bluuebunny/crossref_metadata_2025 huggingface dataset:
Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement
Authors: Horneff Gerd , Fitter Sigrid , Foeldvari Ivan , Minden Kirsten , Kuemmerle-Deschner Jasmin , Tzaribacev Nicolay , Thon Angelika , Borte Michael , Ganser Gerd , Trauzeddel Rolf , Huppertz Hans-Iko
Published: October 2012

Introduction

While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS).

Methods

A total of 32 patients aged 12 to 17 years with severe, active and refractory JoAS were enrolled in a multicenter, randomized, double-blind, placebo-controlled parallel study of 12 weeks, followed by open-label adalimumab until week 24 for all patients. ASAS40 was used as the primary, and ASAS20, PedACR and single items were used as the secondary outcome measures for the intention to treat population.

Results

A total of 17 patients were randomized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo. Two patients (one of each group) discontinued prematurely due to insufficient efficacy and were labeled as non-responders. In the double-blind part, more patients on adalimumab achieved an ASAS40 at week 4 (41%), week 8 (53%) and week 12 (53%) than on placebo (20%, 33%, 33%), while differences at week 8 only reached borderline significance (P = 0.05). Also, at 4, 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group (53%/53%/29%; 59%/76%/41%; 53%/65%/53%) compared to placebo (27%/27%/7%; 27%/33%/13%; 33%/40%/27%). In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24. At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65% (P <0.001), the back pain score decreased by 50% (P <0.005), the Bath AS Functional Index (BASFI) score decreased by 47% (P <0.02), while the Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) score improved by 65% (P <0.005). ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity, parents' global assessment of subject's overall well-being, active joint count (all P <0.05) and erythrocyte sedimentation rate (ESR) (P <0.01).

During the 12-week controlled phase, 29 AEs occurred in 10 patients on placebo compared to 27 AEs in 11 patients on adalimumab. Injection site reactions were the most common adverse events. There were 17 various infections occurring in the double-blind phase, 8 on placebo, 9 on adalimumab and a further 19 in the open label period.

Conclusions

Adalimumab was well tolerated and highly effective in a double-blind randomized trial in patients with JoAS. Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment.

Trial registration

EudraCT 2007-003358-27.
Sp1 and Sp3 Transcription Factors Mediate Leptin-Induced Collagen α1(I) Gene Expression in Primary Culture of Male Rat Hepatic Stellate Cells
Authors: García-Ruiz Inmaculada , Gómez-Izquierdo Erica , Díaz-Sanjuán Teresa , Grau Montserrat , Solís-Muñoz Pablo , Muñoz-Yagüe Teresa , Solís-Herruzo José A.
Published: October 2012

Mechanisms by which leptin stimulates collagen α1(I) [Col1a(I)] gene expression are unclear. The purposes of this study were to identify the trans-acting factors and cis-acting elements in Col1a(I) promoter involved in this effect as well as the pathways that are implicated. In primary cultures of rat hepatic stellate cells (HSCs), we measured the effects of leptin on Col1a(I) gene and protein expression and on the binding of nuclear proteins to the Col1a(I) promoter. We found that leptin increased Col1a(I) gene and protein expression in activated HSCs. Transient transfections showed that leptin exerted its effects through elements located between −220 and −112 bp of the Col1a(I) promoter. Gel retardation assays demonstrated that leptin induced the binding of transcription factors specific protein (Sp)-1 and Sp3 to two elements located between −161 and −110 bp of the Col1a(I) promoter. Leptin-induced Sp1/Sp3 phosphorylation, but this effect was suppressed by inhibiting or silencing Janus kinase-2, phosphatidylinositol-3-kinase, nonphagocytic adenine dinucleotide phosphate (NADPH) oxidase, or ERK1/2, by the use of antioxidants or catalase, or by preventing protein-aldehyde adduct formation. Leptin provoked oxidative stress, aldehyde-protein adduct formation, and increased gene expression of some components of the NADPH oxidase complex. In conclusion, in HSCs, leptin up-regulates Col1a(I) gene expression after activating NADPH oxidase, inducing oxidative stress, aldehyde-protein adduct formation, and ERK1/2 phosphorylation, which in turn activates Sp1/Sp3 and provokes the binding of these two factors to regulatory elements located between −161 and −110 bp of the Col1a(I) promoter. These findings may contribute to a better understanding of mechanisms involved in the leptin-induced liver fibrosis.
Body dynamics and hydrodynamics of swimming fish larvae: a computational study
Authors: Li Gen , Müller Ulrike K. , van Leeuwen Johan L. , Liu Hao
Published: October 2012

