bluuebunny/crossref_metadata_2025 huggingface dataset:
An exon skipping in a SEPALLATA‐Like gene is associated with perturbed floral and fruits development in cucumber
Authors: Wang Xin , Gao Dongli , Sun Jinjing , Liu Min , Lun Yaoyao , Zheng Jianshu , Wang Shenhao , Cui Qingzhi , Wang Xiaofeng , Huang Sanwen
Published: March 2016

We isolated a mutant showing perturbations in the development of male and female floral organs and fruits. Analysis of the single nucleotide polymorphisms from bulked F2 pools identified the causative variant occurring in Csa4G126690. Csa4G126690 shows high homology to Arabidopsis SEPALLATA2 (SEP2) thus being designated CsSEP2. The causative variant was located on the splicing site of CsSEP2, resulting in the skipping of exon 6 and abolishment of the transcriptional activity. Our data suggest that CsSEP2 is involved in the floral organ and fruits development by conferring transcriptional activity.
Cryogenic transmission electron microscopy study: preparation of vesicular dispersions by quenching microemulsions
Authors: LEE H.S. , MORRISON E.D. , ZHANG Q. , MCCORMICK A.V.
Published: March 2016

We previously showed that long‐lived nanoemulsions, seeming initially vesicular, might be prepared simply by diluting and cooling (quenching) warm microemulsions with n‐hexadecane with precooled water. In this paper, we confirm that these systems are vesicular dispersions when fresh, and they can be made with similar structures and compositional dependence using alkanes with chain lengths ranging from octane to hexadecane. The nanostructures of fresh nanoemulsions are imaged with cryogenic transmission electron microscopy (cryo‐TEM). We confirm that water‐continuous microemulsions give simple dispersions of vesicles (sometimes unilamellar), typically less than 100 nm in diameter; these systems can avoid separation for over 2 months. Selected samples were also prepared using halogenated alkanes to create additional contrast in the cryo‐TEM, allowing us to confirm that the oil is located in the observed vesicular structures.
Treatment and prognosis of bone metastasis from cervical cancer (KCOG‐G1202s)
Authors: Makino Hiroshi , Nishio Shin , Tsubamoto Hiroshi , Shimada Muneaki , Nishikawa Ryutaro , Kai Kentaro , Ito Kimihiko , Mizuno Tomoko , Ushijima Kimio , Morishige Ken‐ichiro
Published: March 2016

Aim

The early and precise diagnosis and proper palliative treatment of bone metastasis is important for improving the quality of life of cervical cancer patients. The aim of this study was to clarify the clinical features, treatment modalities and prognosis of bone metastasis in cervical cancer patients in Japan.

Methods

The medical records of 75 cervical cancer patients with bone metastasis who were treated between January 2000 and December 2010 were retrospectively analyzed in a multi‐institutional study.

Results

Fifty‐four patients (72.0%) had a single bone metastasis. Bone metastases were found in the spine (46.7%) and pelvis (42.7%). Forty‐three patients (57.3%) also had extra‐osseous metastases. Most of the patients received radiotherapy, chemotherapy or both, but 25 patients (33.3%) received palliative care only. Bisphosphonates were given as palliative therapy to 25 patients (33.3%). The median overall survival after the diagnosis of bone metastasis was significantly shorter in patients with extra‐osseous metastases than in those without extra‐osseous metastases (14 vs 5 months; P < 0.05). The survival of patients who received chemotherapy following radiotherapy or concurrent chemoradiotherapy was significantly longer than that of the patients who received palliative care. On multivariate analysis, the presence of extra‐osseous metastasis was an independent predictor of survival in patients with bone metastasis from cervical cancer.

Conclusions

Multidisciplinary treatment might improve the prognosis of patients with bone metastasis who do not have extra‐osseous lesions.
Phylogenetic relationships of corallinaceae (Corallinales, Rhodophyta): taxonomic implications for reef‐building corallines
Authors: Rösler Anja , Perfectti Francisco , Peña Viviana , Braga Juan Carlos
Published: March 2016

