bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug treatment of macular oedema secondary to central retinal vein occlusion: a network meta-analysis
Authors: Ford John A , Shyangdan Deepson , Uthman Olalekan A , Lois Noemi , Waugh Norman
Published: July 2014

Objective

To indirectly compare aflibercept, bevacizumab, dexamethasone, ranibizumab and triamcinolone for treatment of macular oedema secondary to central retinal vein occlusion using a network meta-analysis (NMA).

Design

NMA.

Data sources

The following databases were searched from January 2005 to March 2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL; Science Citation Index and Conference Proceedings Citation Index-Science.

Eligibility criteria for selecting studies

Only randomised controlled trials assessing patients with macular oedema secondary to central retinal vein occlusion were included. Studies had to report either proportions of patients gaining ≥3 lines, losing ≥3 lines, or the mean change in best corrected visual acuity. Two authors screened titles and abstracts, extracted data and undertook risk of bias assessment. Bayesian NMA was used to compare the different interventions.

Results

Seven studies, assessing five drugs, were judged to be sufficiently comparable for inclusion in the NMA. For the proportions of patients gaining ≥3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of being more effective than sham and dexamethasone. A smaller proportion of patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg or aflibercept 2 mg lost ≥3 lines of vision compared to those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of improvement in the mean best corrected visual acuity compared to those treated with sham injections.

Conclusions

We found no evidence of differences between ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The antivascular endothelial growth factors (VEGFs) are likely to be favoured because they are not associated with steroid-induced cataract formation. Aflibercept may be preferred by clinicians because it might require fewer injections.

Systematic review registration

Not registered.
The first 1000 days of life: prenatal and postnatal risk factors for morbidity and growth in a birth cohort in southern India
Authors: Kattula Deepthi , Sarkar Rajiv , Sivarathinaswamy Prabhu , Velusamy Vasanthakumar , Venugopal Srinivasan , Naumova Elena N , Muliyil Jayaprakash , Ward Honorine , Kang Gagandeep
Published: July 2014

Objective

To estimate the burden and assess prenatal and postnatal determinants of illnesses experienced by children residing in a semiurban slum, during the first 1000 days of life.

Design

Community-based birth cohort

Setting

Southern India

Participants

Four hundred and ninety-seven children of 561 pregnant women recruited and followed for 2 years with surveillance and anthropometry.

Main outcome measure

Incidence rates of illness; rates of clinic visits and hospitalisations; factors associated with low birth weight, various illnesses and growth.

Results

Data on 10 377.7 child-months of follow-up estimated an average rate of 14.8 illnesses/child-year. Gastrointestinal and respiratory illnesses were 20.6% and 47.8% of the total disease burden, respectively. The hospitalisation rate reduced from 46/100 child-years during infancy to 19/100 child-years in the second year. Anaemia during pregnancy (OR=2.3, 95% CI=1.08 to 5.18), less than four antenatal visits (OR=6.8, 95% CI=2.1 to 22.5) and preterm birth (OR=3.3, 95% CI=1.1 to 9.7) were independent prenatal risk factors for low birth weight. Female gender (HR=0.88, 95% CI=0.79 to 0.99) and 6 months of exclusive breast feeding (HR=0.76, 95% CI=0.66 to 0.88) offered protection against all morbidity. Average monthly height and weight gain were lower in female child and children exclusively breast fed for 6 months.

Conclusions

The high morbidity in Indian slum children in the first 1000 days of life was mainly due to prenatal factors and gastrointestinal and respiratory illness. Policymakers need disease prevalence and pathways to target high-risk groups with appropriate interventions in the community.
Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)
Authors: Quint Jennifer K , Müllerova Hana , DiSantostefano Rachael L , Forbes Harriet , Eaton Susan , Hurst John R , Davis Kourtney , Smeeth Liam
Published: July 2014

Objectives

The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.

Setting

951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.

Primary outcome measure

The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.

Results

951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5–92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7–94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2–44.4%).

Conclusions

Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004.
RAndomised controlled trial to imProve depressIon and the quality of life of people with Dementia using cognitive bias modification: RAPID study protocol
Authors: Almeida Osvaldo P , MacLeod Colin , Flicker Leon , Ford Andrew , Grafton Ben , Etherton-Beer Christopher
Published: July 2014

Introduction

Depressive symptoms are common and undermine the quality of life of people with Alzheimer's disease (AD). Cholinesterase inhibitors and antidepressants have all but no effect on the mood of patients, and their use increases adverse events. Cognitive bias modification (CBM) targets attentional and interpretative biases associated with anxiety, dysphoria and depression and may be useful to treat depression in AD (DAD). This trial aims to determine the effect of CBM on depression scores and the quality of life of people with DAD.

