bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 4‐phenylbutyrate therapy in a preterm infant with cholestasis and liver fibrosis
Authors: Ito Shogo , Hayashi Hisamitsu , Sugiura Tokio , Ito Koichi , Ueda Hiroko , Togawa Takao , Endo Takeshi , Tanikawa Ken , Kage Masayoshi , Kusuhara Hiroyuki , Saitoh Shinji
Published: February 2016

The bile salt export pump is expressed at the canalicular membrane of hepatocytes and mediates biliary excretion of bile salts. 4‐Phenylbutyrate (4 PB), a drug used to treat ornithine transcarbamylase deficiency, has been found to increase the hepatocanalicular expression of bile salt export pump. The beneficial effects of 4‐phenylbutyrate therapy have been reported for patients with progressive familial intrahepatic cholestasis, an inherited autosomal recessive liver disease. This is the first study to show the therapeutic effect of 4 PB in a preterm infant with cholestasis and liver fibrosis. The preterm infant had severe cholestasis with jaundice and failure to thrive refractory to ursodeoxycholic acid. Histology indicated giant cell hepatitis, cholestasis, and severe fibrosis. Bile salt export pump immunostaining showed lower expression than in a control. Oral 4 PB was started at a daily dose of 200 mg/kg/day. After the start of 4 PB therapy, cholestasis improved.
Engineered Tug‐of‐War Between Kinesin and Dynein Controls Direction of Microtubule Based Transport In Vivo
Authors: Rezaul Karim , Gupta Dipika , Semenova Irina , Ikeda Kazuho , Kraikivski Pavel , Yu Ji , Cowan Ann , Zaliapin Ilya , Rodionov Vladimir
Published: February 2016

Bidirectional transport of membrane organelles along microtubules (MTs) is driven by plus‐end directed kinesins and minus‐end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT‐based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug‐of‐war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug‐of‐war between opposing MT motors alone, by attaching a large number of kinesin‐1 motors to organelles transported by dynein to minus‐ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus‐end‐directed dynein‐dependent MT runs, leading to a reversal of the overall direction of dynein‐driven organelles in vivo. Therefore, in the absence of external regulators tug‐of‐war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo.
Erythrophagocytosis by plasmacytoid dendritic cells and monocytes is enhanced during inflammation
Authors: Richards Amanda L. , Hendrickson Jeanne E. , Zimring James C. , Hudson Krystalyn E.
Published: February 2016

BACKGROUND

Generation of antibodies against red blood cell (RBC) antigens can be a clinically significant problem. The underlying mechanisms that regulate the production of RBC antibodies are only partially understood; however, factors such as inflammation significantly increase the rates of RBC antibody generation. Humoral alloimmunization begins with consumption of transfused RBCs by antigen‐presenting cells (APCs). Recently, it has become appreciated that there are multiple different types of APCs. The relative contribution of APC subsets to RBC antibodies has not been described in either the quiescent or the inflamed states.

STUDY DESIGN AND METHODS

To evaluate the types of APCs that consume RBCs, and how inflammation affects this process, C56Bl/6 mice were treated with polyinosinic‐polycytidylic acid (poly(I:C)) to induce an inflammatory response and/or were transfused with 3,3′‐dihexadecyloxacarbocyanine perchlorate–labeled syngeneic RBCs. Erythrophagocytosis (both at baseline and during inflammation) was analyzed for different subsets of macrophages (MΦ), dendritic cells (DCs), B cells, and monocytes, by a combined approach using flow cytometry and fluorescent microscopy technology.

RESULTS

In four independent experiments, erythrophagocytosis at baseline was predominately performed by red pulp MΦ; however, during inflammation both plasmacytoid DCs (pDCs) and monocytes increased RBC consumption. Furthermore, pDCs up regulated MHC‐II and activation markers CD80 and CD86. In addition to changing patterns of erythrophagocytosis, inflammation also led to a significant decrease in CD11c+ conventional DC populations and an increase in granulocytes.

CONCLUSIONS

The nature of APCs that consume transfused RBCs is changed by inflammation. Given that APCs initiate humoral immune responses, these findings provide potential mechanistic insight into how inflammation regulates RBC alloimmunization.
Spinal inhibition and motor function in adults with spastic cerebral palsy
Authors: Condliffe E. G. , Jeffery D. T. , Emery D. J. , Gorassini M. A.
Published: February 2016

Key points

Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy.

Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction.

In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord.

In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants.

These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity.

Reduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post‐synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time‐locked to the occurrence of a sensory stimulation to produce peri‐stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF profile indicative of a pure excitatory post‐synaptic potential, with firing rates increasing above the mean pre‐stimulus rate for 300 ms or more. The amplitude of motoneuron inhibition during the period of IPSP activation, as measured from the surface EMG, was less in participants with poor motor function as evaluated with the Gross Motor Functional Classification System (r = 0.72, P < 0.001) and the Functional Mobility Scale (r = −0.82, P < 0.001). These findings demonstrate that in individuals with CP, reduced activation of motoneuron IPSPs by sensory inputs is associated with reduced motor function and may contribute to enhanced reflexes and spasticity in CP.
Design and Implementation of an Automated Gamma Probe for Jet Boring Uranium Mining
Authors: Niyongabo Kasmet T. , Nokleby Scott B.
Published: February 2016

A proof-of-concept detector prototype capable of collecting and storing radiometric data in the jet boring system (JBS) during pilot hole drilling at the Cigar Lake uranium mine is presented. Cigar Lake is the world’s second highest known grade uranium mine and is located in northern Saskatchewan, Canada. Variant design is used to design, develop, test, and implement the detector’s firmware, software, and hardware. The battery-powered detector is attached inside a JBS drill rod to collect radiometric data through the drilling cycle. A readout box is used to initiate the detector, recharge the battery, and download radiometric data after the pilot hole drilling cycle is complete. Functional testing results are presented, and comparative test results between the JBS gamma probe and the AlphaNUCLEAR Hi-Flux probe are evaluated. Field data collected from a pilot hole are plotted against the pilot hole’s driving layout and jetting recipe to show the accuracy of the readings collected.
Monte Carlo calculated correction factors for the PTW microDiamond detector in the Gamma Knife‐Model C
Authors: Barrett J. C. , Knill Cory
Published: February 2016

Purpose:

Accurate dose measurements in small fields require correction factors when sufficient CPE is not present inside of the field. These factors adjust for perturbation, volume averaging, and other effects; as such, they are field size, detector, and phantom dependent. In this work, Monte Carlo (MC) methods were used to calculate correction factors for PTW's microDiamond detector in Elekta's Gamma Knife Model‐C unit. These correction factors allow for accurate measurement of output factors—even in the smallest field sizes where CPE is not present.

Methods:

The small field correction factors were calculated as correction factors according to the Alfonso formalism. The MC model of the Gamma Knife was built with the EGSnrc code system, using BEAMnrc and DOSRZnrc user codes. Efforts were made to validate the MC model against experimental measurements. Using the model, field output factors and measurement ratios for each of the four helmet sizes were simulated for an ABS plastic phantom and validated against film measurements, detector measurements, and treatment planning system (TPS) data. Once validated against the available ABS phantom, the model was applied to a more waterlike solid water phantom. Using MC results from the solid water phantom, the final k correction factors were determined relative to the machine specific reference field—the 18 mm helmet, which is the largest field size available on the unit.

Results:

When validating against experimental measurements using the ABS phantom, all MC methods agreed with experiment within the stated uncertainties: MC determined field output factors agreed within 0.6% of the TPS and 1.4% of film; and MC simulated measurement ratios matched physically measured ratios within 1% for all helmet sizes. for the PTW microDiamond in the solid water phantom approached unity to within 0.4% ± 1.7% for all the helmet sizes except the 4 mm; the 4 mm helmet size over‐responded by 3.2% ± 1.7%, resulting in a of 0.969.

Conclusions:

Similar to what has been found in the Gamma Knife Perfexion, the PTW microDiamond over‐responds in the smallest 4 mm field. The over‐response can be corrected via the Alfonso formalism using the correction factors determined in this work. Using the MC calculated correction factors, the PTW microDiamond detector is an effective dosimeter in all available helmet sizes.
Postoperative 3D spine reconstruction by navigating partitioning manifolds
Authors: Kadoury Samuel , Labelle Hubert , Parent Stefan
Published: February 2016

Purpose:

The postoperative evaluation of scoliosis patients undergoing corrective treatment is an important task to assess the strategy of the spinal surgery. Using accurate 3D geometric models of the patient's spine is essential to measure longitudinal changes in the patient's anatomy. On the other hand, reconstructing the spine in 3D from postoperative radiographs is a challenging problem due to the presence of instrumentation (metallic rods and screws) occluding vertebrae on the spine.

Methods:

This paper describes the reconstruction problem by searching for the optimal model within a manifold space of articulated spines learned from a training dataset of pathological cases who underwent surgery. The manifold structure is implemented based on a multilevel manifold ensemble to structure the data, incorporating connections between nodes within a single manifold, in addition to connections between different multilevel manifolds, representing subregions with similar characteristics.

Results:

The reconstruction pipeline was evaluated on x‐ray datasets from both preoperative patients and patients with spinal surgery. By comparing the method to ground‐truth models, a 3D reconstruction accuracy of 2.24 ± 0.90 mm was obtained from 30 postoperative scoliotic patients, while handling patients with highly deformed spines.

