bluuebunny/crossref_metadata_2025 huggingface dataset:
There's no place like home: 35‐year patient survival on home hemodialysis
Authors: Yu Jerry Z. , Rhee Connie M. , Ferrey Antoney , Li Alex , Jin Anna , Chang Yongen , Reddy Uttam , Lau Wei Ling , Chou Jason , Inrig Jula , Kalantar‐Zadeh Kamyar
Published: December 2017

The vast majority of maintenance dialysis patients suffer from poor long‐term survival rates and lower levels of health‐related quality of life. However, home hemodialysis is a historically significant dialysis modality that has been associated with favorable outcomes as well as greater patient autonomy and control, yet only represents a small minority of the total dialysis performed in the United States. Some potential disadvantages of home hemodialysis include vascular access complications, infection‐related hospitalizations, patient fatigue, and attrition. In addition, current barriers and challenges in expanding the utilization of this modality include limited patient and provider education and technical expertise. Here we report a 65‐year old male with end‐stage renal disease due to Alport's syndrome who has undergone 35 years of uninterrupted thrice‐weekly home hemodialysis (ie, every Sunday, Tuesday, and Thursday evening, each session lasting 3 to 3¼ hours in length) using a conventional hemodialysis machine who has maintained a high functional status allowing him to work 6‐8 hours per day. The patient has been able to liberalize his dietary and fluid intake while only requiring 3‐4 liters of ultrafiltration per treatment, despite having absence of residual kidney function. Through this case of extraordinary longevity and outcomes after 35 years of dialysis and a review of the literature, we illustrate the history of home hemodialysis, its significant clinical and psychosocial advantages, as well as the barriers that hinder its widespread adaptation.
The use of next‐generation sequencing for the determination of rare blood group genotypes
Authors: Jakobsen M. A. , Dellgren C. , Sheppard C. , Yazer M. , Sprogøe U.
Published: December 2017

Objectives

Next‐generation sequencing (NGS) for the determination of rare blood group genotypes was tested in 72 individuals from different ethnicities.

Background

Traditional serological‐based antigen detection methods, as well as genotyping based on specific single nucleotide polymorphisms (SNPs) or single nucleotide variants (SNVs), are limited to detecting only a limited number of known antigens or alleles. NGS methods do not have this limitation.

Methods

NGS using Ion torrent Personal Genome Machine (PGM) was performed with a customised Ampliseq panel targeting 15 different blood group systems on 72 blood donors of various ethnicities (Caucasian, Hispanic, Asian, Middle Eastern and Black).

Results

Blood group genotypes for 70 of 72 samples could be obtained for 15 blood group systems in one step using the NGS assay and, for common SNPs, are consistent with previously determined genotypes using commercial SNP assays. However, particularly for the Kidd, Duffy and Lutheran blood group systems, several SNVs were detected by the NGS assay that revealed additional coding information compared to other methods. Furthermore, the NGS assay allowed for the detection of genotypes related to VEL, Knops, Gerbich, Globoside, P1PK and Landsteiner‐Wiener blood group systems.

Conclusions

The NGS assay enables a comprehensive genotype analysis of many blood group systems and is capable of detecting common and rare alleles, including alleles not currently detected by commercial assays.
High diversity of medically important gastrointestinal rodent‐borne helminths in Singapore
Authors: Mendenhall I. H. , Ch'ng L. , Neves E. S. , Borthwick S. A. , Smith G. J. D.
Published: December 2017

Small mammals are important reservoirs of zoonotic diseases and are definitive hosts for medically important parasitic helminths. Several rodent and shrew species are peridomestic, bringing them into close contact with both humans and the intermediate hosts that maintain the transmission cycle. Here, we screened DNA extracted from large intestine tissue homogenate from 108 individuals comprised of 10 species. We detected two species known to infect humans, Dicrocoelium dendriticum and Moniliformis moniliformis. We also report the first detection of a second Angiostrongylus species in Singapore. This study demonstrates the diversity of helminths that are parasitizing the small mammals in Singapore.
Macroeconomic Effects of Fiscal Policy in Morocco: An Approach to Structural VAR
Authors: Bahaddi Tlaytmaste , Karim Mohamed
Published: December 2017

This article evaluates the short-term macroeconomic effectiveness of a structural rise in public spending in Morocco through a Structural Vector Autoregressive Model (SVAR) inspired by the approach of Blanchard and Perotti (2002).The response of the real economic activity following a structural rise of the public spending is small and significant only in the very short term. The evaluation of transmission channels reveals, moreover, a deterioration of the trade balance and a depreciation of the real effective exchange rate. Finally, the results of the estimation concluded that discretionary fiscal shocks have a Keynesian effect on the level of activity.
Thermal Performance Evaluation of Textile Waste as an Alternative Solution for Heat Transfer Reduction in Buildings
Authors: Gounni Ayoub , El Wazna Mohamed , El Alami Mustapha , El Bouari Abdeslam , Cherkaoui Omar , Mabouk Mohamed Tahar , Kheiri Abdelhamid
Published: December 2017

