bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with loss to follow‐up in women undergoing repair for obstetric fistula in Guinea
Authors: Delamou Alexandre , Delvaux Thérèse , Utz Bettina , Camara Bienvenu Salim , Beavogui Abdoul Habib , Cole Bethany , Levin Karen , Diallo Moustapha , Millimono Sita , Barry Thierno Hamido , El Ayadi Alison Marie , Zhang Wei‐Hong , De Brouwere Vincent
Published: August 2015

Objectives

To analyse the trend of loss to follow‐up over time and identify factors associated with women being lost to follow‐up after discharge in three fistula repair hospitals in Guinea.

Methods

This retrospective cohort study used data extracted from medical records of fistula repairs conducted from 1 January 2007 to 30 September 2013. A woman was considered lost to follow‐up if she did not return within 4 months post‐discharge. Factors associated with loss to follow‐up were identified using a subsample of the data covering the period 2010–2013.

Results

Over the study period, the proportion of loss to follow‐up was 21.5% (448/2080) and varied across repair hospitals and over time with an increase from 2% in 2009 to 52% in 2013. After adjusting for other variables in a multivariate logistic regression model, women who underwent surgery at Labe hospital and at Kissidougou hospital were more likely to be lost to follow‐up than women operated at Jean Paul II hospital (OR: 50.6; 95% CI: 24.9–102.8) and (OR: 11.5; 95% CI: 6.1–22.0), respectively. Women with their fistula closed at hospital discharge (OR: 3.2; 95% CI: 2.1–4.8) and women admitted for repair in years 2011–2013 showed higher loss to follow‐up as compared to 2010. Finally, loss to follow‐up increased by 2‰ for each additional kilometre of distance a client lived from the repair hospital (OR: 1.002; 95% CI: 1.001–1.003).

Conclusion

Reimbursement of transport was the likely reason for change over time of LTFU. Reducing geographical barriers to care for women with fistula could sustain fistula care positive outcomes.
A novel GYPB‐A‐B hybrid gene responsible for Ss and MN typing discrepancies
Authors: Willemetz Alexandra , Nataf Joelle , Peyrard Thierry , Arnaud Lionel
Published: August 2015

BACKGROUND

Transfusion support of S–s– patients is very challenging but can now be alleviated by genotyping mutations in the GYPB gene to predict their U– or U+var phenotype. However, the phenotype predicted by genotyping does not always correspond to the observed phenotype of red blood cells (RBCs), which requires further investigation to avoid such a typing discrepancy in the future. In this study, we elucidated the case of an S–s– female patient of African origin who was predicted to be S+s– by our genotyping platform.

STUDY DESIGN AND METHODS

Long‐range polymerase chain reaction (PCR) amplification and extended Sanger sequencing were required.

RESULTS

The Ss typing discrepancy in the proband resulted from a converted GYPB allele that encodes neither S nor s due to the replacement of Exon B4 of GYPB by the homologous Exon A4 of GYPA. In this novel GYPB‐A‐B hybrid gene, the GYPA segment actually starts just downstream of Exon B2, causing a MN typing discrepancy too. While the proband's RBCs were M+N–, the genotyping predicted the M+N+ phenotype.

CONCLUSION

The reported GYPB‐A‐B hybrid gene constitutes a limitation for the accurate prediction of the MN and Ss phenotypes by current genotyping methods. A PCR assay was therefore developed to detect its presence.
Diagnosis and Surgical Management of Congenital Laxity of the Fibularis Musculotendinous Unit Resulting in Hyperextension of the Tarsus in 14 Calves
Authors: Kilic Engin , Ozaydin Isa , Aksoy Ozgur , Yayla Sadik
Published: August 2015

Objective

To describe the diagnosis and surgical management of congenital laxity of the fibularis tendon resulting in hyperextension of the tarsus in calves.

Study Design

Case series.

Animals

Fourteen calves (3 unilateral, 11 bilateral) diagnosed with congenital tarsal instability caused by laxity of the fibularis musculotendinous unit resulting in hyperextension of the tarsus.

Methods

Diagnosis was made by clinical and radiologic assessments. The tarsus was surgically prepared and an incision made on the dorsal surface of the tarsus after intrathecal anesthesia with the calf sedated. A locking‐loop suture (4 loops) was applied to the fibularis tendon using polyglactin 910. The free ends of the suture were then tied to the shank of a cortical bone screw inserted in the proximal metatarsus.

Results

The calves were evaluated on postoperative days 15, 30, and 60 and were walking normally.

Conclusion

Congenital tarsal instability because of laxity of the fibularis musculotendoninous unit is described and surgical treatment directed at shortening the tendon shows promising results.
Sentence‐final adverbs in Singapore English and Hong Kong English
Authors: HIRAMOTO MIE
Published: August 2015

Available corpus data show that adverbs with modifying meanings,already,also, andonly, occur at the clause‐final or sentence‐final position more often in ‘Asian Englishes’ (Hong Kong English and Singapore English) than British English and Canadian English. This paper posits a link between the motivation of sentence‐final adverbs in Asian English and substrate transfer due to linguistic (both grammatical and pragmatic) structures of influential non‐English languages in the regions.
Formal Fourier Jacobi expansions and special cycles of codimension two
Authors: Westerholt-Raum Martin
Published: August 2015