To understand the mechanics of fish swimming, we need to know the forces exerted by the fluid and how these forces affect the motion of the fish. To this end, we developed a 3-D computational approach that integrates hydrodynamics and body dynamics. This study quantifies the flow around a swimming zebrafish (Danio rerio) larva. We used morphological and kinematics data from actual fish larvae aged 3 and 5 days post fertilization as input for a computational model that predicted free-swimming dynamics from prescribed changes in body shape. We simulated cyclic swimming and a spontaneous C-start. A rigorous comparison with 2-D particle image velocimetry and kinematics data revealed that the computational model accurately predicted the motion of the fish's centre of mass as well as the spatial and temporal characteristics of the flow. The distribution of pressure and shear forces along the body showed that thrust is mainly produced in the posterior half of the body. We also explored the effect of the body wave amplitude on swimming performance by considering wave amplitudes that were up to 40% larger or smaller than the experimentally observed value. Increasing the body wave amplitude increased forward swimming speed from 7 to 21 body lengths per second, which is consistent with experimental observations. The model also predicted a non-linear increase in propulsive efficiency from 0.22 to 0.32 while the required mechanical power quadrupled. The efficiency increase was only minor for wave amplitudes above the experimental reference value, whereas the cost of transport rose significantly.
Performance and scaling of a novel locomotor structure: adhesive capacity of climbing gobiid fishes
Authors: Maie Takashi , Schoenfuss Heiko L. , Blob Richard W.
Published: October 2012

Many species of gobiid fishes adhere to surfaces using a sucker formed from fusion of the pelvic fins. Juveniles of many amphidromous species use this pelvic sucker to scale waterfalls during migrations to upstream habitats after an oceanic larval phase. However, adults may still use suckers to re-scale waterfalls if displaced. If attachment force is proportional to sucker area and if growth of the sucker is isometric, then increases in the forces that climbing fish must resist might outpace adhesive capacity, causing climbing performance to decline through ontogeny. To test for such trends, we measured pressure differentials and adhesive suction forces generated by the pelvic sucker across wide size ranges in six goby species, including climbing and non-climbing taxa. Suction was achieved via two distinct growth strategies: (1) small suckers with isometric (or negatively allometric) scaling among climbing gobies and (2) large suckers with positively allometric growth in non-climbing gobies. Species using the first strategy show a high baseline of adhesive capacity that may aid climbing performance throughout ontogeny, with pressure differentials and suction forces much greater than expected if adhesion were a passive function of sucker area. In contrast, large suckers possessed by non-climbing species may help compensate for reduced pressure differentials, thereby producing suction sufficient to support body weight. Climbing Sicyopterus species also use oral suckers during climbing waterfalls, and these exhibited scaling patterns similar to those for pelvic suckers. However, oral suction force was considerably lower than that for pelvic suckers, reducing the ability for these fish to attach to substrates by the oral sucker alone.
Honeybees consolidate navigation memory during sleep
Authors: Beyaert Lisa , Greggers Uwe , Menzel Randolf
Published: October 2012

Sleep is known to support memory consolidation in animals, including humans. Here we ask whether consolidation of novel navigation memory in honeybees depends on sleep. Foragers were exposed to a forced navigation task in which they learned to home more efficiently from an unexpected release site by acquiring navigational memory during the successful homing flight. This task was quantified using harmonic radar tracking and applied to bees that were equipped with a radio frequency identification device (RFID). The RFID was used to record their outbound and inbound flights and continuously monitor their behavior inside the colony, including their rest during the day and sleep at night. Bees marked with the RFID behaved normally inside and outside the hive. Bees slept longer during the night following forced navigation tasks, but foraging flights of different lengths did not lead to different rest times during the day or total sleep time during the night. Sleep deprivation before the forced navigation task did not alter learning and memory acquired during the task. However, sleep deprivation during the night after forced navigation learning reduced the probability of returning successfully to the hive from the same release site. It is concluded that consolidation of novel navigation memory is facilitated by night sleep in bees.
Diagnosis of acetabular labral tears: Comparison of three-dimensional intermediate-weighted fast spin-echo MR arthrography with two-dimensional MR arthrography at 3.0 T
Authors: Park So Young , Park Ji Seon , Jin Wook , Rhyu Kee Hyung , Ryu Kyung Nam
Published: October 2012

Background

Magnetic resonance (MR) arthrography is the ideal imaging modality for the acetabular labrum. Three-dimensional (3D) fast spin-echo (FSE) sequences have similar diagnostic performance as two-dimensional (2D) conventional MR imaging for ligaments, menisci, or bone marrow edema in the knee.

Purpose

To compare the diagnostic accuracy and inter-observer reliability of 3D intermediate-weighted FSE sequence and 2D FSE sequences for the diagnosis of acetabular labral tears.

Material and Methods

Institutional review board approval was obtained and informed consent was waived for 45 patients (47 hips) who underwent 3D and 2D MR arthrography and subsequent arthroscopic surgery. The 3D sequences were performed using volumetric intermediate-weighted fast spin-echo imaging with fat suppression (voxel size, 0.6 × 0.6 × 1.2 mm; imaging time, 6 min 38 s). Labral tear was retrospectively and independently evaluated by two radiologists in four areas of the labrum (anterosuperior, posterosuperior, anteroinferior, and posteroinferior) on 3D and 2D FSE sequences. Statistical differences between the sensitivity and specificity of the methods were analyzed with the McNemar test, using arthroscopic findings as the reference standard. Inter-observer agreement was calculated using kappa statistics.