Conclusions:

This paper illustrates how this manifold model can accurately identify similar spine models by navigating in the low‐dimensional space, as well as computing nonlinear charts within local neighborhoods of the embedded space during the testing phase. This technique allows postoperative follow‐ups of spinal surgery using personalized 3D spine models and assess surgical strategies for spinal deformities.
Clinical introduction of image lag correction for a cone beam CT system
Authors: Stankovic Uros , Ploeger Lennert S. , Sonke Jan‐Jakob , van Herk Marcel
Published: February 2016

Purpose:

Image lag in the flat‐panel detector used for Linac integrated cone beam computed tomography (CBCT) has a degrading effect on CBCT image quality. The most prominent visible artifact is the presence of bright semicircular structure in the transverse view of the scans, known also as radar artifact. Several correction strategies have been proposed, but until now the clinical introduction of such corrections remains unreported. In November 2013, the authors have clinically implemented a previously proposed image lag correction on all of their machines at their main site in Amsterdam. The purpose of this study was to retrospectively evaluate the effect of the correction on the quality of CBCT images and evaluate the required calibration frequency.

Methods:

Image lag was measured in five clinical CBCT systems (Elekta Synergy 4.6) using an in‐house developed beam interrupting device that stops the x‐ray beam midway through the data acquisition of an unattenuated beam for calibration. A triple exponential falling edge response was fitted to the measured data and used to correct image lag from projection images with an infinite response. This filter, including an extrapolation for saturated pixels, was incorporated in the authors' in‐house developed clinical cbct reconstruction software. To investigate the short‐term stability of the lag and associated parameters, a series of five image lag measurement over a period of three months was performed. For quantitative analysis, the authors have retrospectively selected ten patients treated in the pelvic region. The apparent contrast was quantified in polar coordinates for scans reconstructed using the parameters obtained from different dates with and without saturation handling.

Results:

Visually, the radar artifact was minimal in scans reconstructed using image lag correction especially when saturation handling was used. In patient imaging, there was a significant reduction of the apparent contrast from 43 ± 16.7 to 15.5 ± 11.9 HU without the saturation handling and to 9.6 ± 12.1 HU with the saturation handling, depending on the date of the calibration. The image lag correction parameters were stable over a period of 3 months. The computational load was increased by approximately 10%, not endangering the fast in‐line reconstruction.

Conclusions:

The lag correction was successfully implemented clinically and removed most image lag artifacts thus improving the image quality. Image lag correction parameters were stable for 3 months indicating low frequency of calibration requirements.
Technical Note: Method to correlate whole‐specimen histopathology of radical prostatectomy with diagnostic MR imaging
Authors: McGrath Deirdre M. , Lee Jenny , Foltz Warren D. , Samavati Navid , Jewett Michael A. S. , van der Kwast Theo , Chung Peter , Ménard Cynthia , Brock Kristy K.
Published: February 2016

Purpose:

Validation of MRI‐guided tumor boundary delineation for targeted prostate cancer therapy is achieved via correlation with gold‐standard histopathology of radical prostatectomy specimens. Challenges to accurate correlation include matching the pathology sectioning plane with the in vivo imaging slice plane and correction for the deformation that occurs between in vivo imaging and histology. A methodology is presented for matching of the histological sectioning angle and position to the in vivo imaging slices.

Methods:

Patients (n = 4) with biochemical failure following external beam radiotherapy underwent diagnostic MRI to confirm localized recurrence of prostate cancer, followed by salvage radical prostatectomy. High‐resolution 3‐D MRI of the ex vivo specimens was acquired to determine the pathology sectioning angle that best matched the in vivo imaging slice plane, using matching anatomical features and implanted fiducials. A novel sectioning device was developed to guide sectioning at the correct angle, and to assist the insertion of reference dye marks to aid in histopathology reconstruction.

Results:

The percentage difference in the positioning of the urethra in the ex vivo pathology sections compared to the positioning in in vivo images was reduced from 34% to 7% through slicing at the best match angle. Reference dye marks were generated, which were visible in ex vivo imaging, in the tissue sections before and after processing, and in histology sections.

Conclusions:

The method achieved an almost fivefold reduction in the slice‐matching error and is readily implementable in combination with standard MRI technology. The technique will be employed to generate datasets for correlation of whole‐specimen prostate histopathology with in vivo diagnostic MRI using 3‐D deformable registration, allowing assessment of the sensitivity and specificity of MRI parameters for prostate cancer. Although developed specifically for prostate, the method is readily adaptable to other types of whole tissue specimen, such as mastectomy or liver resection.
Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture
In Vitro
Authors: Murrell Isa , Wilkie Gavin S. , Davison Andrew J. , Statkute Evelina , Fielding Ceri A. , Tomasec Peter , Wilkinson Gavin W. G. , Stanton Richard J.
Published: February 2016