We prove that formal Fourier Jacobi expansions of degree two are Siegel modular forms. As a corollary, we deduce modularity of the generating function of special cycles of codimension two, which were defined by Kudla. A second application is the proof of termination of an algorithm to compute Fourier expansions of arbitrary Siegel modular forms of degree two. Combining both results enables us to determine relations of special cycles in the second Chow group.
Characterization of Emissions From the Use of Alternative Aviation Fuels
Authors: Chan Tak W. , Chishty Wajid A. , Canteenwalla Pervez , Buote David , Davison Craig R.
Published: August 2015

Alternative fuels for aviation are now a reality. These fuels not only reduce reliance on conventional petroleum-based fuels as the primary propulsion source, but also offer promise for environmental sustainability. While these alternative fuels meet the aviation fuels standards and their overall properties resemble those of the conventional fuel, they are expected to demonstrate different exhaust emissions characteristics because of the inherent variations in their chemical composition resulting from the variations involved in the processing of these fuels. This paper presents the results of back-to-back comparison of emissions characterization tests that were performed using three alternative aviation fuels in a GE CF-700-2D-2 engine core. The fuels used were an unblended synthetic kerosene fuel with aromatics (SKA), an unblended Fischer–Tropsch (FT) synthetic paraffinic kerosene (SPK) and a semisynthetic 50–50 blend of Jet A-1 and hydroprocessed SPK. Results indicate that while there is little dissimilarity in the gaseous emissions profiles from these alternative fuels, there is however a significant difference in the particulate matter emissions from these fuels. These differences are primarily attributed to the variations in the aromatic and hydrogen contents in the fuels with some contributions from the hydrogen-to-carbon ratio of the fuels.
Experimental Investigation of the Transition Mechanism From Stable Flame to Flashback in a Generic Premixed Combustion System With High-Speed Micro-Particle Image Velocimetry and Micro-PLIF Combined With Chemiluminescence Imaging
Authors: Baumgartner Georg , Boeck Lorenz R. , Sattelmayer Thomas
Published: August 2015

Sustainable power generation resulting in low pollutant emissions, such as CO2 and NOx, poses a very challenging task in the near future. Premixed combustion of hydrogen-rich fuels in gas turbines is a promising approach to cope with ever more stringent regulations on emission levels. This method, however, involves the risk of flame flashback from the desired flame position into the premixing section, leading to catastrophic failure of the machine components that are not designed for such high temperatures. The objective of the current study was to visualize and describe the transition from stable flame to flashback in a generic H2–air combustion system and develop a physics-based model for the description of the transition. In order to achieve the high temporal and spatial resolution required for capturing the involved effects, high-speed particle image velocimetry (PIV) and high-speed planar laser-induced fluorescence (PLIF) were employed. In order to characterize the interaction of the flame with the flow in detail, both measurement techniques were applied to very small fields-of-view using (UV) long-distance microscopes. The repetition rates were 20 kHz for PLIF and 3 kHz for PIV, respectively. During both the PLIF and the PIV measurements, the flame's OH*-chemiluminescence was captured from a perspective perpendicular to that of the PLIF/PIV camera for further flame characterization. The microscopic measurements revealed that there is a negligible influence of the unconfined flame on the incoming burner flow in stable mode. Upon approaching the flashback conditions, however, the velocity profile of the burner flow is distinctly distorted by the presence of the flame inside the premixing duct. The flow directly upstream of the flame is retarded and deflected around the leading flame tip. Based on the effects observed in the experiments, a new flashback model is proposed, which identifies the heat transfer to the burner rim and the flame speed as the main drivers for the onset of flashback, whereas the flame backpressure is the governing factor for the subsequent upstream flame propagation.
Drag Reduction in Synthetic Seawater by Flexible and Rigid Polymer Addition Into a Rotating Cylindrical Double Gap Device
Authors: Andrade Rafhael M. , Pereira Anselmo S. , Soares Edson J.
Published: August 2015

Flexible and rigid long chain polymers in very dilute solutions can significantly reduce the drag in turbulent flows. The polymers successively stretch and coil by interacting with the turbulent structures, which changes the turbulent flow and further imposes a transient behavior on the drag reduction (DR) as well as a subsequent mechanical polymer degradation. This time-dependent phenomenon is strongly affected by a number of parameters, which are analyzed here, such as the Reynolds number, polymer concentration, polymer molecular weight, and salt concentration. This last parameter can dramatically modify the polymeric structure. The investigation of the salt concentration's impact on the DR is mostly motivated by some potential applications of this technique to ocean transport and saline fluid flows. In the present paper, a cylindrical double gap rheometer device is used to study the effects of salt concentration on DR over time. The reduction of drag is induced by three polymers: poly (ethylene oxide) (PEO), polyacrylamide (PAM), and xanthan gum (XG). These polymers are dissolved in deionized water both in the presence of salt and in its absence. The DR is displayed from the very start of the test to the time when the DR achieves its final level of efficiency, following the mechanical degradations. The presence of salt in PEO and XG solutions reduces the maximum DR, DRmax, as well as the time to achieve it. In contrast, the DR does not significantly change over the time for PAM solutions upon the addition of salt.
Multimaterial and Multiscale Three-Dimensional Bioprinter
Authors: Campbell Jennifer , McGuinness Ian , Wirz Holger , Sharon Andre , Sauer-Budge Alexis F.
Published: August 2015