Results

Arthroscopic findings confirmed labral tears at 40 anterosuperior, 23 posterosuperior, 0 anteroinferior, and 2 posteroinferior quadrants. Sensitivity and specificity were 74% and 89% for 2D FSE sequences, and 78% and 92% for 3D FSE sequences, respectively. Sensitivities and specificities for the methods were not different statistically (P > 0.05). Inter-observer agreement for labral tear was substantial for 2D FSE sequences (k = 0.774) and almost perfect for 3D FSE sequences (k = 0.842).

Conclusion

3D intermediate-weighted FSE MR arthrography is excellent for diagnosing acetabular labral tears. Sensitivity, specificity, and inter-observer reliability were similar to conventional 2D MR arthrography. For evaluation of the labrum, 3D FSE MR arthrography is more time-efficient than 2D FSE MR arthrography.
Estimation of glomerular filtration rate in rabbits by a single-sample method using iodixanol
Authors: Michigoshi Y , Katayama R , Yamagishi N , Kato M , Saito J , Satoh H , Furuhama K
Published: October 2012

To estimate the glomerular filtration rate (GFR) in conscious rabbits, a single-sample method using the non-ionic contrast medium iodixanol was compared with a three-sample method using the standard agent inulin. Iodixanol and inulin were co-administered intravenously to male New Zealand White rabbits at 60 mg I/kg and 40 mg/kg, respectively, and blood was collected 30, 60, 90 and 120 min later. Serum iodixanol and inulin concentrations were separately determined by high performance liquid chromatography and colorimetry, respectively. Serum urea nitrogen (UN) and creatinine concentrations were also determined. Based on the data from healthy and cisplatin-treated rabbits, the GFR estimated by iodixanol was well consistent with that by inulin. Further, when the GFR decreased to more than 60% of the reference value, serum creatinine concentrations became elevated. However, serum UN concentrations exhibited wide fluctuations, presumably due to a difference in renal handlings. The single-sample method using iodixanol was considered to be an expedient tool in both clinical and research settings, because the stress due to a multi-sample method was reduced.
Individual housing of female mice: influence on postsurgical behaviour and recovery
Authors: Jirkof Paulin , Cesarovic Nikola , Rettich Andreas , Fleischmann Thea , Arras Margarete
Published: October 2012

Individual housing of laboratory mice may increase vulnerability to surgical stress, and interfere with postsurgical recovery. To analyse the effect of housing conditions on recovery, pair- and single-housed female C57BL/6J mice underwent a minor laparotomy +/− analgesia, anaesthesia only or no treatment. Animals were monitored using non-invasive methods during the immediate postsurgical period to assess pain and general impairment. While no appearance or posture abnormalities were observed postexperiment, home cage behaviours were affected distinctly. Discriminant analysis identified self-grooming, locomotion, climbing and resting as mainly responsible for experimental group separation. Behavioural rhythmicity was disrupted, and behaviours related to wellbeing, such as nest building, climbing and burrowing, decreased. Behavioural pain signs (e.g. press) increased. Most behavioural alterations showed a gradation between treatments, e.g. burrowing latency ranged from an intermediate level following anaesthesia only and surgery with analgesia, to pronounced prolongation after surgery without analgesia. Significantly lower burrowing performance after surgery without analgesia in individually-housed animals indicates better recovery in pairs. Social interaction in pairs – an important component of normal behaviour (64%) and a potential indicator for direct social support – was nearly absent (0.3–0.5%). While anaesthesia and surgery resulted in clear changes in behaviour, differences between housing conditions were minor. Hence, despite a tendency towards better recovery in pairs, we found no distinct negative effect of individual housing. In conclusion, both housing conditions are acceptable during the period immediately following minor surgery, though social housing is always preferable in female mice.
Selective inbreeding does not increase gut microbiota similarity in BALB/c mice
Authors: Pang Wanyong , Stradiotto Damiano , Krych Lukasz , Karlskov-Mortensen Peter , Vogensen Finn Kvist , Nielsen Dennis Sandris , Fredholm Merete , Hansen Axel Kornerup
Published: October 2012

Inflammatory diseases in mouse models are under strong impact from the gut microbiota. Therefore increased interindividual gut microbiota similarity may be seen as a way to reduce group sizes in mouse experiments. The composition of the gut microbiota is to a high extent defined by genetics, and it is known that selecting siblings as mothers even in inbred colonies may increase the gut microbiota similarity among the mice with 3–4%. We therefore hypothesized that selective breeding of mice aiming at a high similarity in the gut microbiota would increase the interindividual similarity of the gut microbiota. BALB/cCrl mice were, however, found to have a mean heterozygosity of only 0.8% in their genome, and selection of breeders with a high similarity in the gut microbiota for three generations did not change the overall gut microbiota similarity, which was 66% in the P generation and 66%, 64% and 63% in the F1, F2 and F3 generations, respectively. Increased gut microbiota similarity in closely related mice in inbred mouse colonies is, therefore, more likely to be caused by other factors, such as imprinting or different intrauterine conditions, rather than by residual heterozygosity.
Optimizing the dosing interval of buprenorphine in a multimodal postoperative analgesic strategy in the rat: minimizing side-effects without affecting weight gain and food intake
Authors: Schaap Manon W H , Uilenreef Joost J , Mitsogiannis Manuela D , van 't Klooster José G , Arndt Saskia S , Hellebrekers Ludo J
Published: October 2012