The potential applicability of a developed recycled textile material, based on acrylic spinning waste, as thermal insulation is conducted. The prepared acrylic spinning waste (AS) is thermo-physically characterized in terms of density, air permeability, and thermal conductivity. The results show that the density and air permeability are 10.583 kg/m3 and 1100 L/m2/s, respectively. In addition, the thermal conductivity is found to be 38.27 mW/(m K). The developed thermal insulator is then tested in a thermally controlled reduced scale cavity. Two walls of the cavity are outfitted with AS at two different locations and compared to the walls without AS. The comparison is made based on the wall surface temperature and heat flux. A reduction in surface temperature is observed in the walls outfitted with AS, compared to wall without AS. Indeed, compared to a control wall, the peak heat fluxes are reduced by 27.23% and 18.67%, respectively, related to the walls with AS at location 1 and location 2. The obtained results show that the AS is a competitive thermal insulation material and can increase the thermal performance of the building walls.
A Short History of Bioengineering Research in Ireland
Authors: Kelly Daniel J. , O'Brien Fergal J. , Prendergast Patrick J.
Published: December 2017

In July 2018, Ireland will host the World Congress of Biomechanics in Dublin. This Congress is held once every 4 yr and is the premier meeting worldwide in its field, with over 3000 people expected to visit Dublin in July. The awarding of the 2018 Congress to Ireland is a reflection of the strength of biomechanics and bioengineering research in this country. To mark this event, herein we describe the development of biomechanics and bioengineering research in Ireland over the past 40 yr, which has grown in parallel with the medical device industry as well as the expansion of Government investment in science, innovation, and a knowledge-based economy. The growth of this activity has resulted in Ireland becoming established as a global hub in the field.
Twenty-four-micrometer-pitch microelectrode array with 6912-channel readout at 12 kHz via highly scalable implementation for high-spatial-resolution mapping of action potentials
Authors: Ogi Jun , Kato Yuri , Matoba Yoshihisa , Yamane Chigusa , Nagahata Kazunori , Nakashima Yusaku , Kishimoto Takuya , Hashimoto Shigeki , Maari Koichi , Oike Yusuke , Ezaki Takayuki
Published: December 2017

A 24-μm-pitch microelectrode array (MEA) with 6912 readout channels at 12 kHz and 23.2-μVrms random noise is presented. The aim is to reduce noise in a “highly scalable” MEA with a complementary metal-oxide-semiconductor integration circuit (CMOS-MEA), in which a large number of readout channels and a high electrode density can be expected. Despite the small dimension and the simplicity of the in-pixel circuit for the high electrode-density and the relatively large number of readout channels of the prototype CMOS-MEA chip developed in this work, the noise within the chip is successfully reduced to less than half that reported in a previous work, for a device with similar in-pixel circuit simplicity and a large number of readout channels. Further, the action potential was clearly observed on cardiomyocytes using the CMOS-MEA. These results indicate the high-scalability of the CMOS-MEA. The highly scalable CMOS-MEA provides high-spatial-resolution mapping of cell action potentials, and the mapping can aid understanding of complex activities in cells, including neuron network activities.
High-rate sputter deposition of electrochromic nickel oxide thin films using substrate cooling and water vapor injection
Authors: Abe Yoshio , Yamauchi Shun , Kawamura Midori , Kim Kyung Ho , Kiba Takayuki
Published: December 2017

Nickel oxide is a promising electrochromic (EC) material because it changes color upon electrochemical oxidation and reduction. In this study, the authors developed a reactive sputtering technique using water vapor as a reactive gas to deposit highly hydrated oxide thin films. They used an Ar+H2O gas mixture, with H2O injected directly onto the substrate surface. Subsequently, the authors studied the effects of substrate cooling on the mechanism of Ni oxide thin film formation and how this process affected the EC properties of the resulting Ni oxide thin films. At substrate temperatures of −80 and −120 °C, amorphous hydrated Ni oxide thin films were deposited with a high deposition rate of approximately 35 nm/min, which was greater than that of metallic Ni films. It was surmised that the metallic target mode was achieved at low substrate temperatures in the Ar+H2O atmosphere. The Ni oxide films exhibited good EC properties with a large transmittance change. Consequently, substrate cooling and water vapor injection were found to be effective in the high-rate deposition of Ni oxide thin films with good EC properties.
Spatial molecular layer deposition of polyamide thin films on flexible polymer substrates using a rotating cylinder reactor
Authors: Higgs Daniel J. , DuMont Jaime W. , Sharma Kashish , George Steven M.
Published: December 2017

