bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Trial of Compression Duration After Transradial Cardiac Catheterization and Intervention
Authors: Lavi Shahar , Cheema Asim , Yadegari Andrew , Israeli Zeev , Levi Yaniv , Wall Sabrina , Alemayehu Mistre , Parviz Yasir , Murariu Bogdan‐Dorian , McPherson Terry , Syed Jaffer , Bagur Rodrigo 
Published: February 2017

Background

Radial artery occlusion is a known complication following transradial cardiac catheterization. A shorter duration of postprocedural radial clamp time may reduce radial artery occlusion (
RAO
) but might be associated with incomplete hemostasis.

Methods and Results

In total, 568 patients undergoing transradial diagnostic cardiac catheterization were randomly assigned to either 20 minutes (ultrashort) or 60 minutes (short) hemostatic compression time using patent hemostasis. Subsequently, clamp pressure was reduced gradually over 20 minutes. Access site hemostasis and
RAO
were assessed after clamp removal. Repeated assessment of
RAO
was determined at 1 week in 210 (37%) patients. Mean age was 64±11 years, and 30% were female. Percutaneous coronary intervention was performed in 161 patients.
RAO
immediately after clamp removal was documented in 14 (4.9%) and 8 (2.8%) patients in the 20‐ and 60‐minute clamp application groups, respectively (
P
=0.19). The incidence of grade 1 hematoma was higher in the 20‐minute group (6.7% versus 2.5%,
P
=0.015).
RAO
at 1 week after the procedure was 2.9% and 0.9% in the 20‐ and 60‐minute groups, respectively (
P
=0.36). Requirement for clamp retightening (36% versus 16%,
P
=0.01) was higher among patients who had
RAO
. Need for clamp retightening was the only independent predictor of
RAO
(
P
=0.04).

Conclusions

Ultrashort radial clamp application of 20 minutes is not preferable to a short duration of 60 minutes. The 60‐minute clamp duration is safe and provides good access site hemostasis with low
RAO
rates.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02269722.
‘The skies the limit!’
Authors: Fox Sarah Jane , Ismail Rosida 
Published: February 2017

Although legal practitioners recognise the terminology ‘open skies’ there is no one accepted definition. The principle aim maybe the same, namely ‘to democratise aviation’ but interpretation and practice translates through into variances and divisions as to how liberal nations are willing to be. This paper explores the concept and development of ‘open-skies’ with the intention of questioning whether this hypothesis is a realistic and an accomplishable objective.
This paper commences with a relevant-contextualised, historical exploration of open-skies agreements. The development of the us and eu are analysed before the research discusses the on-going developments in terms of the ‘potential’ of, and ‘difficulties’ in, realising asean-eu and asean-us open skies agreement.
The findings show the challenges and successes within the global aviation sector as viewed from this triangulated approach, and the conclusion drawn is that there remains impediments which will be difficult to overcome.
Myeloproliferative neoplasm stem cells
Authors: Mead Adam J. , Mullally Ann 
Published: February 2017

AbstractMyeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL. The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC.
Renal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy: analysis from a randomized placebo-controlled trial
Authors: Decloedt Eric H. , Lesosky Maia , Maartens Gary , Joska John A. 
Published: February 2017

Abstract
Background
The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination.

Objective
We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment.

Methods
We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo.

Results
We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks.

Conclusions
We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity.
Trial registration The study was registered on the Pan African Clinical Trials Registry (PACTR) with the identifier number PACTR201310000635418. Registered 11 October 2013 before the first participant was enrolled
Plug‐in‐Gait calculation of the knee adduction moment in people with knee osteoarthritis during shod walking: comparison of two different foot marker models
Authors: Paterson Kade L. , Hinman Rana S. , Metcalf Ben R. , Bennell Kim L. , Wrigley Tim V. 
Published: February 2017