Methods and analysis

Randomised, double-blind, parallel, controlled trial of CBM (1:1 allocation ratio). Participants will be 80 adults with probable AD living in the Western Australian community who score 8 or more on the Cornell Scale for Depression in Dementia (CSDD). They will have mild to moderate dementia (Mini-Mental State Examination—MMSE score ≥15) and will be free of severe sensory impairment or suicidal intent. The intervention will consist of 10 40 min sessions of CBM delivered over 2 weeks using a high-resolution monitor using a local computer station at the Western Australian Centre for Health and Ageing. The primary outcomes of interest are the 2-week change, from baseline, in the severity of CSDD scores and the Quality of Life AD (QoL-AD) scores. Secondary outcomes include changes in the CSDD, QoL-AD after 12 weeks, and changes in MMSE scores, negative attentional and interpretative bias and the proportion of participants with CSDD <8 after 2 and 12 weeks.

Ethics and dissemination

The study will comply with the principles of the Declaration of Helsinki and participants will provide written informed consent. The Ethics Committee of the Royal Perth Hospital will approve and oversee the study (REG14-036). The results of this trial will provide level 2 evidence of efficacy for CBM as a treatment of DAD.

Trial registration number

Australian and New Zealand Clinical Trials Registry number ACTRN12614000420640, date registered 06/04/2014.
Estimating population prevalence of potential airflow obstruction using different spirometric criteria: a pooled cross-sectional analysis of persons aged 40–95 years in England and Wales
Authors: Scholes Shaun , Moody Alison , Mindell Jennifer S
Published: July 2014

Objectives

Consistent estimation of the burden of chronic obstructive pulmonary disease (COPD) has been hindered by differences in methods, including different spirometric cut-offs for impaired lung function. The impact of different definitions on the prevalence of potential airflow obstruction, and its associations with key risk factors, is evaluated using cross-sectional data from two nationally representative population surveys.

Design

Pooled cross-sectional analysis of Wave 2 of the UK Household Longitudinal Survey and the Health Survey for England 2010, including 7879 participants, aged 40–95 years, who lived in England and Wales, without diagnosed asthma and with good-quality spirometry data. Potential airflow obstruction was defined using self-reported physician-diagnosed COPD; a fixed threshold (FT) forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7 and an age-specific, sex-specific, height-specific and ethnic-specific lower limit of normal (LLN). Standardised questions elicited self-reported information on demography, smoking history, ethnicity, occupation, respiratory symptoms and cardiovascular disease.

Results

Consistent across definitions, participants classed with obstructed airflow were more likely to be older, currently smoke, have higher pack-years of smoking and be engaged in routine occupations. The prevalence of airflow obstruction was 2.8% (95% CI 2.3% to 3.2%), 22.2% (21.2% to 23.2%) and 13.1% (12.2% to 13.9%) according to diagnosed COPD, FT and LLN, respectively. The gap in prevalence between FT and LLN increased in older age groups. Sex differences in the risk of obstruction, after adjustment for key risk factors, was sensitive to the choice of spirometric cut-off, being significantly higher in men when using FT, compared with no significant difference using LLN.

Conclusions

Applying FT or LLN spirometric cut-offs gives a different picture of the size and distribution of the disease burden. Longitudinal studies examining differences in unscheduled hospital admissions and risk of death between FT and LLN may inform the choice as to the best way to include spirometry in assessments of airflow obstruction.
Why Lean doesn't work for everyone
Authors: Kaplan Gary S , Patterson Sarah H , Ching Joan M , Blackmore C Craig
Published: July 2014

Popularisation of Lean in healthcare has led to emphasis on Lean quality improvement tools in isolation, with inconsistent results. We argue that delivery of safer, more efficient, and higher quality-patient focused care requires organisational transformation of which the Lean toolkit is only one component. To successfully facilitate system transformation toward higher quality care at lower cost, Lean tools must be part of a comprehensive management system, within a supportive institutional culture, and with committed leadership.
Shortened Lung Clearance Index is a repeatable and sensitive test in children and adults with cystic fibrosis
Authors: Hannon David , Bradley Judy M , Bradbury Ian , Bell Nicholas , Elborn J Stuart , O'Neill Katherine
Published: July 2014

Background

Lung clearance index (LCI) derived from sulfur hexafluoride (SF6) multiple breath washout (MBW) is a sensitive measure of lung disease in people with cystic fibrosis (CF). However, it can be time-consuming, limiting its use clinically.

Aim

To compare the repeatability, sensitivity and test duration of LCI derived from washout to 1/30th (LCI1/30), 1/20th (LCI1/20) and 1/10th (LCI1/10) to ‘standard’ LCI derived from washout to 1/40th initial concentration (LCI1/40).

Methods

Triplicate MBW test results from 30 clinically stable people with CF and 30 healthy controls were analysed retrospectively. MBW tests were performed using 0.2% SF6and a modified Innocor device. All LCI end points were calculated using SimpleWashout software. Repeatability was assessed using coefficient of variation (CV%). The proportion of people with CF with and without abnormal LCI and forced expiratory volume in 1 s (FEV1) % predicted was compared. Receiver operating characteristic (ROC) curve statistics were calculated. Test duration of all LCI end points was compared using paired t tests.