Buprenorphine is commonly used as (part of) postoperative analgesic treatment with dosage dependent side-effects such as pica behaviour. No strict consensus exists about the optimal dosing interval of buprenorphine, as its duration of action has been described as being in the range of 6–12 h. In this study, dosing intervals of 8 h (thrice-a-day) and 12 h (twice-a-day) for buprenorphine in a multimodal analgesic strategy (concurrent administration of a non-steroidal anti-inflammatory drug) were compared on food intake, weight and side-effects (gnawing on plastic Petri dishes and growth rate, indicative of pica behaviour) in rats. The food intake and weight of both intervals were comparable, as the animals from the twice-a-day group did not lose more weight or consumed less food during the analgesic period. The rats from the thrice-a-day group suffered from more side-effects, as the growth rate was decreased and more plastic was gnawed on. It is recommended to carefully evaluate analgesic and side-effects when using buprenorphine. When side-effects are observed, the possibility of increasing the dosing interval of buprenorphine should be explored. In this study, increasing the dosing interval of buprenorphine in a multimodal analgesic regimen resulted in reduced unwanted side-effects, without increasing weight loss or decreasing food intake. Although this is suggestive of provision of comparable analgesia, future studies including more pain-related readout parameters to assess the effect of the dosing interval on analgesic efficacy are recommended.
Development of a rat respiratory mask and its application in experimental chronic myocardial ischaemia
Authors: Wang Yue-Min , Fan Rong , Li Juan , Zhang Li-Jun , Shi Quan-Xing , Xu Xu-Zeng , Yu Shi-Qiang , Yi Ding-Hua , Kaye Aaron Joshua , Bueno Franklin Rivera , Kaye Alan David , Pei Jian-Ming
Published: October 2012

In addressing the challenge of the low survival rates of rats with myocardial ischaemia, we developed a novel respiratory mask. We tested this mask on the rat model. We gave attention to several features of the mask: (1) shape, (2) size, (3) inlet, (4) outlet, (5) compatibility between rat head and the mask, (6) connection between mask and ventilator. We found certain features, especially to influence mask efficacy. These features include: mask shape, mask inlet and outlet, mask connection to the respiratory machine, mask mount on the rat head. We examined the rat mask in a model of chronic myocardial ischaemia; our model was the ligation of the coronary artery. The rats with the masks experienced an increase in survival by a factor of 50–90% compared with rats deprived of the masks. Towards the examination of myocardial ischaemia, our new mask may offer a platform replete with both efficiency and stability.
Type 2 diabetes care for patients in a tertiary care setting in UAE: a retrospective cohort study
Authors: Alhyas Layla , Cai Yutong , Majeed Azeem
Published: October 2012

Objective

We aimed to examine the quality of type 2 diabetes mellitus (T2DM) care in Al-Ain, in the United Arab Emirates (UAE).

Design

A retrospective cohort study from 2008 to 2010.

Setting

A diabetes centre located in a tertiary care hospital in Al-Ain, UAE.

Participants

People with T2DM receiving care from the diabetes centre.

Results

382 Emirates patients with T2DM were included in the analysis. Overall in 2010, proportions of people with T2DM reaching the following targets were: glycated haemoglobin (HbA1c) 41%, low-density lipoprotein (LDL) 72%, systolic and diastolic blood pressure (SBP/DBP) 47% and 73%, respectively. There was a significant improvement from 2008 to 2010, respectively, in the mean for the following: (1) HbA1c (8.5% [95% confidence interval, CI: 8.33–8.67] versus 7.5% [95% CI: 7.36–7.63]); (2) LDL (2.60 mmol/L [95% CI: 2.51–2.70] versus 2.27 mmol/L [95% CI: 2.21–2.33]); and (3) SBP (133.1 mmHg [95% CI: 131.7–134.4] versus 131.0 [95% CI: 130.1–131.9]). Glycaemic and lipid control were similar in men and women; however, HbA1c levels in men and women aged 60+ years were significantly lower by (0.7% [ P = 0.01] versus 0.8% [ P < 0.001], respectively) than for those aged between 18 and 39 years.

Conclusion

This study demonstrates that there is encouraging progress in diabetes care in Al-Ain, UAE as reflected by the overall improvement in the mean of HbA1c, LDL and SBP, and the increase in the number of people reaching the target for the same indicators from 2008 to 2010. The results however show that there is scope for additional enhancement of care, especially for better glycaemic control among young patients and better SBP control among men.
Reservoir Characteristics and its Main Controlling Factors of the Siegenian Formation of Devonian in X Block, Algeria
Authors: Zhang Chunming , Jiang Zaixing , Zhang Yuanfu , Chen Qi , Zhao Wei , Xu Jie
Published: October 2012