Polyamide thin films were rapidly grown using spatial molecular layer deposition (MLD) in a rotating cylinder reactor. The polyamide MLD films were coated on flexible metalized polyethylene terephthalate substrates using sequential exposures of trimesoyl chloride (TMC) and m-phenylenediamine (mPD). The rotating cylinder reactor was housed in a custom oven enclosure that maintained a constant temperature of 115 °C. One MLD cycle (TMC/mPD) was performed per rotation of the cylinder. Polyamide growth rates of 4.5 Å/cycle or 90 Å/min were observed at a slow rotation speed of 20 revolutions per minute (RPM) at a substrate speed of 0.33 m/s. Growth rates of 2.27 Å/cycle or 477 Å/min were measured at higher rotation speeds of 210 RPM at substrate speeds of 3.5 m/s. The polyamide film thicknesses were uniform over the substrate widths as large as ∼16.5 cm. The polyamide MLD surface chemistry was also self-limiting. Constant polyamide growth rate per cycle was measured at larger TMC and mPD exposures. In addition, infrared analysis and thermal annealing studies confirmed the chemical identity of the polyamide films. With four MLD cycles per rotation of the rotating cylinder, spatial MLD should be able to obtain polymer growth rates of >1900 Å/min at a rotation speed of 210 RPM. These rapid growth rates are much higher than the growth rates that can be obtained in temporal MLD reactors. The spatial MLD of polyamide films has many possible applications including the deposition of ultrathin reverse osmosis membranes for water desalination.
Dicarboxylic acids analyzed by time-of-flight secondary ions mass spectrometry. Part V: Heptanedioic acid
Authors: Trindade Gustavo F. , Ferreira Jose M. , Abel Marie-Laure , Baker Mark A. , Watts John F.
Published: December 2017

Time-of-flight secondary ion mass spectrometry was carried out to analyze a commercially available heptanedioic acid (pimelic acid) powder. Positive and negative polarity ion spectra were obtained using a 25 keV Bi3+ ion beam rastered over areas of 50 × 50 μm2. The main observed fragments were the protonated molecule [M+H]+ at 105 u and the deprotonated molecule [M-H]− at 103 Da with their respective oligomers.
Demonstrating the conservation of angular momentum using spherical
magnets
Authors: Lindén Johan , Slotte Joakim , Källman Kjell-Mikael
Published: December 2017

An experimental setup for demonstrating the conservation of angular momentum of rotating spherical magnets is described. Two spherical Nd-Fe-B magnets are placed on a double inclined plane and projected towards each other with pre-selected impact parameters ranging from zero to a few tens of millimeters. After impact, the two magnets either revolve vigorously around the common center of mass or stop immediately, depending on the value of the impact parameter. Using a pick-up coil connected to an oscilloscope, the angular frequency for the rotating magnets was measured, and an estimate for the angular momentum was obtained. A high-speed video camera captured the impact and was used for measuring linear and angular velocities of the magnets. A very good agreement between the initial angular momentum before the impact and the final angular momentum of the revolving dumbbell is observed. The two rotating magnets, and the rotating electromagnetic field emanating from them, can also be viewed as a toy model for the newly discovered gravitational waves, where two black holes collide after revolving around each other. (Enhanced online)
Characterization of interface reflection coefficients using a finite-difference injection technique
Authors: Börsing Nele , Donahue Carly M. , van Manen Dirk-Jan , Amundsen Lasse , Robertsson Johan O. A.
Published: December 2017

In this paper, a numerical wave field injection technique for characterizing the reflection coefficient of a planar medium interface is proposed. By injecting recorded wave field quantities into a three-dimensional (3D) finite-difference calculation, two key objectives are addressed: first, the recorded wave field is separated into its incident and reflected constituents without the need of spatial Fourier transforms or a temporal separation of incident and reflected parts in the recorded data. Second, the separated constituents are independently extrapolated to the location of the reflecting interface to determine its reflecting properties. The methodology is experimentally validated on 3D laboratory data consisting of reflections from the water-air interface in a water tank and is shown to give accurate results for incidence angles of up to 60°.
Neuromuscular Responses and Physiological Changes During Small-Sided Games in Wheelchair Basketball
Authors: Iturricastillo Aitor , Yanci Javier , Granados Cristina
Published: December 2017

The aim was to analyze the changes of physical performance and physiological responses during a high-intensity training task in wheelchair basketball (WB) players. Thirteen Spanish first division WB male players participated in this study. A test battery (change of direction ability, sprints, and sled towing) was performed to study neuromuscular responses before (pre) and after (post) the small-sided games (SSG). Furthermore, tympanic temperature and blood lactate concentration were measured before and immediately after players finished the SSG. The SSG tasks consisted in four players against four, 4 bouts of 4 min with 2 min of recovery periods. There was a 1.10% decline in performance in both 5- and 20-m sprints (p < .01; effect size [ES] ≤ 0.14), 1.82% decline in 5-m sled towing (p < .05; ES = 0.18), and 2.68% decline in 20-m sled towing (p < .01; ES = 0.27) between pre- and post-SSG. As in physical performance results, significant differences were observed between pre and post in physiological markers, with increasing tympanic temperature (36.21 ± 0.60 °C to 36.97 ± 0.59 °C; p < .001; ES = 1.27) and blood lactate concentrations (1.95 ± 1.30 mmol/L to 5.84 ± 2.04 mmol/L; p < .001; ES = 2.99) after SSG. The SSG produced a decrease in sprint and sled towing performance after 16 min of intense exercise. Moreover, the decrease in physical performance was accompanied with an increase in physiological responses. These neuromuscular responses could be similar in the real game; thus, coaching staff could benefit from this information when changing bench players.
Altered homeostasis and development of regulatory T cell subsets represent an IL-2R–dependent risk for diabetes in NOD mice
Authors: Dwyer Connor J. , Bayer Allison L. , Fotino Carmen , Yu Liping , Cabello-Kindelan Cecilia , Ward Natasha C. , Toomer Kevin H. , Chen Zhibin , Malek Thomas R.
Published: December 2017