AbstractBackgroundUnderstanding how kinematic multi‐segment foot modelling influences the utility of Plug‐in‐Gait calculations of the knee adduction moment (KAM) during shod walking is relevant to knee osteoarthritis (OA). Multi‐segment foot markers placed on the skin through windows cut in to the shoe provide a more accurate representation of foot mechanics than the traditional marker set used by Plug‐in‐Gait, which uses fewer markers, placed on the shoe itself. We aimed to investigate whether Plug‐in‐Gait calculation of the KAM differed when using a kinematic multi‐segment foot model compared to the traditional Plug‐in‐Gait marker set.MethodsTwenty people with medial knee OA underwent gait analysis in two test conditions: i) Plug‐in‐Gait model with its two standard foot markers placed on the shoes and; ii) Plug‐in‐Gait with the heel marker virtualised from a modified‐Oxford Foot Model where 8 ft markers were placed on the skin through windows cut in shoe uppers. Outcomes were the peak KAM, KAM impulse and other knee kinetic and kinematic variables.ResultsThere were no differences (P > 0.05) in any gait variables between conditions. Excellent agreement was found for all outcome variables, with high correlations (r > 0.88‐0.99, P < 0.001), narrow limits of agreement and no proportional bias (R2 = 0.03–0.14, P > 0.05). The mean difference and 95% confidence intervals for peak KAM were also within the minimal detectable change range demonstrating equivalence.ConclusionsPlug‐in‐Gait calculations of the KAM are not altered when using a kinematic multi‐segment foot marker model with skin markers placed through windows cut in to the shoe, instead of the traditional marker set placed on top of shoes. Researchers may be confident that applying either foot model does not change the calculation of the KAM using Plug‐in‐Gait.
Acute Kidney Injury in Patients Treated with Vancomycin and Piperacillin‐Tazobactam: A Retrospective Cohort Analysis
Authors: Rutter W. Cliff , Burgess Donna R. , Talbert Jeffery C. , Burgess David S. 
Published: February 2017

BACKGROUNDEmpiric antimicrobial therapy often consists of the combination of gram‐positive coverage with vancomycin (VAN) and gram‐negative coverage, specifically an antipseudomonal beta‐lactam such as piperacillin‐tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ.OBJECTIVEThis study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.DESIGN, SETTING, AND PATIENTSThis is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center.MEASUREMENTSThe primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End‐stage (RIFLE) criteria.METHODSContinuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed.RESULTSOverall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, P < 0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI], 1.74‐2.39; aOR, 2.31; 95% CI, 1.97‐2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function.CONCLUSIONSIn this study of more than 10,000 patients, VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy.
Protective effect of cinnamon against cadmium-induced hepatorenal oxidative damage in rats
Authors: Abdeen Ahmed , Ghonim Ahmed , El-Shawarby Ragab , Abdel-Aleem Nabila , El-Shewy Elham , Abdo Mohamed , Abdelhiee Ehab 
Published: February 2017

Background: Cadmium (Cd) is a well-known hazardous environmental contaminant. It exerts its toxicity through induction of lipid peroxidation and reduction of cellular antioxidant. Therefore, in this study, we investigated whether cinnamon could protect against Cd toxicity in liver and kidney.Materials and methods: Forty male Wister rats (130-135 gm) were divided randomly into 4 groups/ 10 rats each. Control, cinnamon, cadmium, and Cinn+Cd groups received distilled water, cinnamon extract (200 mg/kg b.wt. orally), cadmium chloride (5 mg/kg b.wt. orally), and Cd plus cinnamon, respectively. Blood, liver, and kidney samples were collected after 8 weeks of treatment. Erythrogram, leukogram, liver and kidney functions, and oxidative status (MDA, CAT, and TAC) were determined.Results and discussion: Cd-treated animals showed significant increases in serum ALT, AST, creatinine, and urea indicating hepatic and renal damage. Cd-induced oxidative stress was observed by marked decease TAC accompanied by increase in MDA which contributed in liver and kidney dysfunction. Co-treatment of Cd with cinnamon has improved the oxidation profile by increasing the TAC and decreasing the lipid peroxidation. Cinnamon ameliorated the toxic effect of Cd, which observed by improvement of liver and kidney functions.Conclusion:Â High antioxidants content of cinnamon could protect the liver and kidney from Cd toxicity.Â
Hypercontractivity, supercontractivity, ultraboundedness and stability in semilinear problems
Authors: Addona Davide , Angiuli Luciana , Lorenzi Luca 
Published: February 2017

Abstract
We study the Cauchy problem associated to a family of nonautonomous semilinear equations in the space of bounded and continuous functions over