Clinical human cytomegalovirus (HCMV) strains invariably mutate when propagated
in vitro
. Mutations in gene RL13 are selected in all cell types, whereas in fibroblasts mutants in the UL128 locus (UL128L; genes UL128, UL130, and UL131A) are also selected. In addition, sporadic mutations are selected elsewhere in the genome in all cell types. We sought to investigate conditions under which HCMV can be propagated without incurring genetic defects. Bacterial artificial chromosomes (BACs) provide a stable, genetically defined source of viral genome. Viruses were generated from BACs containing the genomes of strains TR, TB40, FIX, and Merlin, as well as from Merlin-BAC recombinants containing variant nucleotides in UL128L from TB40-BAC4 or FIX-BAC. Propagation of viruses derived from TR-BAC, TB40-BAC4, and FIX-BAC in either fibroblast or epithelial cells was associated with the generation of defects around the prokaryotic vector, which is retained in the unique short (U
S
) region of viruses. This was not observed for Merlin-BAC, from which the vector is excised in derived viruses; however, propagation in epithelial cells was consistently associated with mutations in the unique long
b
′ (U
L
/
b
′) region, all impacting on gene UL141. Viruses derived from Merlin-BAC in fibroblasts had mutations in UL128L, but mutations occurred less frequently with recombinants containing UL128L nucleotides from TB40-BAC4 or FIX-BAC. Viruses derived from a Merlin-BAC derivative in which RL13 and UL128L were either mutated or repressed were remarkably stable in fibroblasts. Thus, HCMV containing a wild-type gene complement can be generated
in vitro
by deriving virus from a self-excising BAC in fibroblasts and repressing RL13 and UL128L.

IMPORTANCE
Researchers should aim to study viruses that accurately represent the causative agents of disease. This is problematic for HCMV because clinical strains mutate rapidly when propagated
in vitro
, becoming less cell associated, altered in tropism, more susceptible to natural killer cells, and less pathogenic. Following isolation from clinical material, HCMV genomes can be stabilized by cloning into bacterial artificial chromosomes (BACs), and then virus is regenerated by DNA transfection. However, mutations can occur not only during isolation prior to BAC cloning but also when virus is regenerated. We have identified conditions under which BAC-derived viruses containing an intact, wild-type genome can be propagated
in vitro
with minimal risk of mutants being selected, enabling studies of viruses expressing the gene complement of a clinical strain. However, even under these optimized conditions, sporadic mutations can occur, highlighting the advisability of sequencing the HCMV stocks used in experiments.
Hepatitis B Virus Capsids Have Diverse Structural Responses to Small-Molecule Ligands Bound to the Heteroaryldihydropyrimidine Pocket
Authors: Venkatakrishnan Balasubramanian , Katen Sarah P. , Francis Samson , Chirapu Srinivas , Finn M. G. , Zlotnick Adam
Published: February 2016

Though the hepatitis B virus (HBV) core protein is an important participant in many aspects of the viral life cycle, its best-characterized activity is self-assembly into 240-monomer capsids. Small molecules that target core protein (core protein allosteric modulators [CpAMs]) represent a promising antiviral strategy. To better understand the structural basis of the CpAM mechanism, we determined the crystal structure of the HBV capsid in complex with HAP18. HAP18 accelerates assembly, increases protein-protein association more than 100-fold, and induces assembly of nonicosahedral macrostructures. In a preformed capsid, HAP18 is found at quasiequivalent subunit-subunit interfaces. In a detailed comparison to the two other extant CpAM structures, we find that the HAP18-capsid structure presents a paradox. Whereas the two other structures expanded the capsid diameter by up to 10 Å, HAP18 caused only minor changes in quaternary structure and actually decreased the capsid diameter by ∼3 Å. These results indicate that CpAMs do not have a single allosteric effect on capsid structure. We suggest that HBV capsids present an ensemble of states that can be trapped by CpAMs, indicating a more complex basis for antiviral drug design.

IMPORTANCE
Hepatitis B virus core protein has multiple roles in the viral life cycle—assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions—making it an attractive antiviral target. Core protein allosteric modulators (CpAMs) are an experimental class of antivirals that bind core protein. The most recognized CpAM activity is that they accelerate core protein assembly and strengthen interactions between subunits. In this study, we observe that the CpAM-binding pocket has multiple conformations. We compare structures of capsids cocrystallized with different CpAMs and find that they also affect quaternary structure in different ways. These results suggest that the capsid “breathes” and is trapped in different states by the drug and crystallization. Understanding that the capsid is a moving target will aid drug design and improve our understanding of HBV interaction with its environment.
αvβ3 Integrin Boosts the Innate Immune Response Elicited in Epithelial Cells through Plasma Membrane and Endosomal Toll-Like Receptors
Authors: Casiraghi Costanza , Gianni Tatiana , Campadelli-Fiume Gabriella
Published: February 2016

We report that αvβ3 integrin strongly affects the innate immune response in epithelial cells. αvβ3 integrin greatly increased the response elicited via plasma membrane Toll-like receptors (TLRs) by herpes simplex virus or bacterial ligands. The endosomal TLR3, not the cytosolic sensor interferon gamma-inducible protein 16 (IFI16), was also boosted by αvβ3 integrin. The boosting was exerted specifically by αvβ3 integrin but not by αvβ6 or αvβ8 integrin. Current and previous work indicates that integrin-TLR cooperation occurs in epithelial and monocytic cells. The TLR response should be considered an integrin-TLR response.
Immediate Effects of Acupuncture on Tongue Pressure Including Swallowing Reflex Latency in Parkinson's Disease
Authors: Fukuda Shimpei , Kuriyama Nagato , Tsuru Hiroyuki , Egawa Masato
Published: February 2016

Background

It is important to evaluate tongue function in terms of its clinical implications for swallowing ability. Motor dysfunction and loss of coordination of the tongue are frequently seen, and this influences the oral and pharyngeal phases of swallowing. The purpose of this pilot study was to evaluate the effect of a single acupuncture treatment for tongue pressure in Parkinson's disease.