A new, more complete, five‐marker (SSU, LSU, psbA, COI, 23S) molecular phylogeny of the family Corallinaceae, order Corallinales, shows a paraphyletic grouping of seven well‐supported monophyletic clades. The taxonomic implications included the amendment of two subfamilies, Neogoniolithoideae and Metagoniolithoideae, and the rejection of Porolithoideae as an independent subfamily. Metagoniolithoideae contained Harveylithon gen. nov., with H. rupestre comb. nov. as the generitype, and H. canariense stat. nov., H. munitum comb. nov., and H. samoënse comb. nov. Spongites and Pneophyllum belonged to separate clades. The subfamily Neogoniolithoideae included the generitype of Spongites, S. fruticulosus, for which an epitype was designated. Pneophyllum requires reassesment. The generitype of Hydrolithon, H. reinboldii, was a younger heterotypic synonym of H. boergesenii. The evolutionary novelty of the subfamilies Hydrolithoideae, Metagoniolithoideae, and Lithophylloideae was the development of tetra/bisporangial conceptacle roofs by filaments surrounding and interspersed among the sporangial initials.
Divergent homoeolog evolution of the anthocyanin regulatory gene R in Oryza allopolyploids
Authors: Bao Ying , Zhu Xiao‐Lin , Jing Xiang , Liu Mei
Published: March 2016

Polyploidization is an important evolutionary force in plant speciation and diversification. Retention and elimination of homoeologs derived by polyploidization are prevalent, whereas the evolutionary details of some duplicated genes in closely related natural polyploids are largely unknown. In the present study, we used an important regulatory gene (R) that encodes a bHLH protein in the anthocyanin metabolism pathway to demonstrate divergent evolutionary fates of homoeologs among four related Oryza allotetraploids. The BBCC genome species O. punctata Kotschy ex Steud. maintained both of its homoeologs, whereas three CCDD genome species (O. alta Swallen, O. grandiglumis (Döll) Prod., and O. latifolia Desv.) lost their C subgenome homoeologous copies. In addition, the evolutionary rates of the homoeologs in the polyploids were equivalent to their corresponding homologs in diploids. We also found a slightly higher level of nucleotide diversity in R for the C subgenome homoeolog than for the B subgenome counterpart in O. punctata. After comparing the two types of polyploids, we conclude that inconsistent evolutionary patterns of R in these polyploids are probably associated with different evolutionary time, asymmetrical subgenome evolutionary dynamics, and unique demographical characteristics of these species.
Long‐term Outcome of Irish Wolfhound Dogs with Preclinical Cardiomyopathy, Atrial Fibrillation, or Both Treated with Pimobendan, Benazepril Hydrochloride, or Methyldigoxin Monotherapy
Authors: Vollmar A.C. , Fox P.R.
Published: March 2016

Background

Dilated cardiomyopathy (DCM) is a common cause of morbidity and mortality in the Irish Wolfhound (IW). However, the benefit of medical treatment in IW dogs with preclinical DCM, atrial fibrillation (AF), or both has not been demonstrated.

Objectives

Compare the time to develop congestive heart failure (CHF) or sudden death in IW dogs with preclinical DCM, AF, or both receiving monotherapy with pimobendan, methyldigoxin, or benazepril hydrochloride.

Animals

Seventy‐five client‐owned IW dogs.

Methods

Irish Wolfhound dogs were prospectively randomized to receive pimobendan (Vetmedin®), benazepril HCl (Fortekor®), or methyldigoxin (Lanitop®) monotherapy in a 1:1:1 ratio in a blinded clinical trial. The prospectively defined composite primary endpoint was onset of CHF or sudden death. To assure stringent evaluation of treatment effect, data from dogs complying with the study protocol were analyzed.

Results

Sixty‐six IW fulfilling the study protocol included 39 males, 27 females; median (interquartile range) age, 4.0 years (3.0–5.0 years) and weight, 70.0 kg (63.0–75.0 kg). Primary endpoint was reached in 5 of 23 (21.7%) IW receiving pimobendan, 11 of 22 (50.0%) receiving benazepril HCl, and 9 of 21 (42.9%) receiving methyldigoxin. Median time to primary endpoint was significantly longer for pimobendan (1,991 days; 65.4 months) compared to methyldigoxin (1,263 days; 41.5 months; P = .031) or benazepril HCl‐(997 days; 32.8 months; P = .008) treated dogs.