We have developed a three-dimensional (3D) bioprinting system capable of multimaterial and multiscale deposition to enable the next generation of “bottom-up” tissue engineering. This area of research resides at the interface of engineering and life sciences. As such, it entails the design and implementation of diverse elements: a novel hydrogel-based bioink, a 3D bioprinter, automation software, and mammalian cell culture. Our bioprinter has three components uniquely combined into a comprehensive tool: syringe pumps connected to a selector valve that allow precise application of up to five different materials with varying viscosities and chemistries, a high velocity/high-precision x–y–z stage to accommodate the most rapid speeds allowable by the printed materials, and temperature control of the bioink reservoirs, lines, and printing environment. Our custom-designed bioprinter is able to print multiple materials (or multiple cell types in the same material) concurrently with various feature sizes (100 μm–1 mm wide; 100 μm–1 cm high). One of these materials is a biocompatible, printable bioink that has been used to test for cell survival within the hydrogel following printing. Hand-printed (HP) controls show that our bioprinter does not adversely affect the viability of the printed cells. Here, we report the design and build of the 3D bioprinter, the optimization of the bioink, and the stability and viability of our printed constructs.
Influence of Carbon Nanotubes on Conductive Capacity and Tribological Characteristics of Poly(ethylene Glycol-Ran-Propylene Glycol) Monobutyl Ether as Base Oil of Grease
Authors: Ge Xiangyu , Xia Yanqiu , Feng Xin
Published: August 2015

Carbon black (CB) and three kinds of carbon nanotubes (CNTs) including multiwalled CNTs (MWCNTs), carboxyl multiwalled CNTs (CMWCNTs), and single-walled CNTs (SWCNTs) were doped as conductive additives in poly(ethylene glycol-ran-propylene glycol) monobutyl ether (denoted as PAG) to afford conductive greases in the presence of polytetrafluoroethylene (PTFE) as the thickener and acetone as the polar dispersant. The effects of the conductive additives on the conductive capacity and tribological characteristics of the PAG grease were investigated, and the tribological action mechanisms of the conductive additives were analyzed in relation to worn surface analyses by scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). Results indicate that the SWCNTs can reduce the volume resistivity of the base grease by over 10,000 times. In the meantime, the CB and the three kinds of CNTs as conductive additives can improve the tribological characteristics of the base grease to some extent, and the CNTs are advantageous over the CB in improving the friction-reducing and antiwear abilities of the base grease. The reason lies in that CNTs with a small size and a large specific surface area can be easily adsorbed on sliding steel surfaces to form a surface protective film.
Failure Mode and Fatigue Behavior of Dissimilar Friction Stir Spot Welds in Lap-Shear Specimens of Transformation-Induced Plasticity Steel and Hot-Stamped Boron Steel Sheets
Authors: Hong S. H. , Sung S.-J. , Pan J.
Published: August 2015

Failure mode and fatigue behavior of dissimilar friction stir spot welds in lap-shear specimens of transformation-induced plasticity steel (TRIP780) and hot-stamped boron steel (HSBS) sheets are examined in this paper. Optical micrographs of the dissimilar TRIP780/HSBS friction stir spot welds made by a concave silicon nitride tool before and after testing are obtained and examined. These micrographs indicate that subject to quasi-static and cyclic loading conditions, the TRIP780/HSBS welds fail from cracks growing through the TRIP780 sheets where the tool was plunged into and the thickness was reduced. The bending moments and the transverse shear force near the welds are derived with consideration of the load offset, the weld gap, and the bend distance for calculation of analytical global stress intensity factor solutions for the welds in lap-shear specimens. A fatigue model of kinked crack growth is used to estimate fatigue lives based on the local stress intensity factor solutions for kinked cracks. The estimated fatigue lives with consideration of the weld gap and the bend distance are in agreement with the fatigue test results under low-cycle loading conditions and lower than the fatigue test results under high-cycle loading conditions. The estimated fatigue lives suggest that the weld gap and the bend distance can significantly affect fatigue lives of the friction stir spot welds in lap-shear specimens under cyclic loading conditions.
Structural and Rotordynamic Force Coefficients of a Shimmed Bump Foil Bearing: An Assessment of a Simple Engineering Practice
Authors: San Andrés Luis , Norsworthy Joshua
Published: August 2015

High speed rotors supported on bump-type foil bearings (BFBs) often suffer from large subsynchronous whirl motions. Mechanically preloading BFBs through shimming is a common, low cost practice that shows improvements in rotordynamic stability. However, there is an absence of empirical information related to the force coefficients (structural and rotordynamic) of shimmed BFBs. This paper details a concerted study toward assessing the effect of shimming on a first generation BFB (L = 38.1 mm and D = 36.5 mm). Three metal shims, 120 deg apart, are glued to the inner surface of the bearing cartridge and facing the underside of the bump foil strip. The shim sets are of identical thickness, either 30 μm or 50 μm. In static load tests, a bearing with shims shows a (nonlinear) structural stiffness larger than for the bearing without shims. Torque measurements during shaft acceleration also demonstrate a shimmed BFB has a larger friction coefficient. For a static load of 14.3 kPa, dynamic loads with a frequency sweep from 250 Hz to 450 Hz are exerted on the BFB, without and with shims, to estimate its rotordynamic force coefficients while operating at ∼50 krpm (833 Hz). Similar measurements are conducted without shaft rotation. Results are presented for the original BFB (without shims) and the two shimmed BFB configurations. The direct stiffnesses of the BFB, shimmed or not, increase with excitation frequency, thus evidencing a mild hardening effect. The BFB stiffness and damping coefficients decrease slightly for operation with rotor speed as opposed to the coefficients when the shaft is stationary. For frequencies above 300 Hz, the direct damping coefficients of the BFB with 50 μm thick shims are ∼30% larger than the coefficients of the original bearing. The bearing structural loss factor, a measure of its ability to dissipate mechanical energy, is derived from the direct stiffness and damping coefficients. The BFB with 50 μm thick shims has a 25% larger loss factor—average from test data collected at 300 Hz to 400 Hz—than the original BFB. Further measurements of rotor motions while the shaft accelerates to ∼50 krpm demonstrate the shimmed BFB (thickest shim set) effectively removes subsynchronous whirl motions amplitudes that were conspicuous when operating with the original bearing.
Technical Note: MTF determination from a star bar pattern image
Authors: González‐López Antonio , Ruiz‐Morales Carmen
Published: August 2015