Methods

A total of 13 patients, aged 57– 84 years, were recruited. Tongue pressure was measured using a tongue pressure manometer. Furthermore, swallowing reflex latency was measured in 3 of the 13 patients.

Results

Significant changes were seen after acupuncture in mean tongue pressure, which increased from 23.1 to 26.7 kPa (p<0.01). Reductions were seen after acupuncture in mean swallowing reflex latency (from 5.2 to 4.6 s for first saliva swallow; from 19.9 to 15.7 s for second saliva swallow; and from 10.4 to 5.7 s for third saliva swallow(s)).

Conclusions

Our study's findings suggest that acupuncture may be useful for improving oral cavity function, but further controlled trials are needed.
Acupuncture for Episodic Cluster Headache: A Trigeminal Approach
Authors: Hayhoe Simon
Published: February 2016

Following evidence that acupuncture is clinically feasible and cost-effective in the treatment of headache, the UK National Institute for Health and Care Excellence recommends acupuncture as prophylactic treatment for migraine and tension headache. There has thus been expectation that other forms of headache should benefit also. Unfortunately, acupuncture has not generally been successful for cluster headache. This may be due to acupuncturists approaching the problem as one of severe migraine. In fact, cluster headache is classed as a trigeminal autonomic cephalgia. In this case report, episodic cluster headache is treated in the same way as has been shown effective for trigeminal neuralgia. Acupuncture is applied to the contralateral side at points appropriate for stimulating branches of the trigeminal nerve. Thus, ST2 is used for the infraorbital nerve, BL2 and Yuyao for the supratrochlear and supraorbital nerves, and Taiyang for the temporal branch of the zygomatic nerve.
Assessment of a non-invasive haemoglobin sensor NBM 200 among pregnant women in rural India
Authors: Ahankari A S , Fogarty A W , Tata L J , Dixit J V , Myles P R
Published: February 2016

Objective

This study aimed to assess a non-invasive haemoglobin (Hb) sensor NBM 200 in pregnant women in a rural Indian setting.

Methods

The study population consisted of women between 3 and 5 months of pregnancy, from 33 villages in Tuljapur and Lohara blocks of Osmanabad district, Maharashtra, between April 2014 and June 2015. Hb measurements obtained from the non-invasive sensor NBM 200 were compared with measurements obtained from an automated haematology analyser Sysmex XP-100, using the Bland Altman method and Spearman's Rank correlation coefficient. Interclass correlation coefficient (ICC), sensitivity and specificity values were used to assess the anaemia diagnostic accuracy of NBM 200 against the gold standard (Sysmex XP-100).

Results

Data were obtained from 269 pregnant women (median age: 21 years, IQR: 19–23 years). Hb levels estimated by the Sysmex XP-100 analyser ranged from 5.5 g/dL to 14.1 g/dL (mean: 10.0 g/dL, SD: 1.28), while measurements obtained from NBM 200 ranged from 9.5 g/dL to 14.6 g/dL (mean: 11.9 g/dL, SD: 1.43). Spearman's test found a significant, moderately positive correlation between the two methods (rs=0.4, p<0.001), ICC was 0.22, and the Bland-Altman analysis showed a mean difference of −1.8 g/dL (95% CI −2.06 to −1.71), indicating a systematic overestimation of Hb using the NBM 200. The NBM 200 showed low sensitivity (33.7%; 95% CI 27.3% to 40.5%) but high specificity (91.8%; 95% CI 81.9% to 97.3%) for the diagnosis of anaemia.

Conclusions

Hb measurements obtained from the NBM 200 were higher with consequent underestimation of anaemia as compared with the gold standard reference method. This limits the use of the NBM 200 as an anaemia diagnostic test in our study population consisting of women during pregnancy.
Comments on the dilemma in the January issue: ‘When in Rome. . . ’
Authors: McCulloch Steven
Published: February 2016