Conclusions and Clinical Importance

In IW dogs with preclinical DCM, AF or both, pimobendan monotherapy significantly prolonged time to onset of CHF or sudden death than did monotherapy with benazepril HCl or methyldigoxin.
Language as Sensor in Human‐Centered Computing: Clinical Contexts as Use Cases
Authors: Alm Cecilia Ovesdotter
Published: March 2016

Recognizing the increased emphasis on adaptive and personalized computing, as well as the popularity of multimodal natural language and speech processing in human‐centered applications, this paper articulates and discusses the role of natural language as a rich and meaningful sensor of the human body and mind. As the primary means of human interaction, information sharing, and social, emotional, and interpersonal grounding, linguistic sensing provides a particularly useful and rich sensory window for understanding the dynamically and temporally unfolding state of the human body and mind for non‐linguistic aims. For sensory monitoring, linguistic data are unobtrusive, inexpensive, pervasive, natural, especially insightful from the perspective of cognitive processing, and generally convenient to capture, in contrast to many other sensor modalities that require excessive wearable equipment or smart clothing. Using clinical computational linguistics as a springboard for discussing and exemplifying this unconventional yet increasingly prevalent view of language, including its role in practical and serviceable linguistic analysis, this overview surveys recent work in computational linguistics that broadly takes advantage of linguistic sensing's potential. The discussion also outlines existing challenges and considerations for continued research in this area, from the perspective of natural language as a sensor in human‐centered computing and the development of innovative and applied language technologies.
The Phonological Representation of Affricates
Authors: Berns Janine
Published: March 2016

This article presents a picture of one specific category of sounds: ‘affricates’. These sounds, which we find for instance in the English words jazz or catch, combine the articulation of a plosive and a fricative. Affricates constitute a challenge for phonological theory, and their underlying representation has been subject to a series of revisions throughout the history of phonology: should the articulatory duality be reflected in the phonological representation? or are affricates rather some kind of plosive with something extra? or is the concept ‘affricate’ simply not relevant at all?

This paper provides a more or less chronological overview of the different analyses that have been proposed in phonological theory and illustrates the crucial arguments that have been put forward in favor of, or against, specific representations.
Relationship between tongue thickness and tongue pressure in neuromuscular disorders
Authors: Umemoto George , Furuya Hirokazu , Arahata Hajime , Sugahara Miwa , Sakai Mitsuaki , Tsuboi Yoshio
Published: March 2016

Background

Few previous studies have objectively evaluated the relationship between tongue volume and tongue weakness in patients with neuromuscular disorders.

Aim

The present study aimed to show the relationship between tongue thickness and tongue pressure in patients with neuromuscular disorders.

Methods

A total of 21 Duchenne muscular dystrophy patients, 30 myotonic dystrophy type 1 patients and 33 amyotrophic lateral sclerosis patients were recruited for this study. Tongue thickness was measured using ultrasonography, and defined as the distance from the raphe of the mylohyoid muscle to the tongue dorsum. Maximum tongue pressure was also determined using an oral probe whose small balloon was compressed onto the palate with the tongue.

Results

Tongue thickness was significantly higher in the Duchenne muscular dystrophy group than in the other groups. The maximum tongue pressure was lower in the myotonic dystrophy type 1 group than the DMD group. A significant correlation between tongue thickness and maximum tongue pressure was found in the amyotrophic lateral sclerosis group, but not in the other groups.

Conclusion

Ultrasound is an effective tool to assess tongue thickness in patients with neuromuscular disorders. The present results suggested that tongue pressure, which was relevant to tongue thickness, especially in amyotrophic lateral sclerosis patients, was more useful to evaluate swallowing function than kinesiological analysis of tongue movement.
Experimental Neospora Caninum Infection in Pregnant Dairy Heifers Raises Concentrations of Pregnancy‐Associated Glycoproteins 1 and 2 in Foetal Fluids
Authors: Mur‐Novales R , López‐Gatius F , Serrano‐Pérez B , García‐Ispierto I , Darwich L , Cabezón O , de Sousa NM , Beckers JF , Almería S
Published: March 2016