Results

In people with CF, LCI1/40CV% (p=0.16), LCI1/30CV%,(p=0.53), LCI1/20CV% (p=0.14) and LCI1/10CV% (p=0.25) was not significantly different to controls. The sensitivity of LCI1/40, LCI1/30and LCI1/20to the presence of CF was equal (67%). The sensitivity of LCI1/10and FEV1% predicted was lower (53% and 47% respectively). Area under the ROC curve (95% CI) for LCI1/40, LCI1/30, LCI1/20, LCI1/10and FEV1% predicted was 0.89 (0.80 to 0.97), 0.87 (0.77 to 0.96), 0.87 (0.78 to 0.96), 0.83 (0.72 to 0.94) and 0.73 (0.60 to 0.86), respectively. Test duration of LCI1/30, LCI1/20and LCI1/10was significantly shorter compared with the test duration of LCI1/40in people with CF (p<0.0001) equating to a 5%, 9% and 15% time saving, respectively.

Conclusions

In this study, LCI1/20was a repeatable and sensitive measure with equal diagnostic performance to LCI1/40. LCI1/20was shorter, potentially offering a more feasible research and clinical measure.
The role of computed tomography in the assessment of dental disease in 66 guinea pigs
Authors: Schweda M. C. , Hassan J. , Böhler A. , Tichy A. , Reiter A. M. , Künzel F.
Published: July 2014

Sixty‐six guinea pigs with dental disease were presented to the University of Veterinary Medicine, Vienna, Austria, from 2006 to 2010. Almost all patients had a history of eating difficulties (95 per cent) and underwent clinical and oral examination as well as CT of the head. Findings on extra‐ and intraoral examination were asymmetric elongation (n=28) and symmetric bridging (n=24) of cheek teeth, obliquely worn incisors (n=17), palpable lower jaw swellings (n=13), exophthalmos (n=10) and incisor macrodontia (n=6). Eighty per cent of guinea pigs with exophthalmos showed ipsilateral periapical disease of the maxillary cheek teeth on CT. Ninety‐two per cent of patients with palpable lower jaw swellings showed corresponding dental pathologies on CT. Periapical disease of incisors (n=11) and cheek teeth (n=32) were the most common findings on CT. All abnormally large incisors were found on oral examination and CT, but macrodontia of cheek teeth could only be visualised by CT. Deviation of the lower jaw evaluated in awake animals by visual inspection appeared to correlate with cheek teeth abnormalities. Results emphasise the importance of diagnostic imaging, in particular CT, in guinea pigs with dental disease in order to localise lesions and underlying aetiologies.
Vaccination against tuberculosis in badgers and cattle: an overview of the challenges, developments and current research priorities in Great Britain
Authors: Chambers M. A. , Carter S. P. , Wilson G. J. , Jones G. , Brown E. , Hewinson R. G. , Vordermeier M.
Published: July 2014

Bovine tuberculosis (TB) is a significant threat to the cattle industry in England and Wales. It is widely acknowledged that a combination of measures targeting both cattle and wildlife will be required to eradicate bovine TB or reduce its prevalence until European official freedom status is achieved. Vaccination of cattle and/or badgers could contribute to bovine TB control in Great Britain, although there are significant gaps in our knowledge regarding the impact that vaccination would actually have on bovine TB incidence. Laboratory studies have demonstrated that vaccination with BCG can reduce the progression and severity of TB in both badgers and cattle. This is encouraging in terms of the prospect of a sustained vaccination programme achieving reductions in disease prevalence; however, developing vaccines for tackling the problem of bovine TB is challenging, time‐consuming and resource‐intensive, as this review article sets out to explain.
The thermodynamical properties of charged dilaton–axion black hole and its quasi-localized energy
Authors: Yang I-Ching , Huang Wen-Kuei
Published: July 2014

We calculate the heat transfer passing through two horizons of charged dilaton–axion black hole and the quasi-localized energy in the patch ℳ between two horizons. The result EEinstein|ℳ= EMø ller|ℳ-∑∂ℳTS is a Legendre transformation. So that the quasi-localized energy EEinsteinand EMø llerin the patch ℳ could be considered as thermodynamic potentials.
Using High Level Petri Nets in the Modelling, Simulation and Verification of Reconfigurable Manufacturing Systems
Authors: Kahloul Laid , Bourekkache Samir , Djouani Karim , Chaoui Allaoua , Kazar Okba
Published: July 2014

In Reconfigurable Manufacturing Systems (RMSs), the structure of the system can be changed during execution of the system. This reconfiguration can be motivated by a new requirement in the production process, or to avoid some problems caused by machines breakdowns. These systems offer a high flexibility leading to more productivity and efficiency. However, their design is more complicated implying new techniques and paradigms. The use of formal high level Petri Nets offers the ability to design these systems and to analyse or prove their properties. In this paper, we apply Reconfigurable Object Nets (RONs) for the modelling, simulation and analysis of reconfigurable manufacturing systems. We propose a formal approach, where the reconfiguration is specified as graph transformations, the simulation is realized using the RON-tool, and the analysis exploits some software tools such as TINA-tool and PIPE-tool.
Investigation of Developer's Perceptions in XML Schema Development Using Textual and Visual Tool Types
Authors: Pušnik Maja , Pulko Katja Harej , Heričko Marjan , Jurič Matjaž B. , Šumak Boštjan
Published: July 2014

This paper analyses the influence of different tool types (visual or textual) on a developer's perception of efficiency during XML Schema development. We conducted a controlled experiment that focused on discovering which XML Schema development tool type enables better efficiency and also engenders a friendlier environment for developers while developing XML Schemas. The experiment was conducted with 240 participants and divided into two practical parts (visually developing an XML Schema and manually using a mark-up language intelligent textual editor). After the experiment, the participants' opinions were gathered via a web survey. In the survey, a technology acceptance model (TAM) was used as the basis for constructing the measurement items in order to answer the following questions: (1) which tool type is preferred and perceived as better, and (2) which variables influence the user's perceptions and decisions. In this study, we searched for an optimal way of building XML Schemas. The general tendency of most participants was towards a visual tool, suggesting that visual support is perceived as more useful, and can create better results with less effort.
Three-dimensional self-supported metal oxides as cathodes for microbatteries
Authors: Xiong Wen , Xia Qiuying , Xia Hui
Published: July 2014

Microbatteries are currently the best choice to power microelecronic devices. To maximize both energy density and power density of microbatteries within the areal footprint, the three-dimensional (3D) microbattery architectures have been proposed, comprising a 3D matrix of components (cathode, anode and electrolyte) arranged in either a periodic array or an aperiodic ensemble. As one of the key components, the cathode is vital to the electrochemical performance of microbatteries and the fabrication of 3D cathode is still challenging. This review describes recent advances in the development of 3D self-supported metal oxides as cathodes for lithium-ion microbatteries. Current technologies for the design and morphology control of 3D cathode fabricated using template, laser structuring and 3D printing are outlined along with different efforts to improve the energy and power densities.
Super-Solutions
Authors: Molinaro Cristian , Sliva Amy , Subrahmanian V. S.
Published: July 2014

Annotated Probabilistic Temporal (APT) logic programs are a form of logic programs that allow users to state (or systems to automatically learn) rules of the form “formula
G
becomes true Δ
t
time units after formula
F
became true with ℓ to
u
% probability.” In this article, we deal with abductive reasoning in APT logic: given an APT logic program Π, a set of formulas
H
that can be “added” to Π, and a (temporal) goal
g
, is there a subset
S
of
H
such that Π ∪
S
is consistent and entails the goal
g
? In general, there are many different solutions to the problem and some of them can be highly repetitive, differing only in some unimportant temporal aspects. We propose a compact representation called
super-solutions
that succinctly represent
sets
of such solutions. Super-solutions are compact, but lossless representations of sets of such solutions. We study the complexity of existence of basic, super-, and maximal super-solutions as well as check if a set is a solution/super-solution/maximal super-solution. We then leverage a geometric characterization of the problem to suggest a set of pruning strategies and interesting properties that can be leveraged to make the search of basic and super-solutions more efficient. We propose correct sequential algorithms to find solutions and super-solutions. In addition, we develop parallel algorithms to find basic and super-solutions.
Researchers probe security through obscurity
Authors: Edwards Chris
Published: July 2014

Obfuscation protects code by making it so impenetrable that access to it won't help a hacker understand how it works.
Surgical robots deliver care more precisely
Authors: Kirkpatrick Keith
Published: July 2014

Computer-controlled robotic surgical systems and tumor-targeting radiation systems provide a greater level of precision in treatment than doctors alone can provide.
Undergraduate software engineering
Authors: Lutz Michael J. , Naveda J. Fernando , Vallino James R.
Published: July 2014

Addressing the needs of professional software development.
Can you engineer privacy?
Authors: Gürses Seda
Published: July 2014

The challenges and potential approaches to applying privacy research in engineering practice.
Epidermal growth factor-induced proliferation of collecting duct cells from Oak Ridge polycystic kidney mice involves activation of Na+/H+ exchanger
Authors: Coaxum Sonya D. , Blanton Mary G. , Joyner Alisha , Akter Tanjina , Bell P. Darwin , Luttrell Louis M. , Raymond John R. , Lee Mi-Hye , Blichmann Paul A. , Garnovskaya Maria N. , Saigusa Takamitsu
Published: July 2014

Epidermal growth factor (EGF) is linked to the pathogenesis of polycystic kidney disease (PKD). We explored signaling pathways activated by EGF in orpk cilia (−) collecting duct cell line derived from a mouse model of PKD (hypomorph of the Tg737/ Ift88 gene) with severely stunted cilia, and in a control orpk cilia (+) cell line with normal cilia. RT-PCR demonstrated mRNAs for EGF receptor subunits ErbB1, ErbB2, ErbB3, ErbB4, and mRNAs for Na+/H+ exchangers (NHE), NHE-1, NHE-2, NHE-3, NHE-4, and NHE-5 in both cell lines. EGF stimulated proton efflux in both cell lines. This effect was significantly attenuated by MIA, 5-( n-methyl- N-isobutyl) amiloride, a selective inhibitor of NHE-1 and NHE-2, and orpk cilia (−) cells were more sensitive to MIA than control cells ( P < 0.01). EGF significantly induced extracellular signal-regulated kinase (ERK) phosphorylation in both cilia (+) and cilia (−) cells (63.3 and 123.6%, respectively), but the effect was more pronounced in orpk cilia (−) cells ( P < 0.01). MIA significantly attenuated EGF-induced ERK phosphorylation only in orpk cilia (−) cells ( P < 0.01). EGF increased proliferation of orpk cilia (+) cells and orpk cilia (−) cells, respectively, and MIA at 1–5 μM attenuated EGF-induced proliferation in orpk cilia (−) cells without affecting proliferation of orpk cilia (+) cells. EGF-induced proliferation of both cell lines was significantly decreased by the EGFR tyrosine kinase inhibitor AG1478 and MEK inhibitor PD98059. These results suggest that EGF exerts mitogenic effects in the orpk cilia (−) cells via activation of growth-associated amiloride-sensitive NHEs and ERK.
Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature
Authors: Carver Koryn A. , Lourim David , Tryba Andrew K. , Harder David R.
Published: July 2014

Mammals have circadian variation in blood pressure, heart rate, vascular tone, thrombotic tendency, and cerebral blood flow (CBF). These changes may be in part orchestrated by circadian variation in clock gene expression within cells comprising the vasculature that modulate blood flow (e.g., fibroblasts, cerebral vascular smooth muscle cells, astrocytes, and endothelial cells). However, the downstream mechanisms that underlie circadian changes in blood flow are unknown. Cytochrome P450 epoxygenases (Cyp4x1 and Cyp2c11) are expressed in the brain and vasculature and metabolize arachidonic acid (AA) to form epoxyeicosatrienoic acids (EETs). EETs are released from astrocytes, neurons, and vascular endothelial cells and act as potent vasodilators, increasing blood flow. EETs released in response to increases in neural activity evoke a corresponding increase in blood flow known as the functional hyperemic response. We examine the hypothesis that Cyp2c11 and Cyp4x1 expression and EETs production vary in a circadian manner in the rat brain and cerebral vasculature. RT-PCR revealed circadian/diurnal expression of clock and clock-controlled genes as well as Cyp4x1 and Cyp2c11, within the rat hippocampus, middle cerebral artery, inferior vena cava, hippocampal astrocytes and rat brain microvascular endothelial cells. Astrocyte and endothelial cell culture experiments revealed rhythmic variation in Cyp4x1 and Cyp2c11 gene and protein expression with a 12-h period and parallel rhythmic production of EETs. Our data suggest there is circadian regulation of Cyp4x1 and Cyp2c11 gene expression. Such rhythmic EETs production may contribute to circadian changes in blood flow and alter risk of adverse cardiovascular events throughout the day.
In vitro assessment of mouse fetal abdominal aortic vascular function
Authors: Renshall Lewis J. , Dilworth Mark R. , Greenwood Susan L. , Sibley Colin P. , Wareing Mark
Published: July 2014

Fetal growth restriction (FGR) affects 3–8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. We developed a wire myography methodology for evaluation of fetal vascular function in vitro using the placenta-specific insulin-like growth factor II ( Igf2) knockout mouse (P0; a model of FGR). Vascular function was determined in abdominal aortas isolated from P0 and wild-type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams received SC 0.8 mg/ml via drinking water from E12.5; data were compared with water-only controls. Using wire myography, we found that fetal aortic rings exhibited significant agonist-induced contraction, and endothelium-dependent and endothelium-independent relaxation. Sex-specific alterations in reactivity were noted in both strains. Maternal treatment with SC significantly attenuated endothelium-dependent and endothelium-independent relaxation of fetal aortic rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents. Study of these vessels in mouse genetic models of pregnancy complications may 1) help to delineate early signs of abnormal vascular reactivity and 2) inform whether treatments given to the mother during pregnancy may impact upon fetal vascular function.
A knowledge base of vasopressin actions in the kidney
Authors: Sanghi Akshay , Zaringhalam Matthew , Corcoran Callan C. , Saeed Fahad , Hoffert Jason D. , Sandoval Pablo , Pisitkun Trairak , Knepper Mark A.
Published: July 2014

Biological information is growing at a rapid pace, making it difficult for individual investigators to be familiar with all information that is relevant to their own research. Computers are beginning to be used to extract and curate biological information; however, the complexity of human language used in research papers continues to be a critical barrier to full automation of knowledge extraction. Here, we report a manually curated knowledge base of vasopressin actions in renal epithelial cells that is designed to be readable either by humans or by computer programs using natural language processing algorithms. The knowledge base consists of three related databases accessible at https://helixweb.nih.gov/ESBL/TinyUrls/Vaso_portal.html . One of the component databases reports vasopressin actions on individual proteins expressed in renal epithelia, including effects on phosphorylation, protein abundances, protein translocation from one subcellular compartment to another, protein-protein binding interactions, etc. The second database reports vasopressin actions on physiological measures in renal epithelia, and the third reports specific mRNA species whose abundances change in response to vasopressin. We illustrate the application of the knowledge base by using it to generate a protein kinase network that connects vasopressin binding in collecting duct cells to physiological effects to regulate the water channel protein aquaporin-2.
Extrarenal citrulline disposal in mice with impaired renal function
Authors: Marini Juan C. , Didelija Inka C. , Fiorotto Marta L.
Published: July 2014

The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the “intestinal-renal axis” for arginine synthesis. Although the kidney is the main site for citrulline disposal, it only accounts for ∼60–70% of the citrulline produced. Because the only known fate for citrulline is arginine synthesis and the enzymes that catalyze this reaction are widespread among body tissues, we hypothesized that citrulline can be utilized directly by tissues to meet, at least partially, their arginine needs. To test this hypothesis, we used stable and radioactive tracers in conscious, partially nephrectomized (½ and ⅚) and anesthetized acutely kidney-ligated mouse models. Nephrectomy increased plasma citrulline concentration but did not affect citrulline synthesis rates, thus reducing its clearance. Nephrectomy (⅚) reduced the amount of citrulline accounted for as plasma arginine from 88 to 42%. Acute kidney ligation increased the half-life and mean retention time of citrulline. Whereas the rate of citrulline conversion into plasma arginine was reduced, it was not eliminated. In addition, we observed direct utilization of citrulline for arginine synthesis and further incorporation into tissue protein in kidney-ligated mice. These observations indicate that a fraction of the citrulline produced is utilized directly by multiple tissues to meet their arginine needs and that extrarenal sites contribute to plasma arginine. Furthermore, when the interorgan synthesis of arginine is impaired, these extrarenal sites are able to increase their rate of citrulline utilization.
Renal PKC-ε deficiency attenuates acute kidney injury and ischemic allograft injury via TNF-α-dependent inhibition of apoptosis and inflammation
Authors: Rong Song , Hueper Katja , Kirsch Torsten , Greite Robert , Klemann Christian , Mengel Michael , Meier Matthias , Menne Jan , Leitges Michael , Susnik Nathan , Meier Martin , Haller Hermann , Shushakova Nelli , Gueler Faikah
Published: July 2014

Acute kidney injury (AKI) increases the risk of morbidity and mortality after major surgery and transplantation. We investigated the effect of PKC-ε deficiency on AKI and ischemic allograft damage after kidney transplantation. PKC-ε-deficient and wild type (WT) control mice were subjected to 35 min of renal pedicle clamping to induce AKI. PKC-ε deficiency was associated with a marked improvement in survival and an attenuated loss of kidney function. Furthermore, functional MRI experiments revealed better renal perfusion in PKC-ε-deficient mice than in WT mice one day after IRI. Acute tubular necrosis and neutrophil infiltration were markedly reduced in PKC-ε-deficient mice. To determine whether this resistance to ischemia-reperfusion injury resulted from changes in local renal cells or infiltrating leukocytes, we studied a life-supporting renal transplant model of ischemic graft injury. We transplanted kidneys from H2b PKC-ε-deficient mice (129/SV) and their corresponding WT littermates into major histocompatibility complex-incompatible H2d recipients (BALB/c) and induced ischemic graft injury by prolonged cold ischemia time. Recipients of WT allografts developed severe renal failure and died within 10 days of transplantation. Recipients of PKC-ε-deficient allografts had better renal function and survival; they had less generation of ROS and upregulation of proinflammatory proteins (i.e., ICAM-1, inducible nitric oxide synthase, and TNF-α) and showed less tubular epithelial cell apoptosis and inflammation in their allografts. These data suggest that local renal PKC-ε expression mediates proapoptotic and proinflammatory signaling and that an inhibitor of PKC-ε signaling could be used to prevent hypoxia-induced AKI.
Nanotechnology and adeno-associated virus-based decorin gene therapy ameliorates peritoneal fibrosis
Authors: Chaudhary Kunal , Moore Harold , Tandon Ashish , Gupta Suneel , Khanna Ramesh , Mohan Rajiv R.
Published: July 2014