In the dilemma discussed in the January issue of In Practice, you were working on a short stint for a charity NGO in a developing country. A farmer had walked in with a 13‐week‐old dobermann puppy and had asked you to clip its ears and dock its tail. You were not comfortable with this, but the farmer said he would do it himself if you did not. Also, a local vet had offered to do it for you, if you would help with the anaesthesia (IP, January 2016, vol 38, pp 46‐47). Richard Brown suggested that this was not an urgent matter, and time should be taken to assess the situation. You needed to look at the law in the country, what local veterinary colleagues would do, the local standards of welfare, and the capability of the farmer before making any decision. Even though it might be against your own ethical stance, on welfare grounds the best option might be to carry out the procedure yourself with high‐quality care. As in any situation, prevention was better than cure: before working abroad you should do some research to provide yourself with information on the kinds of situations that might arise.
Equine distal limb diagnostic anaesthesia: (1) Basic principles and perineural techniques
Authors: Barker Will
Published: February 2016

Despite technological advances in diagnostic imaging, diagnostic anaesthesia remains the cornerstone of lameness investigations in horses. It is often not possible to localise the source of lameness confidently on clinical history and examination alone, and there may be more than one site causing the problem. In such cases, a systematic approach should be adopted working from the foot in a proximal direction. If the initial history and clinical examination raise suspicion of a particular site as the source of lameness, a targeted approach can be used to improve the efficiency of the process and reduce the number of injections required. This article, the first in a two‐part series, reviews the basic principles involved in diagnostic anaesthesia and the various perineural techniques performed in the distal limb. The second article, to be published in a subsequent issue of In Practice, will cover intrasynovial anaesthesia of the distal limb.
Video training with peer feedback in real-time consultation: acceptability and feasibility in a general-practice setting
Authors: Eeckhout Thomas , Gerits Michiel , Bouquillon Dries , Schoenmakers Birgitte
Published: February 2016

Objective

Since many years, teaching and training in communication skills are cornerstones in the medical education curriculum. Although video recording in a real-time consultation is expected to positively contribute to the learning process, research on this topic is scarce. This study will focus on the feasibility and acceptability of video recording during real-time patient encounters performed by general practitioner (GP) trainees.

Method

The primary research question addressed the experiences (defined as feasibility and acceptability) of GP trainees in video-recorded vocational training in a general practice. The second research question addressed the appraisal of this training. The procedure of video-recorded training is developed, refined and validated by the Academic Teaching Practice of Leuven since 1974 (Faculty of Medicine of the University of Leuven). The study is set up as a cross-sectional survey without follow-up. Outcome measures were defined as ‘feasibility and acceptability’ (experiences of trainees) of the video-recorded training and were approached by a structured questionnaire with the opportunity to add free text comments. The studied sample consisted of all first-phase trainees of the GP Master 2011–2012 at the University of Leuven.

Results

Almost 70% of the trainees were positive about recording consultations. Nevertheless, over 60% believed that patients felt uncomfortable during the video-recorded encounter. Almost 90% noticed an improvement of own communication skills through the observation and evaluation of. Most students (85%) experienced the logistical issues as major barrier to perform video consultations on a regular base.

Conclusions

This study lays the foundation stone for further exploration of the video training in real-time consultations. Both students and teachers on the field acknowledge that the power of imaging is underestimated in the training of communication and vocational skills. The development of supportive material and protocols will lower thresholds.

Practice implications

Time investment for teachers could be tempered by bringing up students to peer tutors and by an accurate scheduling of the video training. The development of supportive material and protocols will lower thresholds. Further research should finally focus on long-term efficacy and efficiency in terms of learning outcomes and on the facilitation of the technical process.
Galactose-amidine derivatives as selective antagonists of galectin-9
Authors: Mandal Santanu , Rajput Vishal K. , Sundin Anders P. , Leffler Hakon , Mukhopadhyay Balaram , Nilsson Ulf J.
Published: February 2016

The family of galectin proteins involved in adhesion, growth regulation, immunity, and inflammatory events are important targets for development of small molecule antagonists. Here, N-sulfonyl amidine galactopyranoside derivatives obtained via a multicomponent reaction between galactose alkyne derivatives, sulfonyl azides, and amines were evaluated as antagonists of galectin-1, -2, -3, -4N (N-terminal domain), -4C (C-terminal domain), -8N, -9N, and -9C in a competitive fluorescence polarization assay. Highly selective compounds against galectin-9N with up to 30-fold improved affinity compared to the reference methyl β-d-galactopyranoside were identified. Molecular dynamics simulation suggested that the selectivity and affinity for galectin-9N originate from the N-sulfonyl amidine moieties forming tridentate hydrogen bonds to two asparagine side chains and one phenyl stacking edge-to-face to an arginine side chain. These selective galectin-9N antagonists are of significant value as chemical tools for studying galectin-9 biology and chemistry as well as possible starting structures for the discovery of galectin-9-targeting drugs influencing, e.g., immune regulation.
Regge trajectories of exotic hadrons in the flux tube model
Authors: Nandan Hemwati , Ranjan Akhilesh
Published: February 2016

We have investigated the Regge trajectories of exotic hadrons by considering different possible pentaquark configurations with finite quark mass in the flux tube model. Significant deviation is observed in the linear behavior of the Regge trajectories for pentaquark systems in view of the universal value of the Regge slope parameter for hadrons. The modified Regge trajectories are also compared with the available experimental and lattice data. It is observed that the nonlinear Regge trajectories of such pentaquark systems can be well described by the relativistic corrections in view of the current quark masses and the high rotational speed of the quarks at the end of flux tube structure.
Failure of the Feynman R1 gauge for the standard model: An explicit example
Authors: Wu Tai Tsun , Wu Sau Lan
Published: February 2016

The decay of the Higgs particle into two photons through a [Formula: see text] loop was calculated in a straightforward way four years ago on the basis of the standard model. This calculation was carried out in the unitary gauge. Nevertheless, all attempts to reproduce this correct answer using the Feynman rules in the [Formula: see text] gauge, or the more general [Formula: see text] gauge, have failed. In this paper, a detailed analysis is carried out to compare the unitary gauge with the [Formula: see text] gauge; through this comparison, the underlying reason is determined why the answer cannot be obtained using the Feynman rules in the [Formula: see text] gauge.

This is the first example where the use of the Feynman rules in the [Formula: see text] gauge leads to an incorrect answer, and this incorrect answer cannot be ruled out by any simple argument such as gauge invariance. It means that great care must be exercised in using Feynman rules.
Biosynthesis of the Metalloclusters of Nitrogenases
Authors: Hu Yilin , Ribbe Markus W.
Published: February 2016

Nitrogenase is a versatile metalloenzyme that is capable of catalyzing two important reactions under ambient conditions: the reduction of nitrogen (N2) to ammonia (NH3), a key step in the global nitrogen cycle; and the reduction of carbon monoxide (CO) and carbon dioxide (CO2) to hydrocarbons, two reactions useful for recycling carbon waste into carbon fuel. The molybdenum (Mo)- and vanadium (V)-nitrogenases are two homologous members of this enzyme family. Each of them contains a P-cluster and a cofactor, two high-nuclearity metalloclusters that have crucial roles in catalysis. This review summarizes the progress that has been made in elucidating the biosynthetic mechanisms of the P-cluster and cofactor species of nitrogenase, focusing on what is known about the assembly mechanisms of the two metalloclusters in Mo-nitrogenase and giving a brief account of the possible assembly schemes of their counterparts in V-nitrogenase, which are derived from the homology between the two nitrogenases.
Perspectives on Additive Manufacturing
Authors: Bourell David L.
Published: February 2016

Additive manufacturing (AM) has skyrocketed in visibility commercially and in the public sector. This article describes the development of this field from early layered manufacturing approaches of photosculpture, topography, and material deposition. Certain precursors to modern AM processes are also briefly described. The growth of the field over the last 30 years is presented. Included is the standard delineation of AM technologies into seven broad categories. The economics of AM part generation is considered, and the impacts of the economics on application sectors are described. On the basis of current trends, the future outlook will include a convergence of AM fabricators, mass-produced AM fabricators, enabling of topology optimization designs, and specialization in the AM legal arena. Long-term developments with huge impact are organ printing and volume-based printing.
American Exceptionalism and the Welfare State: The Revisionist Literature
Authors: Prasad Monica
Published: February 2016

Recent research has argued that the American welfare state is not necessarily smaller than the welfare state in other advanced industrial countries. Rather, it is organized on principles that make it seem smaller: Because it functions through tax expenditures and public–private partnerships, it is less visible than welfare states that operate on the principle of direct spending. This review summarizes the most important messages of this revisionist scholarship, particularly in how this form of welfare provision undermines support for the welfare state, increases the complexity and decreases the efficiency of the system, and hides regressive policies from public scrutiny. I then argue that although this work has taught us much about American politics, several gaps need to be addressed. First, the explanation of the origins of this state of affairs is incomplete and unconvincing. Second, while private welfare is an important part of the American experience, the scholarship on private welfare provision has not yet grappled with the fact that private welfare was also historically found in many other advanced industrial countries, but did not crowd out the public welfare state there as it has in the United States. Finally, although the scholarship has usefully called attention to the invisibility of tax expenditures, we should not consider tax expenditures part of the “welfare state,” because they only rarely accomplish the functions of redistribution and risk pooling of public welfare programs. Rather, in most cases, tax expenditures should be seen as tax cuts, that is, diminishment of state capacity. These observations suggest that the scholarship would benefit from broader engagement with the comparative literature on political economy and from a more precise and conceptually grounded definition of the “welfare state.”
Proton channels and renal hypertensive injury: a key piece of the Dahl salt-sensitive rat puzzle?
Authors: O'Connor Paul M. , Guha Avirup , Stilphen Carly A. , Sun Jingping , Jin Chunhua
Published: February 2016