Purpose:

A procedure to obtain the MTF of an image system from a star bar pattern image is presented. The results obtained are compared to the standard analysis of an edge image (as described in the norm IEC 62220‐1).

Methods:

The images used are artificially generated following a procedure that simulates sampling, blurring, and noise present in a real phantom image. The MTF from a star bar pattern is obtained from the analysis of circular scans over the star pattern image and concentric to it. The radius of the scanning circumference is proportional to the spatial frequency of the curve arising from the scan, and the amplitude of this curve is directly related to the system MTF for that frequency. An oversampling procedure is also followed to minimize the effect of noise in the image. In order to investigate the MTF in a particular direction, the image analysis is restricted to an angular sector centered around that direction.

Results:

The MTFs calculated following this procedure show a very good agreement with those obtained following the standard IEC 62220‐1 for low noise levels. As the noise increases, however, the star bar method is more accurate than the edge method.

Conclusions:

The procedure presented provides a good method to investigate the MTF in any spatial direction. Finally, as the whole star bar pattern image is used for MTF computation, the high signal to noise ratio guarantees a good immunity against noise.
Quadrupedal Locomotion–Respiration Entrainment and Metabolic Economy in Cross-Country Skiers
Authors: Boldt Kevin , Killick Anthony , Herzog Walter
Published: August 2015

A 1:1 locomotion–respiration entrainment is observed in galloping quadrupeds, and is thought to improve running economy. However, this has not been tested directly in animals, as animals cannot voluntarily disrupt this entrainment. The purpose of this study was to evaluate metabolic economy in a human gait involving all four limbs, cross-country skiing, in natural entrainment and forced nonentrainment. Nine elite cross-country skiers roller skied at constant speed using the 2-skate technique. In the first and last conditions, athletes used the natural entrained breathing pattern: inhaling with arm recovery and exhaling with arm propulsion, and in the second condition, the athletes disentrained their breathing pattern. The rate of oxygen uptake (VO2) and metabolic rate (MR) were measured via expired gas analysis. Propulsive forces were measured with instrumented skis and poles. VO2 and MR increased by 4% and 5% respectively when skiers used the disentrained compared with the entrained breathing pattern. There were no differences in ski or pole forces or in timing of the gait cycle between conditions. We conclude that breathing entrainment reduces metabolic cost of cross-country skiing by approximately 4%. Further, this reduction is likely a result of the entrainment rather than alterations in gait mechanics.
A Comparison of Gluteus Maximus, Biceps Femoris, and Vastus Lateralis Electromyography Amplitude in the Parallel, Full, and Front Squat Variations in Resistance-Trained Females
Authors: Contreras Bret , Vigotsky Andrew D. , Schoenfeld Brad J. , Beardsley Chris , Cronin John
Published: August 2015

Front, full, and parallel squats are some of the most popular squat variations. The purpose of this investigation was to compare mean and peak electromyography (EMG) amplitude of the upper gluteus maximus, lower gluteus maximus, biceps femoris, and vastus lateralis of front, full, and parallel squats. Thirteen healthy women (age = 28.9 ± 5.1 y; height = 164 ± 6.3 cm; body mass = 58.2 ± 6.4 kg) performed 10 repetitions of their estimated 10-repetition maximum of each respective variation. There were no statistical (P = .05) differences between full, front, and parallel squats in any of the tested muscles. Given these findings, it can be concluded that the front, full, or parallel squat can be performed for similar EMG amplitudes. However, given the results of previous research, it is recommended that individuals use a full range of motion when squatting, assuming full range can be safely achieved, to promote more favorable training adaptations. Furthermore, despite requiring lighter loads, the front squat may provide a similar training stimulus to the back squat.
Independent Associations of Organized Physical Activity and Weight Status with Children’s Cognitive Functioning: A Matched-Pairs Design
Authors: Davis Catherine L. , Tkacz Joseph P. , Tomporowski Phillip D. , Bustamante Eduardo E.
Published: August 2015

Purpose:

This study tested whether participation in organized physical activity (active vs. inactive) or weight status (normal weight vs. overweight or obese) independently relate to children’s cognition, using a matched-pairs design.

Design and Methods:

Normal weight, active children (8–11 yrs, 5th-75th percentile BMI) were recruited from extracurricular physical activity programs while normal weight inactive (5th-75th percentile BMI) and overweight inactive children (BMI ≥85th percentile) were recruited from local Augusta, Georgia area schools. Measures included the Cognitive Assessment System, anthropometrics, and parent- and self-report of physical activity. Paired t tests compared cognition scores between matched groups of normal weight active vs. normal weight inactive (N = 24 pairs), normal weight inactive vs. overweight inactive (N = 21 pairs), and normal weight active vs. overweight inactive children (N = 16 pairs). Children in each comparison were matched for race, gender, age, and socioeconomic status.

Results:

Normal weight active children had higher Planning (M± SD = 109 ± 11 vs. 100 ± 11, p = .011) and Attention scores (108 ± 11 vs. 100 ± 11, p = .013) than overweight inactive children. Normal weight inactive children had higher Attention scores than overweight inactive children (105 ± 13 vs. 93 ± 12, p = .008). When compared with normal weight inactive children, normal weight active children had higher Planning (113 ± 10 vs. 102 ± 13, p = .008) and marginally higher Attention scores (111 ± 11 vs. 104 ± 12, p = .06).

Conclusion:

Findings suggest independent associations of children’s weight status with selective attention, and physical activity with higher-order processes of executive function.
The Acute Effects of Supramaximal High-Intensity Intermittent Exercise on Vascular Function in Lean vs. Obese Prepubescent Boys
Authors: Chuensiri Napasakorn , Tanaka Hirofumi , Suksom Daroonwan
Published: August 2015

Purpose:

To determine the acute effects of high-intensity intermittent exercise (HIIE) on vascular function.

Methods:

Lean (n = 18, BMI = 17.1 ± 0.7) and obese (n = 17, BMI = 25.4 ± 0.8) prepubescent boys aged 10.2 ± 0.2 years were studied. HIIE consisted of 8 sets of 20 s of cycle ergometry at 100, 130, and 170% of VO2peak alternating with 10 s of rests.

Results:

The obese group had higher (p < .05) body mass, BMI, body fat percentage, waist-hip ratio than the lean group. Carotid artery wall thickness and arterial stiffness as assessed by brachial-ankle pulse wave velocity (baPWV) were greater in the obese than in the lean group (p < .05). Brachial artery flow-mediated dilation (FMD) was not different between the groups. Total energy expenditure increased gradually as the exercise intensity increased in both groups (p < .05). The obese group had significantly greater total energy expenditure in all three HIIE intensities than the lean group. FMD tended to be higher and baPWV lower as the exercise intensity increased in both groups. Only the HIIE at 170% demonstrated greater FMD compared with the baseline in both groups. baPWV decreased significantly after HIIE at 130 and 170% VO2peak in both groups.

Conclusion:

Supramaximal HIIE can be a feasible exercise modality for improving vascular function in obese prepubescent boys. Future exercise intervention studies are warranted.
Unusual Ebola vaccine study pays off in Guinea
Authors: Enserink Martin
Published: August 2015

A vaccination trial targeting contacts of cases produces landmark results.
Monarchs pose a puzzle
Authors: DeMarco Emily
Published: August 2015

Mexico's sharp winter declines not apparent in summer surveys elsewhere.
Catching cosmic rays where they live
Authors: Conover Emily
Published: August 2015

The International Space Station gears up to study high-energy particles in space.
Don't mess with the bears
Authors: Kintisch Eli
Published: August 2015

With sea ice receding polar bears may be venturing more on land, creating new risks for scientists.
TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD
Authors: Ling Jonathan P. , Pletnikova Olga , Troncoso Juan C. , Wong Philip C.
Published: August 2015

Mechanistic surprise in ALS-FTD

Intense efforts have focused on identifying therapeutic targets for misfolded proteins that cause amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). Ling
et al.
show that the main culprit of proteinopathy, TDP-43, acts as a splicing suppressor of nonconserved cryptic exons. These exons often disrupt messenger RNA translation and promote nonsense-mediated decay. When TDP-43 was depleted in cells, a set of nonconserved cryptic exons spliced into target RNAs, leading to down-regulation of corresponding proteins critical for cellular function. Repression of cryptic exons prevented cell death in TDP-43–null cells. Because brains of ALS-FTD cases showed evidence of missplicing of cryptic exons, failure in these regions may underlie TDP-43 proteinopathy.

Science
, this issue p.
650
Clinical and Analytical Performance of the Onclarity HPV Assay Using the VALGENT Framework
Authors: Cuschieri K. , Geraets D. T. , Moore C. , Quint W. , Duvall E. , Arbyn M.
Published: August 2015

As the demand for human papillomavirus (HPV)-related cervical screening increases, emerging HPV tests must be evaluated robustly using well-annotated samples, such as those generated in the Validation of HPV Genotyping Tests (VALGENT) framework. Through VALGENT, we assessed the performance of the BD Onclarity HPV assay, which detects 14 high-risk (HR) types and resolves six individual types and three groups of types. Consecutive samples from a screening population (n= 1,000), enriched with cytologically abnormal samples (n= 300), that had been tested previously with the GP5+/6+ PCR enzyme immunoassay (EIA) and the GP5+/6+ PCR LMNX assay (Diassay) were tested with the Onclarity assay. Type-specific HPV prevalences were analyzed according to age and cytological result. The accuracy of the Onclarity assay for the detection of cervical intraepithelial neoplasia grade 2+ (CIN2+) and CIN3+ was assessed relative to the GP5+/6+ EIA results by using noninferiority criteria. Overall agreement and type-specific agreement between the Onclarity assay and the GP5+/6+ LMNX assay were assessed. The prevalence of HPV types 16, 18, 31, and 45 increased with the severity of cytological results (Pfor trend, <0.05). For the detection of CIN2+, the Onclarity assay had a relative sensitivity of 1.02 (95% confidence interval [CI], 0.99 to 1.05;P< 0.001 for noninferiority) and a relative specificity of 0.99 (95% CI, 0.97 to 1.00;P= 0.186 for noninferiority). The kappa for agreement between the Onclarity assay and the GP5+/6+ LMNX assay for HR-HPV was 0.92 (95% CI, 0.89 to 0.94), and values for the six individual types ranged from 0.78 (95% CI, 0.68 to 0.87) for HPV-52 to 0.96 (95% CI, 0.93 to 0.99) for HPV-16. These data suggest that the Onclarity assay offers applications for clinical workstreams while providing genotyping information that may be useful for risk stratification beyond types 16 and 18.
Human Cytotoxic T Lymphocyte-Mediated Acute Liver Failure and Rescue by Immunoglobulin in Human Hepatocyte Transplant TK-NOG Mice
Authors: Uchida Takuro , Hiraga Nobuhiko , Imamura Michio , Tsuge Masataka , Abe Hiromi , Hayes C. Nelson , Aikata Hiroshi , Ishida Yuji , Tateno Chise , Yoshizato Katsutoshi , Ohdan Hideki , Murakami Kazunari , Chayama Kazuaki
Published: August 2015

Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are critical in eliminating infection. We developed an animal model in which HBV-infected human hepatocytes are targeted by HBV-specific CTLs. After HBV inoculation in human hepatocyte-transplanted herpes simplex virus type-1 thymidine kinase-NOG mice, human peripheral blood mononuclear cells (PBMCs) were administered, and albumin, HBV DNA, alanine aminotransferase (ALT), and cytokine levels were analyzed. Histopathological and flow-cytometric analysis of infiltrating human immune cells were performed, and the efficacy of CTL-associated antigen-4 immunoglobulin (CTLA4Ig) against liver damage was evaluated. PBMC treatment resulted in massive hepatocyte damage with elevation of ALT, granzyme A, and gamma interferon and decrease in albumin and HBV DNA. The number of liver-infiltrating human lymphocytes and CD8-positive cells was significantly higher in HBV-infected mice. HBV-specific CTLs were detected by core and polymerase peptide-major histocompatibility complex-tetramer, and the population of regulatory T cells was significantly decreased in HBV-infected mice. Serum hepatitis B surface (HBs) antigen became negative, and HBs antibody appeared. CTLA4Ig treatment strongly inhibited infiltration of mononuclear cells. CTLA4Ig treatment will be used to treat patients who develop severe acute hepatitis B to prevent liver transplantation or lethality. This animal model is useful for virological and immunological analysis of HBV infection and to develop new therapies for severe acute hepatitis B.

IMPORTANCEWithout liver transplantation, some HBV-infected patients will die from severe liver damage due to acute overreaction of the immune system. No effective treatment exists, due in part to the lack of a suitable animal model. An animal model is necessary to investigate the mechanism of hepatitis and to develop therapeutic strategies to prevent acute liver failure in HBV infection. We developed an animal model in which HBV-infected human hepatocytes are targeted by human HBV-specific CTLs. In this model, HBV-infected human hepatocytes were transplanted into severely immunodeficient NOG mice in order to reconstruct elements of the human immune system. Using this model, we found that CTL-associated antigen-4 immunoglobulin was able to suppress damage to HBV-infected hepatocytes, suggesting an approach to treatment. This animal model is useful for virological and immunological analysis of HBV infection and to develop new therapies for severe acute hepatitis B.
Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection
Authors: Reynolds Tracy D. , Buonocore Linda , Rose Nina F. , Rose John K. , Robek Michael D.
Published: August 2015

More than 500,000 people die each year from the liver diseases that result from chronic hepatitis B virus (HBV) infection. Therapeutic vaccines, which aim to elicit an immune response capable of controlling the virus, offer a potential new treatment strategy for chronic hepatitis B. Recently, an evolved, high-titer vaccine platform consisting of Semliki Forest virus RNA replicons that express the vesicular stomatitis virus glycoprotein (VSV G) has been described. This platform generates virus-like vesicles (VLVs) that contain VSV G but no other viral structural proteins. We report here that the evolved VLV vector engineered to additionally express the HBV middle surface envelope glycoprotein (MHBs) induces functional CD8 T cell responses in mice. These responses were greater in magnitude and broader in specificity than those obtained with other immunization strategies, including recombinant protein and DNA. Additionally, a single immunization with VLV-MHBs protected mice from HBV hydrodynamic challenge, and this protection correlated with the elicitation of a CD8 T cell recall response. In contrast to MHBs, a VLV expressing HBV core protein (HBcAg) neither induced a CD8 T cell response in mice nor protected against challenge. Finally, combining DNA and VLV-MHBs immunization led to induction of HBV-specific CD8 T cell responses in a transgenic mouse model of chronic HBV infection. The ability of VLV-MHBs to induce a multispecific T cell response capable of controlling HBV replication, and to generate immune responses in a tolerogenic model of chronic infection, indicates that VLV vaccine platforms may offer a unique strategy for HBV therapeutic vaccination.