ℝ
d

{\mathbb{R}^{d}}

and in

L
p

{L^{p}}

-spaces with respect to tight evolution systems of measures. Here, the linear part of the equation is a nonautonomous second-order elliptic operator with unbounded coefficients defined in

I
×

ℝ
d

{I\times\mathbb{R}^{d}}

, (I being a right-halfline).
To the above Cauchy problem we associate a nonlinear evolution operator, which we study in detail, proving some summability improving properties. We also study the stability
of the null solution to the Cauchy problem.
Accuracy of cerebrospinal fluid Aβ1-42 measurements: evaluation of pre-analytical factors using a novel Elecsys immunosassay
Authors: Rozga Malgorzata , Bittner Tobias , Höglund Kina , Blennow Kaj 
Published: February 2017

AbstractBackground:A decreased level of Aβ1-42 in cerebrospinal fluid (CSF) is characteristic of Alzheimer disease and often used to support clinical diagnosis. The measured concentration of CSF Aβ1-42, however, depends strongly on several pre-analytical and analytical “confounding” factors such as sample collection, material of testing tube, CSF handling and storage procedures (e.g. transfer to new tubes after centrifugation, freeze-thaw effects). As a consequence, substantial variations in the measured levels of this biomarker are observed even for the same sample. This study investigates whether the accuracy of quantitative analysis of CSF Aβ1-42 can be improved by pre-analytical treatment of CSF with agents that could potentially reduce a freeze-thaw and adhesion-related depletion of Aβ1-42 from CSF, including modulators of Aβ aggregation and cryoprotecting or anti-adhesion agents.Methods:The concentration of CSF Aβ1-42 was assessed with a novel Elecsys immunoassay developed for quantification of Aβ1-42 in human CSF.Results:Low-molecular weight Aβ oligomerization inhibitors, β-sheet breaker peptides, or the mid domain 4G8 antibody do not improve the stability of CSF Aβ1-42 during a repeated freeze-thaw treatment. Cryoprotecting agents reduce a freeze-thaw dependent loss of Aβ1-42 only when spiked to CSF to final concentration of 300 mM or higher. Adhesion of Aβ1-42 can be prevented by pre-treating CSF with Tween or by using tubes with a siliconized surface.Conclusions:Between-center variability in measured level of CSF Aβ1-42 can be reduced only by standardized CSF collection into one specific tube that, without centrifugation, transfer or other types of pre-analytical processing, is directly analyzed after sample collection.
Temperature Manipulation in Songbird Brain Implicates the Premotor Nucleus HVC in Birdsong Syntax
Authors: Zhang Yisi S. , Wittenbach Jason D. , Jin Dezhe Z. , Kozhevnikov Alexay A. 
Published: February 2017

Variable motor sequences of animals are often structured and can be described by probabilistic transition rules between action elements. Examples include the songs of many songbird species such as the Bengalese finch, which consist of stereotypical syllables sequenced according to probabilistic rules (song syntax). The neural mechanisms behind such rules are poorly understood. Here, we investigate where the song syntax is encoded in the brain of the Bengalese finch by rapidly and reversibly manipulating the temperature in the song production pathway. Cooling the premotor nucleus HVC (proper name) slows down the song tempo, consistent with the idea that HVC controls moment-to-moment timings of acoustic features in the syllables. More importantly, cooling HVC alters the transition probabilities between syllables. Cooling HVC reduces the number of repetitions of long-repeated syllables and increases the randomness of syllable sequences. In contrast, cooling the downstream motor area RA (robust nucleus of the acropallium), which is critical for singing, does not affect the song syntax. Unilateral cooling of HVC shows that control of syllables is mostly lateralized to the left HVC, whereas transition probabilities between the syllables can be affected by cooling HVC in either hemisphere to varying degrees. These results show that HVC is a key site for encoding song syntax in the Bengalese finch. HVC is thus involved both in encoding timings within syllables and in sequencing probabilistic transitions between syllables. Our finding suggests that probabilistic selections and fine-grained timings of action elements can be integrated within the same neural circuits.SIGNIFICANCE STATEMENTMany animal behaviors such as birdsong consist of variable sequences of discrete actions. Where and how the probabilistic rules of such sequences are encoded in the brain is poorly understood. We locally and reversibly cooled brain areas in songbirds during singing. Mild cooling of area HVC in the Bengalese finch brain—a premotor area homologous to the mammalian premotor cortex—alters the statistics of the syllable sequences, suggesting that HVC is critical for birdsong sequences. HVC is also known for controlling moment-to-moment timings within syllables. Our results show that timing and probabilistic sequencing of actions can share the same neural circuits in local brain areas.
A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans
Authors: Koch Evan , Novembre John 
Published: February 2017