Hv1 is a voltage-gated proton channel highly expressed in phagocytic cells, where it participates in the NADPH oxidase-dependent respiratory burst. We have recently identified Hv1 as a novel renal channel, expressed in the renal medullary thick ascending limb that appears to importantly contribute to the pathogenesis of renal hypertensive injury in the Dahl salt-sensitive rat model. The purpose of this review is to describe the experimental approaches that we have undertaken to identify the source of excess reactive oxygen species production in the renal outer medulla of Dahl salt-sensitive rats and the resulting evidence that the voltage-gated proton channel Hv1 mediates augmented superoxide production and contributes to renal medullary oxidative stress and renal injury. In addition, we will attempt to point out areas of current controversy, as well as propose areas in which further experimental studies are likely to move the field forward. The content of the following review was presented as part of the Water and Electrolyte Homeostasis Section New Investigator Award talk at Experimental Biology 2014.
Neural correlates of behavioral amplitude modulation sensitivity in the budgerigar midbrain
Authors: Henry Kenneth S. , Neilans Erikson G. , Abrams Kristina S. , Idrobo Fabio , Carney Laurel H.
Published: February 2016

Amplitude modulation (AM) is a crucial feature of many communication signals, including speech. Whereas average discharge rates in the auditory midbrain correlate with behavioral AM sensitivity in rabbits, the neural bases of AM sensitivity in species with human-like behavioral acuity are unexplored. Here, we used parallel behavioral and neurophysiological experiments to explore the neural (midbrain) bases of AM perception in an avian speech mimic, the budgerigar ( Melopsittacus undulatus). Behavioral AM sensitivity was quantified using operant conditioning procedures. Neural AM sensitivity was studied using chronically implanted microelectrodes in awake, unrestrained birds. Average discharge rates of multiunit recording sites in the budgerigar midbrain were insufficient to explain behavioral sensitivity to modulation frequencies <100 Hz for both tone- and noise-carrier stimuli, even with optimal pooling of information across recording sites. Neural envelope synchrony, in contrast, could explain behavioral performance for both carrier types across the full range of modulation frequencies studied (16–512 Hz). The results suggest that envelope synchrony in the budgerigar midbrain may underlie behavioral sensitivity to AM. Behavioral AM sensitivity based on synchrony in the budgerigar, which contrasts with rate-correlated behavioral performance in rabbits, raises the possibility that envelope synchrony, rather than average discharge rate, might also underlie AM perception in other species with sensitive AM detection abilities, including humans. These results highlight the importance of synchrony coding of envelope structure in the inferior colliculus. Furthermore, they underscore potential benefits of devices (e.g., midbrain implants) that evoke robust neural synchrony.
Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy
Authors: Hartmann Kerstin , Koenen Mascha , Schauer Sebastian , Wittig-Blaich Stephanie , Ahmad Mubashir , Baschant Ulrike , Tuckermann Jan P.
Published: February 2016

Cartilage and bone are severely affected by glucocorticoids (GCs), steroid hormones that are frequently used to treat inflammatory diseases. Major complications associated with long-term steroid therapy include impairment of cartilaginous bone growth and GC-induced osteoporosis. Particularly in arthritis, GC application can increase joint and bone damage. Contrarily, endogenous GC release supports cartilage and bone integrity. In the last decade, substantial progress in the understanding of the molecular mechanisms of GC action has been gained through genome-wide binding studies of the GC receptor. These genomic approaches have revolutionized our understanding of gene regulation by ligand-induced transcription factors in general. Furthermore, specific inactivation of GC signaling and the GC receptor in bone and cartilage cells of rodent models has enabled the cell-specific effects of GCs in normal tissue homeostasis, inflammatory bone diseases, and GC-induced osteoporosis to be dissected. In this review, we summarize the current view of GC action in cartilage and bone. We further discuss future research directions in the context of new concepts for optimized steroid therapies with less detrimental effects on bone.
Habitat Ecology and Ichthyofaunal Diversity of Two Creeks and Their Associated Streams from Port Blair, South Andaman Islands
Authors: Kumar M. Arun , Venu S. , Padmavati G.
Published: February 2016

Habitat ecology and ichthyofaunal diversity were analyzed from two creeks and their associated streams in Port Blair: one was perennial and the other one was seasonal. Various habitat types like riffles, pools, and major and minor bends in both streams were studied. The perennial stream has 12 riffles and 14 pools from head point to the entering point of the creek. The seasonal stream has 15 riffles and 13 pools from the starting point to the sink. The perennial stream was found to have higher ichthyofaunal diversity than the seasonal stream: 1701 individuals constituting 8 orders, 30 families, 42 genera, and 54 species were recorded. Among these, 395 specimens represented by 21 species were found in perennial stream, 291 specimens with 11 species were found in seasonal stream, 863 specimens by 48 species were noted in creek, and 152 specimens constituting 14 species in sink were recorded. The physicochemical parameters of the habitats showed more or less a similar trend. The average dissolved oxygen value of the perennial stream was higher than that of the seasonal stream. Higher temperature values were noted during the postmonsoon season. This study has indicated a wide lacuna in the knowledge of the fresh water habitats and their inhabitants on these islands.