Reducing IL-2 signaling in T cells results in accelerated diabetes in mice due to defective regulatory T cell function.
Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015
Authors: Castanheira Mariana , Duncan Leonard R. , Mendes Rodrigo E. , Sader Helio S. , Shortridge Dee
Published: December 2017

The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576
Pseudomonas aeruginosa
and 2,362
Enterobacteriaceae
isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the
P. aeruginosa
isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal β-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other β-lactams evaluated against
P. aeruginosa
groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the
Enterobacteriaceae
, being less active than only meropenem (95.6% susceptible) among the β-lactams evaluated. Against 145
Escherichia coli
and
Klebsiella pneumoniae
isolates carrying extended-spectrum-β-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly
bla
CTX-M-15
-like (89 isolates) and
bla
CTX-M-14
-like (22) genes but also
bla
SHV
(31) and
bla
TEM
(3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All β-lactams displayed limited activity against
bla
KPC
-carrying isolates. Ceftolozane-tazobactam was the most active β-lactam tested against
P. aeruginosa
isolates from isolates that were the probable cause of pneumonia and displayed
in vitro
activity against
Enterobacteriaceae
, including isolates resistant to cephalosporins and carrying ESBL genes.
Intrapulmonary Pharmacokinetics of Levonadifloxacin following Oral Administration of Alalevonadifloxacin to Healthy Adult Subjects
Authors: Rodvold Keith A. , Gotfried Mark H. , Chugh Rakesh , Gupta Mugdha , Yeole Ravindra , Patel Anasuya , Bhatia Ashima
Published: December 2017

Alalevonadifloxacin (WCK 2349) is a novell-alanine ester prodrug of levonadifloxacin that is being developed as an oral fluoroquinolone antibiotic. The primary objective of this study was to determine and compare plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levonadifloxacin following oral administration of alalevonadifloxacin to healthy adult subjects. Levonadifloxacin concentrations in plasma, ELF, and AM samples from 30 healthy subjects were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following oral dosing of alalevonadifloxacin (1,000 mg twice daily for 5 days). Six subjects were assigned to each bronchoalveolar lavage (BAL) fluid sampling time, i.e., 2, 4, 6, 8, or 12 h after the ninth oral dose. Noncompartmental pharmacokinetic (PK) parameters were determined from serial total plasma concentrations collected over a 12-h interval following the first and ninth oral doses. Penetration ratios were calculated from the areas under the concentration-time curves from 0 to 12 h (AUC0–12) for plasma, ELF, and AM by using mean (and median) concentrations at each BAL sampling time. Unbound plasma concentrations (∼85% plasma protein binding) were used to determine site-to-plasma penetration ratios. Plasma PK parameter values for levonadifloxacin were similar after the first and ninth doses. The respective AUC0–12values based on mean ELF and AM concentrations were 172.6 and 35.3 mg · h/liter, respectively. The penetration ratios for ELF and AM levonadifloxacin concentrations to unbound plasma levonadifloxacin concentrations were 7.66 and 1.58, respectively. Similar penetration ratios were observed with median concentrations. The observed plasma, ELF, and AM concentrations of levonadifloxacin support further studies of alalevonadifloxacin for treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT02253342.)
Human Cytomegalovirus Tegument Protein pp65 (pUL83) Dampens Type I Interferon Production by Inactivating the DNA Sensor cGAS without Affecting STING
Authors: Biolatti Matteo , Dell'Oste Valentina , Pautasso Sara , Gugliesi Francesca , von Einem Jens , Krapp Christian , Jakobsen Martin Roelsgaard , Borgogna Cinzia , Gariglio Marisa , De Andrea Marco , Landolfo Santo
Published: December 2017