The Siegenian Formation reservoir is a tight sandstone reservoir with relatively poor porosity and low permeability. In this paper, the reservoir characteristics and its main controlling factors of the Siegenian Formation in X block have been studied based on cores, well-logs, and formation test data including the thin sections and cast thin sections, observation of scanning electron microscope, pressured-mercury testing and X-ray diffraction analysis of clay minerals. During deposition of the Siegenian Formation, the depositional environment was predominated by lower shoreface, middle shoreface and offshore. The fine sandstone and siltstone formed in the middle shoreface environment is the main reservoir of the Siegenian Formation in X block. Six pore types including primary intergranular pores, intragranular dissolved pores, intergranular dissolved pores, moldic pores, cement dissolved pores and microfractures are identified in the Siegenian Formation reservoir. The quartz intergranular dissolved pores and the quartz overgrowth cement dissolved pores are found for the first time in this area. The secondary dissolution pore is the main pore type in X block. The pore throat has a small radius, poor connectivity and the pore structure parameters are poor. Combined with the petrophysical property and capillary pressure curves, the reservoir of the research area is divided into three types: mesopore-ultra low permeability reservoir (type I), low-middle porosityultra low permeability reservoir (type II) and low porosity-ultra low permeability reservoir (type III). Type II is the main reservoir in this area. The sedimentary environment, tectonism and diagenesis are the main controlling factors. Diagenesis is the most important controlling factor in this area. Diagenesis may play a catalytic role or may play a negative role on damage in the reservoir pore evolution. The compaction, pressure solution, cementation, replacement and cementation are the main diagenesis types which reduce the pore volume during the reservoir pore evolution. The dissolution including acidic dissolution and alkaline dissolution are the main diagenesis types which produce extra pore volume during the reservoir pore evolution. This study of the reservoir will guide the future exploration of this area.
Transesterification of Jatropha Curcas Oil to Biodiesel by Using Short Necked Clam (Orbicularia Orbiculata) Shell Derived Catalyst
Authors: Taufiq-Yap Y.H. , Lee H.V. , Lau P.L.
Published: October 2012

Investigation has been conducted to develop an environmental friendly and economically feasible process for biodiesel production. Natural short necked clam shell was utilized as calcium oxide (CaO) source for transesterification of non-edible Jatropha curcas oil to biodiesel. The powdered clam shell was calcined at 900°C for 3 h to transform calcium carbonate (CaCO3) in shell to active CaO catalyst. The effect of catalyst loading, methanol to oil molar ratio and reaction time on fatty acid methyl ester (FAME) yield was investigated. Under optimal condition, biodiesel yield achieved 93% within 6 h at 65°C. As a result, the catalytic activity of waste clam shell-derived catalyst is comparable to commercial CaO catalyzed reaction. Hence, it can be used as another renewable yet cost-effective catalyst source for biodiesel production.
Noise Radiation from a Continuous Mold-Line Link Flap Configuration
Authors: Hutcheson Florence V. , Brooks Thomas F. , Humphreys William M.
Published: October 2012

The results of an experimental study of the noise from a Continuous Mold-Line Link (CML) flap are presented. Acoustic and unsteady surface pressure measurements were performed on a main element wing section with a half-span CML flap in NASA Langley's Quiet Flow Facility. The acoustic data were acquired with a medium aperture directional array (MADA) of microphones. The Deconvolution Approach for the Mapping of Acoustic Sources (DAMAS) method is applied to determine the spatial distribution and strength of the noise sources over the surface of the test model. A Coherent Output Power (COP) method which relates the output from unsteady surface pressure sensors to the output of the MADA is also used to obtain more detailed characteristics of the noise source distribution in the trailing edge region of the CML. These results are compared to those obtained for a blunt flap to quantify the level of noise benefit that is achieved with the CML flap. The results indicate that the noise from the CML region of the flap is 5 to 17 dB lower (depending on flap deflection and Mach number) than the noise from the side edge region of the blunt flap. Lower noise levels are obtained for all frequencies. Spectral analysis of the noise from the cove region of the CML and blunt flap models also reveal a spectral peak in the high frequency range that is related to noise scattering at the trailing edge of the main element. The peaks in the CML and blunt flap cove noise spectra are close in level and often exceed blunt side edge noise. Applying a strip of serrated tape to the trailing edge of the CML flap model main airfoil reduced the peak but increased other noise somewhat. Directivity measurements show that the CML flap can be more directional than the blunt flap.
Properties of the Far-Field Pressure Signatures of Individual Jet Noise Sources
Authors: Lewalle Jacques , Low Kerwin R. , Glauser Mark N.
Published: October 2012

The detection of intermittent near-field noise sources is achieved by continuous wavelet transform of far-field acoustic data. The similarities between signals from three far-field microphones in the annular cone of acoustic radiation from coherent sources in a Ma = 0.6 cold jet are used to identify some of the loudest events. Cross-correlation of relevant band-passed excerpts identifies the most reliable matches, which occur at the rate of one every 20 dimensionless time units on average, and are intermittent in both time and frequency with no obvious pattern. Processing our database produced a catalog of over 9500 individual events with quantitative properties including the magnitude, frequency and time of detection at each microphone. The differences in detection times (lags) are distributed smoothly around the peak of cross-correlations for the raw data. We show how source magnitude and frequency depends on lags, and relate the lags to their relative source location.
Measurement of the Noise Resulting from the Interaction of Turbulence with a Lifting Surface
Authors: Hutcheson Florence V. , Brooks Thomas F. , Stead Daniel J.
Published: October 2012