IMPORTANCEHBV infection is associated with significant morbidity and mortality. Furthermore, treatments for chronic infection are suboptimal and rarely result in complete elimination of the virus. Therapeutic vaccines represent a unique approach to HBV treatment and have the potential to induce long-term control of infection. Recently, a virus-based vector system that combines the nonstructural proteins of Semliki Forest virus with the VSV glycoprotein has been described. In this study, we used this system to construct a novel HBV vaccine and demonstrated that the vaccine is capable of inducing virus-specific immune responses in mouse models of acute and chronic HBV replication. These findings highlight the potential of this new vaccine system and support the idea that highly immunogenic vaccines, such as viral vectors, may be useful in the treatment of chronic hepatitis B.
Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations
Authors: Karakas Aram , Brumme Zabrina L. , Poon Art F. Y.
Published: August 2015

Associations between HIV-1 cytotoxic T lymphocyte (CTL) escape mutations and their restricting human leukocyte antigen (HLA) alleles imply that HIV could adapt to divergent HLA repertoires of human populations globally. Using publicly available databases, we examine the relationship between the frequencies of 19 experimentally validated CTL escape mutations in HIV-1 reverse transcriptase and their restricting HLA alleles in 59 countries. From these extensive data, we find evidence of differential HIV adaptations to human populations at only a limited number of the studied epitope sites.
Novel Bat Influenza Virus NS1 Proteins Bind Double-Stranded RNA and Antagonize Host Innate Immunity
Authors: Turkington Hannah L. , Juozapaitis Mindaugas , Kerry Philip S. , Aydillo Teresa , Ayllon Juan , García-Sastre Adolfo , Schwemmle Martin , Hale Benjamin G.
Published: August 2015

We demonstrate that novel bat HL17NL10 and HL18NL11 influenza virus NS1 proteins are effective interferon antagonists but do not block general host gene expression. Solving the RNA-binding domain structures revealed the canonical NS1 symmetrical homodimer, and RNA binding required conserved basic residues in this domain. Interferon antagonism was strictly dependent on RNA binding, and chimeric bat influenza viruses expressing NS1s defective in this activity were highly attenuated in interferon-competent cells but not in cells unable to establish antiviral immunity.
Infectious Risks of Traveling Abroad
Authors: Chen Lin H. , Blair Barbra M.
Published: August 2015

A popular leisure activity, international travel can be associated with some infections. The most common travel-related illnesses appear to be gastrointestinal, dermatologic, respiratory, and systemic febrile syndromes. The pretravel medical consultation includes immunizations, malaria chemoprophylaxis, self-treatment for traveler’s diarrhea, and advice on the prevention of a myriad of other infectious causes including dengue, chikungunya, rickettsiosis, leptospirosis, schistosomiasis, and strongyloidiasis. Travel to locations experiencing outbreaks such as Ebola virus disease, Middle East respiratory syndrome, avian influenza, and chikungunya call for specific alerts on preventive strategies. After travel, evaluation of an ill traveler must explore details of exposure, including destinations visited; activities; ingestion of contaminated food or drinks; contact with vectors, animals, fresh water, or blood and body fluids; and other potential exposures. Knowledge of the geographic distribution of infectious diseases is important in generating the differential diagnoses and testing accordingly. Empiric treatment is sometimes necessary when suspicion of a certain diagnosis is strong and confirmatory tests are delayed or lacking, particularly for infections that are rapidly progressive (for example, malaria) or for which timing of testing is prolonged (such as leptospirosis).
Chemical Biology Strategies for Biofilm Control
Authors: Yang Liang , Givskov Michael
Published: August 2015

Microbes live as densely populated multicellular surface-attached biofilm communities embedded in self-generated, extracellular polymeric substances (EPSs). EPSs serve as a scaffold for cross-linking biofilm cells and support development of biofilm architecture and functions. Biofilms can have a clear negative impact on humans, where biofilms are a common denominator in many chronic diseases in which they prime development of destructive inflammatory conditions and the failure of our immune system to efficiently cope with them. Our current assortment of antimicrobial agents cannot efficiently eradicate biofilms. For industrial applications, the removal of biofilms within production machinery in the paper and hygienic food packaging industry, cooling water circuits, and drinking water manufacturing systems can be critical for the safety and efficacy of those processes. Biofilm formation is a dynamic process that involves microbial cell migration, cell-to-cell signaling and interactions, EPS synthesis, and cell-EPS interactions. Recent progress of fundamental biofilm research has shed light on novel chemical biology strategies for biofilm control. In this article, chemical biology strategies targeting the bacterial intercellular and intracellular signaling pathways will be discussed.
Effects of Electroacupuncture at Gb Points on Markers of Osteoporosis and Bodyweight in Ovariectomised Rats
Authors: Wang Hong-Du , Chen Zhuang , Inoue Isao , Fu Shi-Jie , Shi Xiao-Lin , Tang Li , Zhang Feng-Zheng , Jiang Yang , Jiang Hua
Published: August 2015

Background

Based on a description of acupuncture to treat a bone disease resembling osteoporosis in the ancient text of Huangdi Neijing, we aimed to assess the effects of electroacupuncture (EA) at GB points in ovariectomised (OVX) rats.

Methods

40 female Wistar rats were randomly divided into four groups (n=10 each): ovariectomised model group (OVX); ovariectomised group treated with EA at GB points (OVX+GB); ovariectomised group treated with EA at non-GB points (OVX+N) in the hindlimb; and a sham surgery group (Sham). Three months after ovariectomy, rats in the OVX+GB and OVX+N groups received EA treatment for 3 months. Urine, blood and femur samples were collected from each animal for analysis.

Results

Bodyweight (BW) in the OVX+GB group decreased after EA treatment, reaching a minimum of ∼12% below the OVX and OVX+N groups at 1 month. Concentrations of urine deoxypyridinoline, a bone resorption marker, were significantly elevated in the OVX and OVX+N groups but not the OVX+GB group. Concentrations of serum bone specific alkaline phosphatase, a bone formation marker, were significantly higher in the OVX+GB group versus the Sham and OVX groups. Bone mineral density (BMD) did not differ between the OVX, OVX+GB and OVX+N groups, but was ∼10% lower than the Sham group. However, BMD/BW in the OVX+GB group was significantly higher than in the OVX and OVX+N groups and similar to the Sham group. Histological assessment of the femur showed that EA at GB points improved the bone architecture.