The innate immune response plays a pivotal role during human cytomegalovirus (HCMV) primary infection. Indeed, HCMV infection of primary fibroblasts rapidly triggers strong induction of type I interferons (IFN-I), accompanied by proinflammatory cytokine release. Here, we show that primary human foreskin fibroblasts (HFFs) infected with a mutant HCMV TB40/E strain unable to express UL83-encoded pp65 (v65Stop) produce significantly higher IFN-β levels than HFFs infected with the wild-type TB40/E strain or the pp65 revertant (v65Rev), suggesting that the tegument protein pp65 may dampen IFN-β production. To clarify the mechanisms through which pp65 inhibits IFN-β production, we analyzed the activation of the cGAS/STING/IRF3 axis in HFFs infected with either the wild type, the revertant v65Rev, or the pp65-deficient mutant v65Stop. We found that pp65 selectively binds to cGAS and prevents its interaction with STING, thus inactivating the signaling pathway through the cGAS/STING/IRF3 axis. Consistently, addition of exogenous cGAMP to v65Rev-infected cells triggered the production of IFN-β levels similar to those observed with v65Stop-infected cells, confirming that pp65 inactivation of IFN-β production occurs at the cGAS level. Notably, within the first 24 h of HCMV infection, STING undergoes proteasome degradation independently of the presence or absence of pp65. Collectively, our data provide mechanistic insights into the interplay between HCMV pp65 and cGAS, leading to subsequent immune evasion by this prominent DNA virus.

IMPORTANCE
Primary human foreskin fibroblasts (HFFs) produce type I IFN (IFN-I) when infected with HCMV. However, we observed significantly higher IFN-β levels when HFFs were infected with HCMV that was unable to express UL83-encoded pp65 (v65Stop), suggesting that pp65 (pUL83) may constitute a viral evasion factor. This study demonstrates that the HCMV tegument protein pp65 inhibits IFN-β production by binding and inactivating cGAS early during infection. In addition, this inhibitory activity specifically targets cGAS, since it can be bypassed via the addition of exogenous cGAMP, even in the presence of pp65. Notably, STING proteasome-mediated degradation was observed in both the presence and absence of pp65. Collectively, our data underscore the important role of the tegument protein pp65 as a critical molecular hub in HCMV's evasion strategy against the innate immune response.
Emerging Alphaviruses Are Sensitive to Cellular States Induced by a Novel Small-Molecule Agonist of the STING Pathway
Authors: Gall Bryan , Pryke Kara , Abraham Jinu , Mizuno Nobuyo , Botto Sara , Sali Tina M. , Broeckel Rebecca , Haese Nicole , Nilsen Aaron , Placzek Andrew , Morrison Thomas , Heise Mark , Streblow Daniel , DeFilippis Victor
Published: December 2017

The type I interferon (IFN) system represents an essential innate immune response that renders cells resistant to virus growth via the molecular actions of IFN-induced effector proteins. IFN-mediated cellular states inhibit growth of numerous and diverse virus types, including those of known pathogenicity as well as potentially emerging agents. As such, targeted pharmacologic activation of the IFN response may represent a novel therapeutic strategy to prevent infection or spread of clinically impactful viruses. In light of this, we employed a high-throughput screen to identify small molecules capable of permeating the cell and of activating IFN-dependent signaling processes. Here we report the identification and characterization ofN-(methylcarbamoyl)-2-{[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}-2-phenylacetamide (referred to as C11), a novel compound capable of inducing IFN secretion from human cells. Using reverse genetics-based loss-of-function assays, we show that C11 activates the type I IFN response in a manner that requires the adaptor protein STING but not the alternative adaptors MAVS and TRIF. Importantly, treatment of cells with C11 generated a cellular state that potently blocked replication of multiple emerging alphavirus types, including chikungunya, Ross River, Venezuelan equine encephalitis, Mayaro, and O'nyong-nyong viruses. The antiviral effects of C11 were subsequently abrogated in cells lacking STING or the type I IFN receptor, indicating that they are mediated, at least predominantly, by way of STING-mediated IFN secretion and subsequent autocrine/paracrine signaling. This work also allowed characterization of differential antiviral roles of innate immune signaling adaptors and IFN-mediated responses and identified MAVS as being crucial to cellular resistance to alphavirus infection.

IMPORTANCEDue to the increase in emerging arthropod-borne viruses, such as chikungunya virus, that lack FDA-approved therapeutics and vaccines, it is important to better understand the signaling pathways that lead to clearance of virus. Here we show that C11 treatment makes human cells refractory to replication of a number of these viruses, which supports its value in increasing our understanding of the immune response and viral pathogenesis required to establish host infection. We also show that C11 depends on signaling through STING to produce antiviral type I interferon, which further supports its potential as a therapeutic drug or research tool.
Primary outcomes reporting in trials of paediatric type 1 diabetes mellitus: a systematic review
Authors: Khanpour Ardestani Samaneh , Karkhaneh Mohammad , Yu Hai Chuan , Hydrie Muhammad Zafar Iqbal , Vohra Sunita
Published: December 2017

Objective

Our objective was to systematically review randomised clinical trials (RCTs) of paediatric type 1 diabetes mellitus (T1DM) to assess reporting of (1) primary outcome, (2) outcome measurement properties and (3) presence or absence of adverse events.

Methods

Electronic searches in MEDLINE, EMBASE, CINAHL, Cochrane SR and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were undertaken. The search period was between 2001 and 2017. English-language RCTs on children younger than 21 years with T1DM were selected. We excluded studies of diagnostic or screening tools, multiple phase studies, protocols, and follow-up or secondary analysis of data.

Results

Of 11 816 unique references, 231 T1DM RCTs were included. Of total 231 included studies, 117 (50.6%) trials failed to report what their primary outcome was. Of 114 (49.4%) studies that reported primary outcome, 88 (77.2%) reported one and 26 (22.8%) more than one primary outcomes. Of 114 studies that clearly stated their primary outcome, 101 (88.6%) used biological/physiological measurements and 13 (11.4%) used instruments (eg, questionnaires, scales, etc) to measure their primary outcome; of these, 12 (92.3%) provided measurement properties or related citation. Of the 231 included studies, 105 (45.5%) reported that adverse events occurred, 39 (16.9%) reported that no adverse events were identified and 87 (37.7%) did not report on the presence or absence of adverse events.

Conclusion

Despite tremendous efforts to improve reporting of clinical trials, clear reporting of primary outcomes of RCTs for paediatric T1DM is still lacking. Adverse events due to DM interventions were often not reported in the included trials. Transparent reporting of primary outcome, validity of measurement tools and adverse events need to be improved in paediatric T1DM trials.
Evaluation of a federally funded mass media campaign and smoking cessation in pregnant women: a population-based study in three states
Authors: England Lucinda , Tong Van T , Rockhill Karilynn , Hsia Jason , McAfee Tim , Patel Deesha , Rupp Katelin , Conrey Elizabeth J , Valdivieso Claudia , Davis Kevin C
Published: December 2017

Objectives

In 2012, theCenters for Disease Control and Prevention initiated a national anti-smoking campaign,Tips from Former Smokers(Tips). As a result of the campaign, quit attempts among smokers increased in the general population by 3.7 percentage points. In the current study, we assessed the effects ofTipson smoking cessation in pregnant women.

Methods

We used 2009–2013 certificates of live births in three US states: Indiana, Kentucky and Ohio. Smoking cessation by the third trimester of pregnancy was examined among women who smoked in the 3 months prepregnancy. Campaign exposure was defined as overlap between the airing ofTips2012 (March 19–June 10) and the prepregnancy and pregnancy periods. Women who delivered beforeTips2012 were not exposed. Adjusted logistic regression was used to determine whether exposure toTipswas independently associated with smoking cessation.

Results

Cessation rates were stable during 2009–2011 but increased at the timeTips2012 aired and remained elevated. Overall, 32.9% of unexposed and 34.7% of exposed smokers quit by the third trimester (p<0.001). Exposure toTips2012 was associated with increased cessation (adjusted OR: 1.07, 95% CI 1.05 to 1.10).

Conclusions

Exposure to a national anti-smoking campaign for a general audience was associated with smoking cessation in pregnant women.
Frequency of equivocation in surgical meta-evidence: a review of systematic reviews within IBD literature
Authors: Delaney John D , Holbrook John T , Dewar Robert K , Laws Patrick J , Engel Alexander F
Published: December 2017

Objective

To assess the level of equivocation among level 1 evidence in ulcerative colitis and Crohn’s disease and determine whether any predisposing factors are present.

Method

MEDLINE, Embase, CINHAL and Cochrane were searched from 2006 to 2017. Papers were scored using AMSTAR and categorised into surgical (S), medical (M) or medical and surgical (MS) groups. The ability of each paper to make a recommendation and conclusiveness in doing so was recorded.

Results

278 papers were assessed. 82% (n=227) could make a recommendation, 18% (n=51) could not. There was a significant difference in ability to provide a recommendation between S and M (P=0.003) but not MS and M (P=0.022) nor S and MS (P=0.79). Where a recommendation was made, S papers were more likely to be tempered than M papers (P=0.014) but not MS papers (P=0.987).

Conclusions

Surgical meta-evidence within the inflammatory bowel disease domain is more than twice as likely as medical meta-evidence to be unable to provide a recommendation for clinical practice. Where a recommendation was made, surgical reviews were twice as likely to temper their conclusion.
Accrual monitoring in cardiovascular trials
Authors: Baldi Ileana , Gregori Dario , Desideri Alessandro , Berchialla Paola
Published: December 2017

Objective

To provide brief guidance on how to design accrual monitoring activities in a clinical trial protocol.

Setting

Two completed clinical trials that did not achieve the planned sample size, the Cost of Strategies After Myocardial Infarction (COSTAMI) trial and the Biventricular Pacing After Cardiac Surgery (BiPACS) trial.

Design

A Bayesian monitoring tool, the constant accrual model, is applied retrospectively to accrual data from each case study to illustrate how the tool could be used to identify problems with accrual early in the trial period and to frame the conditions in which the approach can be used in practice.

Results

After 312 days and 155 patients enrolled in the COSTAMI trial, accrual could be classified as ‘off target’ on the basis of statistical criteria outlined in the protocol. As for the BiPACS trial, after 2 years, it was already evident that the accrual was ‘considerably off target’.

Conclusions

Prompt awareness of a high risk of accrual failure could trigger different interventions to overcome protocol-related, patient-related or investigator-related barriers to recruitment or ultimately contribute to an early stopping decision due to recruitment futility.