Contents

Plasma concentrations of PAG‐1 are used for pregnancy diagnosis and as a marker of placental/foetal well‐being, while those of PAG‐2 may be an indicator of abortion risk in Neospora caninum‐infected cows. Studies have shown that N. caninum infection modifies PAG‐1 and PAG‐2 patterns in maternal blood plasma. However, no prior work has examined the effects of N. caninum infection on concentrations of PAGs in foetal fluids. In this study, PAG‐1, PAG‐2 and pH levels were determined in the amniotic and allantoic fluids of foetuses collected at 152 days of gestation from control uninfected dams and from dams experimentally infected with N. caninum on Day 110 of gestation. Foetal fluids from infected foetuses had significantly higher PAG‐2 concentrations (p = 0.026) and pH values (p = 0.02) than fluids from non‐infected foetuses. In infected foetuses, significantly higher concentrations of PAG‐1 (p < 0.001) and PAG‐2 (p < 0.001) were detected in fluid samples showing antibodies against N. caninum than those without antibodies. Moreover, pH values were significantly higher (p = 0.011) in foetal fluid samples with antibodies than in samples from non‐infected foetuses. In conclusion, this is the first report on the effect of N. caninum infection on PAG levels in foetal fluids. Our results indicate that following the experimental infection of dams with N. caninum on Day 110 of gestation, foetal fluids collected from the infected foetuses of these dams featured higher PAG‐1 and PAG‐2 levels and pH values than fluids from non‐infected controls, provided that the samples tested showed the presence of antibodies. The clinical implications of these findings are that following infection with N. caninum, most cows will experience some level of placental damage and that this injury correlates with foetal fluid PAG levels and pH.
l‐carnitine Mediated Reduction in Oxidative Stress and Alteration in Transcript Level of Antioxidant Enzymes in Sheep Embryos Produced In Vitro
Authors: Mishra A , Reddy IJ , Gupta PSP , Mondal S
Published: March 2016

Contents

The objective of this study was to find out the effect of l‐carnitine on oocyte maturation and subsequent embryo development, with l‐carnitine‐mediated alteration if any in transcript level of antioxidant enzymes (GPx, Cu/Zn‐SOD (SOD1) and Mn‐SOD (SOD2) in oocytes and developing sheep embryos produced in vitro. Different concentrations of l‐carnitine (0 mm, 2.5 mm, 5 mm, 7.5 mm and 10 mm) were used in maturation medium. Oocytes matured with 10 mm l‐carnitine showed significantly (p < 0.05) higher cleavage (66.80% vs 39.66, 41.76, 44.64, 64.31%), morula (48.50% vs 20.88, 26.01, 26.99, 44.72%) and blastocyst (33.22% vs 7.66, 9.19, 10.71, 28.57%) percentage as compared to lower concentrations (0 mm, 2.5 mm, 5 mm and 7.5 mm). Cleavage percentage between 10 mm and 7.5 mm l‐carnitine were not significantly different. Maturation rate was not influenced by supplementation of any experimental concentration of l‐carnitine. There was a significant (p < 0.05) decrease in intracellular ROS and increase in intracellular GSH in 10 mm l‐carnitine‐treated oocytes and embryos than control group. Antioxidant effect of l‐carnitine was proved by culturing oocytes and embryos with H2O2 in the presence of l‐carnitine which could be able to protect oocytes and embryos from H2O2‐induced oxidative damage. l‐carnitine supplementation significantly (p < 0.05) upregulated the expression of GPx and downregulated the expression of SOD2 genes, whereas the expression pattern of SOD1 and GAPDH (housekeeping gene) genes was unaffected in oocytes and embryos. It was concluded from the study that l‐carnitine supplementation during in vitro maturation reduces oxidative stress‐induced embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH that in turn improved developmental potential of oocytes and embryos and alters transcript level of antioxidant enzymes.
Assessment of metal artifact reduction methods in pelvic CT
Authors: Abdoli Mehrsima , Mehranian Abolfazl , Ailianou Angeliki , Becker Minerva , Zaidi Habib
Published: March 2016

Purpose:

Metal artifact reduction (MAR) produces images with improved quality potentially leading to confident and reliable clinical diagnosis and therapy planning. In this work, the authors evaluate the performance of five MAR techniques for the assessment of computed tomography images of patients with hip prostheses.

Methods:

Five MAR algorithms were evaluated using simulation and clinical studies. The algorithms included one‐dimensional linear interpolation (LI) of the corrupted projection bins in the sinogram, two‐dimensional interpolation (2D), a normalized metal artifact reduction (NMAR) technique, a metal deletion technique, and a maximum a posteriori completion (MAPC) approach. The algorithms were applied to ten simulated datasets as well as 30 clinical studies of patients with metallic hip implants. Qualitative evaluations were performed by two blinded experienced radiologists who ranked overall artifact severity and pelvic organ recognition for each algorithm by assigning scores from zero to five (zero indicating totally obscured organs with no structures identifiable and five indicating recognition with high confidence).

Results:

Simulation studies revealed that 2D, NMAR, and MAPC techniques performed almost equally well in all regions. LI falls behind the other approaches in terms of reducing dark streaking artifacts as well as preserving unaffected regions (p < 0.05). Visual assessment of clinical datasets revealed the superiority of NMAR and MAPC in the evaluated pelvic organs and in terms of overall image quality.