AbstractWhen mutations have small effects on fitness, population size plays an important role in determining the amount and nature of deleterious genetic variation. The extent to which recent population size changes have impacted deleterious variation in humans has been a question of considerable interest and debate. An emerging consensus is that the Out-of-Africa bottleneck and subsequent growth events have been too short to cause meaningful differences in genetic load between populations; though changes in the number and average frequencies of deleterious variants have taken place. To provide more support for this view and to offer additional insight into the divergent evolution of deleterious variation across populations, we numerically solve time-inhomogeneous diffusion equations and study the temporal dynamics of the frequency spectra in models of population size change for modern humans. We observe how the response to demographic change differs by the strength of selection, and we then assess whether similar patterns are observed in exome sequence data from 33,370 and 5203 individuals of non-Finnish European and West African ancestry, respectively. Our theoretical results highlight how even simple summaries of the frequency spectrum can have complex responses to demographic change. These results support the finding that some apparent discrepancies between previous results have been driven by the behaviors of the precise summaries of deleterious variation. Further, our empirical results make clear the difficulty of inferring slight differences in frequency spectra using recent next-generation sequence data.
Comparative Transcriptomics of Malaria Mosquito Testes: Function, Evolution, and Linkage
Authors: Cassone Bryan J , Kay Raissa G G , Daugherty Matthew P , White Bradley J 
Published: February 2017

AbstractTestes-biased genes evolve rapidly and are important in the establishment, solidification, and maintenance of reproductive isolation between incipient species. The Anopheles gambiae complex, a group of at least eight isomorphic mosquito species endemic to Sub-Saharan Africa, is an excellent system to explore the evolution of testes-biased genes. Within this group, the testes are an important tissue in the diversification process because hybridization between species results in sterile hybrid males, but fully fertile females. We conducted RNA sequencing of A. gambiae and A. merus carcass and testes to explore tissue- and species-specific patterns of gene expression. Our data provides support for transcriptional repression of X-linked genes in the male germline, which likely drives demasculinization of the X chromosome. Testes-biased genes predominately function in cellular differentiation and show a number of interesting patterns indicative of their rapid evolution, including elevated dN/dS values, low evolutionary conservation, poor annotation in existing reference genomes, and a high likelihood of differential expression between species.
Requirements for Driving Antipathogen Effector Genes into Populations of Disease Vectors by Homing
Authors: Beaghton Andrea , Hammond Andrew , Nolan Tony , Crisanti Andrea , Godfray H Charles J , Burt Austin 
Published: February 2017

AbstractThere is a need for new interventions against the ongoing burden of vector-borne diseases such as malaria and dengue. One suggestion has been to develop genes encoding effector molecules that block parasite development within the vector, and then use the nuclease-based homing reaction as a form of gene drive to spread those genes through target populations. If the effector gene reduces the fitness of the mosquito and does not contribute to the drive, then loss-of-function mutations in the effector will eventually replace functional copies, but protection may nonetheless persist sufficiently long to provide a public health benefit. Here, we present a quantitative model allowing one to predict the duration of protection as a function of the probabilities of different molecular processes during the homing reaction, various fitness effects, and the efficacy of the effector in blocking transmission. Factors that increase the duration of protection include reducing the frequency of pre-existing resistant alleles, the probability of nonrecombinational DNA repair, the probability of homing-associated loss of the effector, the fitness costs of the nuclease and effector, and the completeness of parasite blocking. For target species that extend over an area much larger than the typical dispersal distance, the duration of protection is expected to be highest at the release site, and decrease away from there, eventually falling to zero, as effector-less drive constructs replace effector-containing ones. We also model an alternative strategy of using the nuclease to target an essential gene, and then linking the effector to a sequence that restores the essential function and is resistant to the nuclease. Depending upon parameter values, this approach can prolong the duration of protection. Our models highlight the key design criteria needed to achieve a desired level of public health benefit.