Peritoneal dialysis (PD) is a life-sustaining therapy for end-stage renal disease (ESRD), used by 10–15% of the dialysis population worldwide. Peritoneal fibrosis (PF) is a known complication of long-term PD and frequently follows episodes of peritonitis, rendering the peritoneal membrane inadequate for dialysis. Transforming growth factor (TGF)-β is an inducer of fibrosis in several tissues and organs, and its overexpression has been correlated with PF. Animal models of peritonitis have shown an increase in expression of TGF-β in the peritoneal tissue. Decorin, a proteoglycan and component of the extracellular matrix, inactivates TGF-β, consequently reducing fibrosis in many tissues. Recently, gold nanoparticles (GNP) have been used for drug delivery in a variety of settings. In the present study, we tested the possibility that GNP-delivered decorin gene therapy ameliorates zymosan-mediated PF. We created a PF model using zymosan-induced peritonitis. Rats were treated with no decorin, GNP-decorin, or adeno-associated virus-decorin (AAV-decorin) and compared with controls. Tissue samples were then stained for Masson's trichrome, enface silver, and hematoxylin and eosin, and immunohistochemistry was carried out with antibodies to TGF-β1, α-smooth muscle actin (α-SMA), and VEGF. Animals which were treated with GNP-decorin and AAV-decorin gene therapy had significant reductions in PF compared with untreated animals. Compared with untreated animals, the treated animals had better preserved peritoneal mesothelial cell size, a significant decrease in peritoneal thickness, and decreased α-SMA. Quantitative PCR measurements showed a significant decrease in the peritoneal tissue levels of α-SMA, TGF-β, and VEGF in treated vs. untreated animals. This study shows that both GNP-delivered and AAV-mediated decorin gene therapies significantly decrease PF in vivo in a rodent model. This approach has important clinical translational potential in providing a therapeutic strategy to prevent PF in PD patients.
Spectral receptive fields do not explain tuning for boundary curvature in V4
Authors: Oleskiw Timothy D. , Pasupathy Anitha , Bair Wyeth
Published: July 2014

The midlevel visual cortical area V4 in the primate is thought to be critical for the neural representation of visual shape. Several studies agree that V4 neurons respond to contour features, e.g., convexities and concavities along a shape boundary, that are more complex than the oriented segments encoded by neurons in the primary visual cortex. Here we compare two distinct approaches to modeling V4 shape selectivity: one based on a spectral receptive field (SRF) map in the orientation and spatial frequency domain and the other based on a map in an object-centered angular position and contour curvature space. We test the ability of these two characterizations to account for the responses of V4 neurons to a set of parametrically designed two-dimensional shapes recorded previously in the awake macaque. We report two lines of evidence suggesting that the SRF model does not capture the contour sensitivity of V4 neurons. First, the SRF model discards spatial phase information, which is inconsistent with the neuronal data. Second, the amount of variance explained by the SRF model was significantly less than that explained by the contour curvature model. Notably, cells best fit by the curvature model were poorly fit by the SRF model, the latter being appropriate for a subset of V4 neurons that appear to be orientation tuned. These limitations of the SRF model suggest that a full understanding of midlevel shape representation requires more complicated models that preserve phase information and perhaps deal with object segmentation.
Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in hippocampal area CA1 of adult rats and mice
Authors: Cao Guan , Harris Kristen M.
Published: July 2014

Hippocampal long-term potentiation (LTP) is a model system for studying cellular mechanisms of learning and memory. Recent interest in mechanisms underlying the advantage of spaced over massed learning has prompted investigation into the effects of distributed episodes of LTP induction. The amount of LTP induced in hippocampal area CA1 by one train (1T) of theta-burst stimulation (TBS) in young Sprague-Dawley rats was further enhanced by additional bouts of 1T given at 1-h intervals. However, in young Long-Evans (LE) rats, 1T did not initially saturate LTP. Instead, a stronger LTP induction paradigm using eight trains of TBS (8T) induced saturated LTP in hippocampal slices from both young and adult LE rats as well as adult mice. The saturated LTP induced by 8T could be augmented by another episode of 8T following an interval of at least 90 min. The success rate across animals and slices in augmenting LTP by an additional episode of 8T increased significantly with longer intervals between the first and last episodes, ranging from 0% at 30- and 60-min intervals to 13–66% at 90- to 180-min intervals to 90–100% at 240-min intervals. Augmentation above initially saturated LTP was blocked by the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist d-2-amino-5-phosphonovaleric acid (d-APV). These findings suggest that the strength of induction and interval between episodes of TBS, as well as the strain and age of the animal, are important components in the augmentation of LTP.
Unilateral whisker trimming in newborn rats alters neuronal coincident discharge among mature barrel cortex neurons
Authors: Ghoshal Ayan , Lustig Brian , Popescu Maria , Ebner Ford , Pouget Pierre
Published: July 2014

It is known that sensory deprivation, including postnatal whisker trimming, can lead to severe deficits in the firing rate properties of cortical neurons. Recent results indicate that development of synchronous discharge among cortical neurons is also activity influenced, and that correlated discharge is significantly impaired following loss of bilateral sensory input in rats. Here we investigate whether unilateral whisker trimming (unilateral deprivation or UD) after birth interferes in the same way with the development of synchronous discharge in cortex. We measured the coincidence of spikes among pairs of neurons recorded under urethane anesthesia in one whisker barrel field deprived by trimming all contralateral whiskers for 60 days after birth (UD), and in untrimmed controls (CON). In the septal columns around barrels, UD significantly increased the coincident discharge among cortical neurons compared with CON, most notably in layers II/III. In contrast, synchronous discharge was normal between layer IV UD barrel neurons: i.e., not different from CON. Thus, while bilateral whisker deprivation (BD) produced a global deficit in the development of synchrony in layer IV, UD did not block the development of synchrony between neurons in layer IV barrels and increased synchrony within septal circuits. We conclude that changes in synchronous discharge after UD are unexpectedly different from those recorded after BD, and we speculate that this effect may be due to the driven activity from active commissural inputs arising from the contralateral hemisphere that received normal activity levels during postnatal development.
Analyzing Density Operator in Thermal State for Complicated Time-Dependent Optical Systems
Authors: Choi Jeong Ryeol , Song Ji Nny , Choi Yeontaek
Published: July 2014