Conclusions:

Overall, all methods, except LI, performed equally well in artifact‐free regions. Considering both clinical and simulation studies, 2D, NMAR, and MAPC seem to outperform the other techniques.
Eigenfunction approach to the Green's function parabolic equation in outdoor sound: A tutorial
Authors: Gilbert Kenneth E.
Published: March 2016

Understanding the physics and mathematics underlying a computational algorithm such as the Green's function parabolic equation (GFPE) is both useful and worthwhile. To this end, the present article aims to give a more widely accessible derivation of the GFPE algorithm than was given originally by Gilbert and Di [(1993). J. Acoust. Soc. Am. 94, 2343–2352]. The present derivation, which uses mathematics familiar to most engineers and physicists, begins with the separation of variables method, a basic and well-known approach for solving partial differential equations. The method leads naturally to eigenvalue-eigenfunction equations. A step-by-step analysis arrives at relatively simple, analytic expressions for the horizontal and vertical eigenfunctions, which are sinusoids plus a surface wave. The eigenfunctions are superposed in an eigenfunction expansion to yield a one-way propagation solution. The one-way solution is generalized to obtain the GFPE algorithm. In addition, and equally important, the eigenfunctions are used to give concrete meaning to abstract operator solutions for one-way acoustic propagation. By using an eigenfunction expansion of the acoustic field, together with an operator solution, one can obtain the GFPE algorithm very directly and concisely.
Design and implementation of a space domain spherical microphone array with application to source localization and separation
Authors: Bai Mingsian R. , Yao Yueh Hua , Lai Chang-Sheng , Lo Yi-Yang
Published: March 2016

In this paper, four delay-and-sum (DAS) beamformers formulated in the modal domain and the space domain for open and solid spherical apertures are examined through numerical simulations. The resulting beampatterns reveal that the mainlobe of the solid spherical DAS array is only slightly narrower than that of the open array, whereas the sidelobes of the modal domain array are more significant than those of the space domain array due to the discrete approximation of continuous spherical Fourier transformation. To verify the theory experimentally, a three-dimensionally printed spherical array on which 32 micro-electro-mechanical system microphones are mounted is utilized for localization and separation of sound sources. To overcome the basis mismatch problem in signal separation, source localization is first carried out using minimum variance distortionless response beamformer. Next, Tikhonov regularization (TIKR) and compressive sensing (CS) are employed to extract the source signal amplitudes. Simulations and experiments are conducted to validate the proposed spherical array system. Objective perceptual evaluation of speech quality test and a subjective listening test are undertaken in performance evaluation. The experimental results demonstrate better separation quality achieved by the CS approach than by the TIKR approach at the cost of computational complexity.
Survey fraud test sparks battle
Authors: Bohannon John
Published: March 2016

Pew Research Center challenges statistical test.
Scientists to drill into dinosaur-killing blast
Authors: Hand Eric
Published: March 2016

Cores from Chicxulub crater could illuminate how life returned after the cataclysm.
Trial by meltdown
Authors: Hornyak Timothy
Published: March 2016

At Fukushima, robots performed poorly at first but are now critical players in the cleanup.
Electrons go with the flow in exotic material systems
Authors: Zaanen Jan
Published: March 2016

Electronic hydrodynamic flow—making electrons flow like a fluid—has been observed

[Also see Reports by

Bandurin
et al.

,

Crossno
et al.

and

Moll
et al.

]
#IAmAResearchParasite
Authors: McNutt Marcia
Published: March 2016

In the midst of steady progress in policies for data sharing, a recent editorial expressed a contrarian view.
*
The authors described the concern of some scientists about the rise of an underclass of “research parasites” who exploit data sets that are collected and curated by others. Even worse, these parasites might use such data to try to disprove the conclusions posited in the data's original source studies. The editorial raised the points of how anyone not involved in the original study could use the data without misrepresenting it, and the danger of perhaps arriving at erroneous conclusions. The editorial advised instead that data sharing be implemented by involving the authors of the original study as coauthors in follow-up research. The research community immediately took to Twitter under the hashtag #IAmAResearchParasite to voice opposition to the editorial.
Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014
Authors: Demczuk Walter , Martin Irene , Peterson Shelley , Bharat Amrita , Van Domselaar Gary , Graham Morag , Lefebvre Brigitte , Allen Vanessa , Hoang Linda , Tyrrell Greg , Horsman Greg , Wylie John , Haldane David , Archibald Chris , