In time-kill experiments, ceftolozane-tazobactam had complete bactericidal activity against 2/6 clinical isolates (33%).
Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection
Authors: Wren John T. , Blevins Lance K. , Pang Bing , Basu Roy Ankita , Oliver Melissa B. , Reimche Jennifer L. , Wozniak Jessie E. , Alexander-Miller Martha A. , Swords W. Edward 
Published: January 2017

ABSTRACT

Even in the vaccine era,
Streptococcus pneumoniae
(the pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large part because of the high prevalence of nasal colonization with the pneumococcus in children. The primary pneumococcal neuraminidase, NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease by
S. pneumoniae
, in part via the synergistic contributions of the viral neuraminidase. The specific role of its pneumococcal counterpart, NanA, in this interaction, however, is less well understood. We demonstrate in a mouse model that NanA-deficient pneumococci are impaired in their ability to cause both nasal colonization and middle ear infection. Coinfection with neuraminidase-expressing influenza virus and
S. pneumoniae
potentiates both colonization and infection but not to wild-type levels, suggesting an intrinsic role of NanA. Using
in vitro
models, we show that while NanA contributes to both epithelial adherence and biofilm viability, its effect on the latter is actually independent of its sialidase activity. These data indicate that NanA contributes both enzymatically and nonenzymatically to pneumococcal pathogenesis and, as such, suggest that it is not a redundant bystander during coinfection with influenza A virus. Rather, its expression is required for the full synergism between these two pathogens.