An experimental study of the noise resulting from the interaction of an airfoil with incident turbulence is presented. The test models include NACA0015 airfoils of different chord lengths, a flat plate with a sharp leading edge, and an airfoil of same section as a reference Fowler flap. The airfoils are immersed in nearly isotropic turbulence. Two approaches for performing the noise measurements are used and compared. The effects that turbulence intensity and integral length scales, airfoil geometry, velocity and angle of attack have on the incident turbulence interaction noise are examined. Detailed directivity measurements are presented. It is found that noise spectral levels beyond the peak frequency decrease at a slower rate for the sharper airfoil leading edges, and that spectral peak level (at 0° angle of attack) appears to be mostly controlled by the airfoil's thickness and chord. Increase in turbulence integral scale and intensity are observed to lead to a uniform increase of the noise spectral levels with an LI2 dependence (where L is the turbulence longitudinal integral scale and I is the turbulence intensity). Noise levels are found to scale with the 6th power of velocity and the 2nd power of the airfoil chord. Sensitivity to changes in angle of attack appears to have a turbulence longitudinal integral scale to chord (C) ratio dependence, with large effects on noise for L/C ≥ 1 and decreased effects as L/C becomes smaller than 1. For all L/C values, the directivity pattern of the noise resulting from the incident turbulence is seen to remain symmetric with respect to the direction of the mean flow until stall, at which point, the directivity becomes symmetric with respect to the airfoil chord. It is also observed that sensitivity to angle of attack changes is more pronounced on the model suction side than on the model pressure side, and in the higher frequency range of the spectra for the largest airfoils tested (L/C < 0.24).
Kinetic analysis of pre-ribosome structure in vivo
Authors: Swiatkowska Agata , Wlotzka Wiebke , Tuck Alex , Barrass J. David , Beggs Jean D. , Tollervey David
Published: October 2012

Pre-ribosomal particles undergo numerous structural changes during maturation, but their high complexity and short lifetimes make these changes very difficult to follow in vivo. In consequence, pre-ribosome structure and composition have largely been inferred from purified particles and analyzed in vitro. Here we describe techniques for kinetic analyses of the changes in pre-ribosome structure in living cells of Saccharomyces cerevisiae. To allow this, in vivo structure probing by DMS modification was combined with affinity purification of newly synthesized 20S pre-rRNA over a time course of metabolic labeling with 4-thiouracil. To demonstrate that this approach is generally applicable, we initially analyzed the accessibility of the region surrounding cleavage site D site at the 3′ end of the mature 18S rRNA region of the pre-rRNA. This revealed a remarkably flexible structure throughout 40S subunit biogenesis, with little stable RNA–protein interaction apparent. Analysis of folding in the region of the 18S central pseudoknot was consistent with previous data showing U3 snoRNA–18S rRNA interactions. Dynamic changes in the structure of the hinge between helix 28 (H28) and H44 of pre-18S rRNA were consistent with recently reported interactions with the 3′ guide region of U3 snoRNA. Finally, analysis of the H18 region indicates that the RNA structure matures early, but additional protection appears subsequently, presumably reflecting protein binding. The structural analyses described here were performed on total, affinity-purified, newly synthesized RNA, so many classes of RNA and RNA–protein complex are potentially amenable to this approach.
Uncommon Dantzig-Wolfe Reformulation for the Temporal Knapsack Problem
Authors: Caprara Alberto , Furini Fabio , Malaguti Enrico
Published: October 2012

We study a natural generalization of the knapsack problem, in which each item exists only for a given time interval. One has to select a subset of the items (as in the classical case), guaranteeing that for each time instant, the set of existing selected items has total weight no larger than the knapsack capacity. We focus on the exact solution of the problem, noting that prior to our work, the best method was the straightforward application of a general-purpose solver to the natural integer linear programming formulation. Our results indicate that much better results can be obtained by using the same general-purpose solver to tackle a nonstandard Dantzig-Wolfe reformulation in which subproblems are associated with groups of constraints. This is also interesting because the more natural Dantzig-Wolfe reformulation of single constraints performs extremely poorly in practice.
Combination Therapy for the Treatment and Prevention of Hepatic Encephalopathy
Authors: Mohammad Rima A , Regal Randolph E , Alaniz Cesar
Published: October 2012

OBJECTIVE:

To evaluate the efficacy and safety of combination therapy for the treatment and prevention of hepatic encephalopathy (HE).

DATA SOURCES:

A PubMed MEDLINE search was conducted (1947-June 2012) using the key terms lactulose, lactitol, nonabsorbable disaccharide, metronidazole, rifaximin, neomycin, probiotics, and hepatic encephalopathy. Searches were limited to include articles published in English.

STUDY SELECTION AND DATA EXTRACTION:

Study selection included published trials, case reports, and case series of humans with HE who were treated with combination therapy of rifaximin, lactulose, lactitol, metronidazole, neomycin, and/or probiotics.