Conclusions

EA treatment at GB points had anti-osteoporotic effects in a rat model of osteoporosis.
Primary intraocular synovial sarcoma in the post retinal detachment operative state
Authors: Ito Junko , Suzuki Shigenobu , Yoshida Akihiko , Mori Taisuke
Published: August 2015

Synovial sarcoma generally arises in the deep soft tissue, although it has been described at virtually every anatomic site except in the eyeball. We report the case of a 48-year-old woman who had a history of retinal detachment surgery and who had undergone vitrectomy and the insertion of a solid silicon explant 24 years previously. She reported a visual field defect. Funduscopy and MRI revealed a tumour just behind the iris in the left eyeball, and enucleation was performed. Microscopic examination of the tumour revealed uniform spindle cells in a fascicular arrangement with frequent mitotic figures. Immunohistochemistry showed that the tumour was positive for TLE1 and epithelial membrane antigen and fluorescent in situ hybridisation revealed that the tumour had a rearrangement of the SYT gene. Reverse transcription (RT)-PCR confirmed the presence of a SYT-SSX2 fusion transcript. On the basis of these histomorphological and molecular features, the diagnosis of poorly differentiated synovial sarcoma was rendered.
Acute myeloid leukaemia with t(8;21)(q22;q22.3) and loss of the X chromosome
Authors: Mohamed Muhajir , Dun Karen
Published: August 2015

Cytogenetic abnormalities occur in approximately 60% of newly diagnosed patients with acute myeloid leukaemia (AML) and are useful in the risk stratification of AML. Translocation between chromosomes 8 and 21—t(8;21)—(q22;q22.3), which carries a favourable prognosis, is found in approximately 5% to 10% of all patients with AML. Additional chromosomal abnormalities have been described in patients with AML with t(8;21), which may impact on the favourable prognosis. We report a patient who had AML with t(8;21)(q22;q22.3) and loss of the X chromosome.
Acute compartment syndrome of the thigh in a rugby player
Authors: Smith Richard David James , Rust-March Holly , Kluzek Stefan
Published: August 2015

In the absence of obvious trauma, diagnosis of acute compartment syndrome (ACS) of the thigh can easily be delayed, as disproportional pain is not always present. We present a case of ACS of the anterior right thigh compartment in a healthy, semiprofessional rugby player with normal coagulation, who sustained a seemingly innocuous blow during a rugby match. Following early surgical fasciotomy, he returned to his preinjury playing standards within 12 months. Our literature review suggests that high muscle mass, young, athletic males participating in a contact sport are mostly at risk of developing ACS of the thigh.
Hibernoma larynx with large multinodular goitre: unusual airway challenge
Authors: Iftikhar Haissan , Siddiqui Moghira Iqbaluddin
Published: August 2015

A 56-year-old man presented with a 6-month history of progressively increasing neck swelling, dysphagia and hoarseness of voice. CT scan revealed multi-nodular goitre and also showed a lesion in the supraglottis. It also showed another lesion in the supraglottis. Fine-needle aspiration cytology of thyroid revealed follicular cells. Routine flexible laryngoscopy was performed to evaluate vocal cord function; however, we found a smooth well-defined lesion just above the glottis, obstructing the direct view of the vocal cords, and an endangered airway. A provisional diagnosis of a laryngeal cyst was made. With all necessary precautions intubation was performed with a bougie and a reinforced endotracheal tube was inserted. Total thyroidectomy was performed first. With direct suspension laryngoscopy an attempt was made to deliver the laryngeal lesion, however, the lesion could not be removed. A suprahyoid lateral pharyngotomy was performed to deliver the lesion. Histopathology of the lesion revealed hibernoma.
Injury data of major international field hockey tournaments
Authors: Theilen Till-Martin , Mueller-Eising Wiebke , Wefers Bettink Peter , Rolle Udo
Published: August 2015

Background

Detailed injury data are not available for international tournaments in field hockey. We investigated the epidemiology of field hockey injuries during major International Hockey Federation (Fédération Internationale de Hockey, FIH) tournaments in 2013.

Materials and methods

FIH injury reports were used for data collection. All major FIH tournaments for women (n=5) and men (n=11) in 2013 were included. The main focus of this study was to assess the pattern, time, site on the pitch, body site and mechanism of each of the injuries. We calculated the average number of injuries per match and the number of injuries per 1000 player match hours.

Results

The average number of injuries was 0.7 (95% CI 0.5 to 1.0) per match in women's tournaments and 1.2 (95% CI 0.8 to 1.7) per match in men's tournaments. The number of injuries per 1000 player match hours ranged from 23.4 to 44.2 (average 29.1; 95% CI 18.6 to 39.7) in women and 20.8 to 90.9 (average 48.3; 95% CI 30.9 to 65.8) in men. Most injuries occurred in the circle (n=25, 50%, in women, n=95, 51%, in men). The rate of injuries increased after the first quarter. Injuries to the head and face (n=20, 40%) were most common in women. The head/face (n=51, 27%) and the thigh/knee (n=52, 28%) were equally affected in men. The ball caused the most injuries, followed by the stick, collisions and tripping/falling. There were no deaths or injuries that required hospital treatment in the entire cohort.

Field hockey has a low incidence of acute injuries during competition.