Accrual prediction models should be included as standard tools for routine monitoring activities in cardiovascular research. Among them, methods relying on the Bayesian approach are particularly attractive, as they can naturally update past evidence when actual accrual data becomes available.
Epileptic seizure detection from EEG signals with phase–amplitude cross-frequency coupling and support vector machine
Authors: Liu Yang , Wang Jiang , Cai Lihui , Chen Yingyuan , Qin Yingmei
Published: December 2017

As a pattern of cross-frequency coupling (CFC), phase–amplitude coupling (PAC) depicts the interaction between the phase and amplitude of distinct frequency bands from the same signal, and has been proved to be closely related to the brain’s cognitive and memory activities. This work utilized PAC and support vector machine (SVM) classifier to identify the epileptic seizures from electroencephalogram (EEG) data. The entropy-based modulation index (MI) matrixes are used to express the strength of PAC, from which we extracted features as the input for classifier. Based on the Bonn database, which contains five datasets of EEG segments obtained from healthy volunteers and epileptic subjects, a 100% classification accuracy is achieved for identifying seizure ictal from healthy data, and an accuracy of 97.67% is reached in the classification of ictal EEG signals from inter-ictal EEGs. Based on the CHB–MIT database which is a group of continuously recorded epileptic EEGs by scalp electrodes, a 97.50% classification accuracy is obtained and a raising sign of MI value is found at 6[Formula: see text]s before seizure onset. The classification performance in this work is effective, and PAC can be considered as a useful tool for detecting and predicting the epileptic seizures and providing reference for clinical diagnosis.
A corrected model for static and dynamic electromechanical instability of narrow nanotweezers: Incorporation of size effect, surface layer and finite dimensions
Authors: Koochi Ali , Hosseini-Toudeshky Hossein , Abadyan Mohamadreza
Published: December 2017

Herein, a corrected theoretical model is proposed for modeling the static and dynamic behavior of electrostatically actuated narrow-width nanotweezers considering the correction due to finite dimensions, size dependency and surface energy. The Gurtin–Murdoch surface elasticity in conjunction with the modified couple stress theory is employed to consider the coupling effect of surface stresses and size phenomenon. In addition, the model accounts for the external force corrections by incorporating the impact of narrow width on the distribution of Casimir attraction, van der Waals (vdW) force and the fringing field effect. The proposed model is beneficial for the precise modeling of the narrow nanotweezers in nano-scale.
Hierarchical Solution of the Traveling Salesman Problem with Random Dyadic Tilings
Authors: Kalmár-Nagy Tamás , Bak Bendegúz Dezső
Published: December 2017

We propose a hierarchical heuristic approach for solving the Traveling Salesman Problem (TSP) in the unit square. The points are partitioned with a random dyadic tiling and clusters are formed by the points located in the same tile. Each cluster is represented by its geometrical barycenter and a “coarse” TSP solution is calculated for these barycenters. Midpoints are placed at the middle of each edge in the coarse solution. Near-optimal (or optimal) minimum tours are computed for each cluster. The tours are concatenated using the midpoints yielding a solution for the original TSP. The method is tested on random TSPs (independent, identically distributed points in the unit square) up to 10,000 points as well as on a popular benchmark problem (att532 — coordinates of 532 American cities). Our solutions are 8–13% longer than the optimal ones. We also present an optimization algorithm for the partitioning to improve our solutions. This algorithm further reduces the solution errors (by several percent using 1000 iteration steps). The numerical experiments demonstrate the viability of the approach.
METHODS FOR THE CHARACTERIZATION OF THE LONG-TERM MECHANICAL PERFORMANCE OF CEMENTS FOR VERTEBROPLASTY AND KYPHOPLASTY: CRITICAL REVIEW AND SUGGESTIONS FOR TEST METHODS
Authors: DANESI VALENTINA , FALDINI CESARE , CRISTOFOLINI LUCA
Published: December 2017

There is a growing interest towards bone cements for use in vertebroplasty and kyphoplasty, as such spine procedures are becoming more and more common. Such cements feature different compositions, including both traditional acrylic cements and resorbable and bioactive materials. Due to the different compositions and intended use, the mechanical requirements of cements for spinal applications differ from those of traditional cements used in joint replacement. Because of the great clinical implications, it is very important to assess their long-term mechanical competence in terms of fatigue strength and creep. This paper aims at offering a critical overview of the methods currently adopted for such mechanical tests. The existing international standards and guidelines and the literature were searched for publications relevant to fatigue and creep of cements for vertebroplasty and kyphoplasty. While standard methods are available for traditional bone cements in general, no standard indicates specific methods or acceptance criteria for fatigue and creep of cements for vertebroplasty and kyphoplasty. Similarly, a large number of papers were published on cements for joint replacements, but only few cover fatigue and creep of cements for vertebroplasty and kyphoplasty. Furthermore, the literature was analyzed to provide some indications of tests parameters and acceptance criteria (number of cycles, duration in time, stress levels, acceptable amount of creep) for possible tests specifically relevant to cements for spinal applications.
A Development of a SPH Model for Simulating Surface Erosion by Impact(s) of Irregularly Shaped Particles
Authors: Dong Xiangwei , Li Zengliang , Mao Zirui , Lin Tao
Published: December 2017