Density operator of oscillatory optical systems with time-dependent parameters is analyzed. In this case, a system is described by a time-dependent Hamiltonian. Invariant operator theory is introduced in order to describe time-varying behavior of the system. Due to the time dependence of parameters, the frequency of oscillation, so-called a modified frequency of the system, is somewhat different from the natural frequency. In general, density operator of a time-dependent optical system is represented in terms of the modified frequency. We showed how to determine density operator of complicated time-dependent optical systems in thermal state. Usually, density operator description of quantum states is more general than the one described in terms of the state vector.
Transparent Electrodes with Nanotubes and Graphene for Printed Optoelectronic Applications
Authors: Słoma Marcin , Wróblewski Grzegorz , Janczak Daniel , Jakubowska Małgorzata
Published: July 2014

We report here on printed electroluminescent structures containing transparent electrodes made of carbon nanotubes and graphene nanoplatelets. Screen‐printing and spray‐coating techniques were employed. Electrodes and structures were examined towards optical parameters using spectrophotometer and irradiation meter. Electromechanical properties of transparent electrodes are exterminated with cyclical bending test. Accelerated aging process was conducted according to EN 62137 standard for reliability tests of electronics. We observed significant negative influence of mechanical bending on sheet resistivity of ITO, while resistivity of nanotube and graphene based electrodes remained stable. Aging process has also negative influence on ITO based structures resulting in delamination of printed layers, while those based on carbon nanomaterials remained intact. We observe negligible changes in irradiation for structures with carbon nanotube electrodes after accelerated aging process. Such materials demonstrate a high application potential in general purpose electroluminescent devices.
Assessment of theE-Selectinrs5361 (561A>C) Polymorphism and Soluble Protein Concentration in Acute Coronary Syndrome: Association with Circulating Levels
Authors: Sandoval-Pinto Elena , Ramon Padilla-Gutiérrez Jorge , Valdes-Alvarado Emmanuel , Janet García-González Ilian , Valdez-Haro Angelica , Francisco Muñoz-Valle Jose , Enrique Flores-Salinas Hector , Rivas Fernando , Valle Yeminia
Published: July 2014

Introduction. The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved.E-selectingene is a candidate for ACS progression due to its contribution in the inflammatory process and endothelial function. The rs5361 (561A>C) polymorphism in theE-selectingene has been linked to changes in gene expression, affinity for its receptor, and plasmatic levels; therefore it is associated with an increased risk of cardiovascular disease. The aim of this study was to determine the association of the rs5361 polymorphism with ACS and to measure serum levels of soluble E-selectin (sE-selectin).Materials and Methods. 283 ACS patients and 205 healthy subjects (HS) from Western Mexico were included. The polymerase chain reaction-restriction fragment length polymorphism was used to determine the rs5361 polymorphism. The sE-selectin levels were measured by enzyme-linked immunosorbent assay.Results. Neither genotype nor allele frequencies of the rs5361 polymorphism showed statistical differences between groups. The sE-selectin levels were significantly higher in ACS patients compared to HS (54.58 versus 40.41 ng/ml,P=0.02). The C allele had no effect on sE-selectin levels.Conclusions. The rs5361E-selectingene polymorphism is not a susceptibility marker for ACS in Western Mexico population. However, sE-selectin may be a biological marker of ACS.
Cephalometric Investigation of First Cervical Vertebrae Morphology and Hyoid Position in Young Adults with Different Sagittal Skeletal Patterns
Authors: Gündüz Arslan Seher , Dildeş Neval , Devecioglu Kama Jalen
Published: July 2014

The aim of this retrospective study was to examine hyoid bone position and C1 (atlas) morphology in males and females and analyze these parameters with respect to different sagittal skeletal patterns via cephalometry, with the goal of identifying cephalometric norms. Lateral cephalometric radiographs from 120 individuals (average age: 21.1 ± 2.9 years) were classified according to their ANB angle (Class I, II, or III) and used to assess 14 parameters. Class I and II patients showed significant differences in Hy-NSL, Hy-PD, Hy-CVT, Lum, and a-p measurements. These parameters were consistently larger in males than in females. Intergroup comparisons among males showed significant differences in the SNA, ANB, Hy-CVT, X, and Z measurements. The hyoid was positioned more inferiorly and anteriorly and was more prominent in males than in females in all groups. Among participants exhibiting a Class I skeletal pattern, C1 was also larger in the anterior-posterior direction in males than in females. In the sagittal plane, the hyoid was positioned similarly in males with either Class I or III skeletal patterns but was positioned posteriorly in males with a Class II skeletal pattern. In addition, the vertical position of C1 varied with sagittal skeletal pattern in males.