DATA SYNTHESIS:

Only 6 studies that evaluated the benefits of combination drug therapy in the treatment or prevention of HE were available for review. Four studies addressed the treatment of HE, 2 found no significant difference between lactulose/neomycin versus placebo or rifaximin/lactulose, 1 assessed the use of rifaximin/lactulose without a control group, and the fourth found no significant difference between lactulose/probiotics versus either drug alone, although each group showed improvement from baseline. In the 2 prevention trials, both of which stemmed from the same data, the combination of rifaximin/lactulose was superior to lactulose alone, showing significant improvement in mental status, blood ammonia levels, and health-related quality of life and reductions in HE recurrence and hospitalization. Currently, there are no available clinical studies evaluating dual antibiotic therapy, metronidazole with nonabsorbable disaccharides, or antibiotics with probiotics.

CONCLUSIONS:

The evidence evaluating the use of combination therapy for the treatment of HE does not support its widespread use. The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy. The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence.
Mixed Treatment Comparison of the Treatment Discontinuations of Biologic Disease-Modifying Antirheumatic Drugs in Adults with Rheumatoid Arthritis
Authors: Desai Rishi J , Hansen Richard A , Rao Jaya K , Wilkins Tania M , Harden Elizabeth A , Yuen Andrea , Jonas Daniel E , Roubey Robert , Jonas Beth , Gartlehner Gerald , Lux Linda , Donahue Katrina E
Published: October 2012

BACKGROUND:

Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has considerably changed treatment options for rheumatoid arthritis (RA) over the past decade. Very little information is available on comparative discontinuation rates of the biologics.

OBJECTIVE:

To compare treatment discontinuations for 9 biologic DMARDs in adults with RA.

METHODS:

We searched electronic databases through May 2012 to retrieve randomized controlled trials (RCTs) of patients with RA that compared biologic DMARDs with placebo or another biologic DMARD. The primary outcome was treatment discontinuation during the blinded phase of the trials, measured as overall withdrawals, withdrawals resulting from lack of efficacy, and withdrawals resulting from adverse events. Random-effects meta-analysis estimated the effect size for individual agents, and adjusted indirect comparisons were made between biologics using mixed treatment comparisons (MTC) meta-analysis.

RESULTS:

Forty-four trials were included in the analysis. In comparison with placebo, biologics were less likely to be withdrawn because of lack of efficacy (OR 0.22, 95% CI 0.17 to 0.27) and more likely to be withdrawn because of an adverse event (OR 1.41, 95% CI 1.16 to 1.70). Based on the MTC, certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates resulting from lack of efficacy than adalimumab, anakinra, and infliximab. Anakinra had higher relative withdrawal rates resulting from lack of efficacy than most other biologics. Certolizumab and infliximab had more, while etanercept had fewer, withdrawals because of adverse events than most other drugs.

CONCLUSIONS:

Based on MTC using data from RCTs, differences in discontinuation rates were observed, generally favoring certolizumab, etanercept, and rituximab over other biologic DMARDs. These potential differences need to be further explored in head-to-head trials or well-conducted observational studies.
Synthesis and electrochemical properties of ferrocene dimers and trimers bridged by an oligothiophene spacer
Authors: Muraoka Hiroki , Ogawa Satoshi
Published: October 2012

We describe the design and synthesis of ferrocene dimers and trimers bridged by an oligothiophene spacer as both cathodic and anodic multiple redox-active organic–organometallic hybrid molecules. The electrochemical properties of all compounds were examined by cyclic voltammetry (CV). The voltammograms showed different multi-step, multi-electron redox reactions derived from multi-ferrocene fragments and the organic spacer. The results indicate that a number of thiophene rings in the spacer can be attuned to the redox potentials and the electron-transfer processes.
Endothelial Tip Cells in Ocular Angiogenesis
Authors: Siemerink Martin J. , Klaassen Ingeborg , Van Noorden Cornelis J.F. , Schlingemann Reinier O.
Published: October 2012

Endothelial tip cells are leading cells at the tips of vascular sprouts coordinating multiple processes during angiogenesis. In the developing retina, tip cells play a tightly controlled, timely role in angiogenesis. In contrast, excessive numbers of tip cells are a characteristic of the chaotic pathological blood vessels in proliferative retinopathies. Tip cells control adjacent endothelial cells in a hierarchical manner to form the stalk of the sprouting vessel, using, among others, the VEGF-DLL-Notch signaling pathway, and recruit pericytes. Tip cells are guided toward avascular areas by signals from the local extracellular matrix that are released by cells from the neuroretina such as astrocytes. Recently, tip cells were identified in endothelial cell cultures, enabling identification of novel molecular markers and mechanisms involved in tip cell biology. These mechanisms are relevant for understanding proliferative retinopathies. Agents that primarily target tip cells can block pathological angiogenesis in the retina efficiently and safely without adverse effects. A striking example is platelet-derived growth factor, which was recently shown to be an efficacious additional target in the treatment of retinal neovascularization. Here we discuss these and other tip cell-based strategies with respect to their potential to treat patients with ocular diseases dominated by neovascularization.
Mapping a Complete Neural Population in the Retina
Authors: Marre Olivier , Amodei Dario , Deshmukh Nikhil , Sadeghi Kolia , Soo Frederick , Holy Timothy E. , Berry Michael J.
Published: October 2012