Modeling and studying the impact of angular particles are very helpful in understanding the fundamental mechanisms of erosive wear. However, the majority of previous studies focused on well-defined symmetrical particles, which are not well representative of the abrasive particles. Hence, this study develops a mesh-free model based on the smoothed particle hydrodynamics (SPH) method to simulate impact(s) of single and multiple irregularly shaped particles on ductile material. A novel procedure is proposed to model the particle as a polygonal rigid body through measuring the corner vertices. Simulations are carried out by varying the input conditions and by using different types of angular particles. Common erosion mechanisms such as cutting, machining, ploughing, prying-off are successfully reproduced by the model. The predicted crater is compared with available experimental data, and good agreement has been achieved. The proposed SPH model and out present study could be useful in the study of erosive wear on the surface of metal devices that carries granular substances.
Novel Genetic Variants of Hepatitis B Virus in Fulminant Hepatitis
Authors: Chook Jack Bee , Ngeow Yun Fong , Tee Kok Keng , Peh Suat Cheng , Mohamed Rosmawati
Published: December 2017

Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%), K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%). We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.
Unique Phrenic Nerve-Sparing Regional Anesthetic Technique for Pain Management after Shoulder Surgery
Authors: Panchamia Jason K. , Olsen David A. , Amundson Adam W.
Published: December 2017

Background. Ipsilateral phrenic nerve blockade is a common adverse event after an interscalene brachial plexus block, which can result in respiratory deterioration in patients with preexisting pulmonary conditions. Diaphragm-sparing nerve block techniques are continuing to evolve, with the intention of providing satisfactory postoperative analgesia while minimizing hemidiaphragmatic paralysis after shoulder surgery. Case Report. We report the successful application of a combined ultrasound-guided infraclavicular brachial plexus block and suprascapular nerve block in a patient with a complicated pulmonary history undergoing a total shoulder replacement. Conclusion. This case report briefly reviews the important innervations to the shoulder joint and examines the utility of the infraclavicular brachial plexus block for postoperative pain management.
Postpartum Vaginal Blood Loss following Two Different Methods of Cervical Ripening
Authors: Okon Okon Asuquo , Ekabua John Egede
Published: December 2017

Eighty women undergoing induction of labor at the University of Calabar Teaching Hospital were recruited and randomly allocated into two treatment groups (40 each), to receive either serial 50 µg doses of misoprostol or intracervical Foley catheter. Vaginal blood loss was collected and measured using an under buttocks plastic collection bag and by perineal pad weighing up to 6 hours postpartum. There were no significant differences between the two groups with respect to sociodemographic and obstetric characteristics. Comparison of blood loss in vaginal deliveries between the two groups revealed that subjects in the misoprostol group had significantly higher blood loss than subjects in the Foley catheter group (488 ± 222 versus 326 ± 106, p<0.05). In both groups, there was strong and statistically significant positive correlation between postpartum blood loss and induction delivery interval (r=0.75, p<0.0001; r=0.77, p<0.0001). There were no significant differences in maternal outcomes. In view of this, further study is required to ascertain if lower doses of misoprostol for induction of labor may result in lesser blood loss. This trial is registered with ISRCTN14479515.
NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib
Authors: Kankia Ibrahim H. , Khalil Hilal S. , Langdon Simon P. , Moult Peter R. , Bown James L. , Deeni Yusuf Y.
Published: December 2017

NF‐E2‐related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy.
In Vitro Anthelmintic Activity of Crude Extracts of Aerial Parts of Cissus quadrangularis L. and Leaves of Schinus molle L. against Haemonchus contortus
Authors: Zenebe Selamawit , Feyera Teka , Assefa Solomon
Published: December 2017

Background. Haemonchus contortus, the causative agent of Haemonchosis, is the most economically important parasite in small ruminant production. Control with chemotherapy has not been successful due to rapid emergence of drug-resistant strains. There is a continuous search for alternative leads particularly from plants. The study aimed to evaluate the anthelmintic activity of crude methanolic extracts of leaves of Schinus molle and aerial parts of Cissus quadrangularis against H. contortus. Methods. Adult motility test and egg hatching inhibition assay were employed to investigate the in vitro adulticidal and egg hatching inhibitory effects of the extracts. Results. Higher concentrations of the extracts (10 and 5 mg/ml) had a significantly superior adulticidal activity (p<0.05) compared to the negative control and lower concentration levels, which was comparable to albendazole. Similarly, the relative egg hatch inhibition efficacy of S. molle and C. quadrangularis extracts indicated a maximum of 96% and 88% egg hatch inhibition, respectively, within the 48 hrs of exposure at 1 mg/ml. Conclusion. The current study evidenced that the crude methanolic extracts of the plants have promising adulticidal and egg hatching inhibitory effects against H. contortus.