Recording simultaneously from essentially all of the relevant neurons in a local circuit is crucial to understand how they collectively represent information. Here we show that the combination of a large, dense multielectrode array and a novel, mostly automated spike-sorting algorithm allowed us to record simultaneously from a highly overlapping population of >200 ganglion cells in the salamander retina. By combining these methods with labeling and imaging, we showed that up to 95% of the ganglion cells over the area of the array were recorded. By measuring the coverage of visual space by the receptive fields of the recorded cells, we concluded that our technique captured a neural population that forms an essentially complete representation of a region of visual space. This completeness allowed us to determine the spatial layout of different cell types as well as identify a novel group of ganglion cells that responded reliably to a set of naturalistic and artificial stimuli but had no measurable receptive field. Thus, our method allows unprecedented access to the complete neural representation of visual information, a crucial step for the understanding of population coding in sensory systems.
A Pathway in the Brainstem for Roll-Tilt of the Subjective Visual Vertical: Evidence from a Lesion–Behavior Mapping Study
Authors: Baier Bernhard , Thömke Frank , Wilting Janine , Heinze Caroline , Geber Christian , Dieterich Marianne
Published: October 2012

The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion–behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions of the medial longitudinal fasciculus (MLF) and the medial vestibular nucleus are associated with ipsiversive tilt of the SVV, whereas contraversive tilts are associated with lesions affecting the rostral interstitial nucleus of the MLF, the superior cerebellar peduncle, the oculomotor nucleus, and the interstitial nucleus of Cajal. Thus, these structures constitute the anatomical pathway in the brainstem for verticality perception. Present data indicate that graviceptive otolith signals present a predominant role in the multisensory system of verticality perception.
Emergence of Selectivity and Tolerance in the Avian Auditory Cortex
Authors: Meliza C. Daniel , Margoliash Daniel
Published: October 2012

The ability to recognize auditory objects like words and bird songs is thought to depend on neural responses that are selective between categories of the objects and tolerant of variation within those categories. To determine whether a hierarchy of increasing selectivity and tolerance exists in the avian auditory system, we trained European starlings (Sturnus vulgaris) to differentially recognize sets of songs, then measured extracellular single unit responses under urethane anesthesia in six areas of the auditory cortex. Responses were analyzed with a novel, generalized linear mixed model that provides robust estimates of the variance in responses to different stimuli. There were significant differences between areas in selectivity, tolerance, and the effects of training. The L2b and L1 subdivisions of field L had the least selectivity and tolerance. The caudal nidopallium (NCM) and subdivision L3 of field L were more selective than other areas, whereas the medial and lateral caudal mesopallium were more tolerant than NCM or L2b. L3 had a multimodal distribution of tolerance. Sensitivity to songs that were familiar and those that were not also distinguished the responses of caudomedial mesopallium and NCM. There were significant differences across areas between neurons with wide and narrow spikes. Collectively these results do not fit the traditional hierarchical view of the avian auditory forebrain, but are consistent with emerging concepts homologizing avian cortical and neocortical circuitry. The results suggest a functional divergence within the cortex into processing streams that respond to complementary aspects of the variability in communicative sounds.
Presynaptic α4β2 Nicotinic Acetylcholine Receptors Increase Glutamate Release and Serotonin Neuron Excitability in the Dorsal Raphe Nucleus
Authors: Garduño Julieta , Galindo-Charles Luis , Jiménez-Rodríguez Javier , Galarraga Elvira , Tapia Dagoberto , Mihailescu Stefan , Hernandez-Lopez Salvador
Published: October 2012

Several behavioral effects of nicotine are mediated by changes in serotonin (5-HT) release in brain areas that receive serotonergic afferents from the dorsal raphe nucleus (DRN).In vitroexperiments have demonstrated that nicotine increases the firing activity in the majority of DRN 5-HT neurons and that DRN contains nicotinic acetylcholine receptors (nAChRs) located at both somata and presynaptic elements. One of the most common presynaptic effects of nicotine is to increase glutamate release. Although DRN receives profuse glutamatergic afferents, the effect of nicotine on glutamate release in the DRN has not been studied in detail. Using whole-cell recording techniques, we investigated the effects of nicotine on the glutamatergic input to 5-HT DRN neurons in rat midbrain slices. Low nicotine concentrations, in the presence of bicuculline and tetrodotoxin (TTX), increased the frequency but did not change the amplitude of glutamate-induced EPSCs, recorded from identified 5-HT neurons. Nicotine-induced increase of glutamatergic EPSC frequency persisted 10–20 min after drug withdrawal. This nicotinic effect was mimicked by exogenous administration of acetylcholine (ACh) or inhibition of ACh metabolism. In addition, the nicotine-induced increase in EPSC frequency was abolished by blockade of α4β2 nAChRs, voltage-gated calcium channels, or intracellular calcium signaling but not by α7 nAChR antagonists. These data suggest that both nicotine and endogenous ACh can increase glutamate release through activation of presynaptic α4β2 but not α7 nAChRs in the DRN. The effect involves long-term changes in synaptic function, and it is dependent on voltage-gated calcium channels and presynaptic calcium stores.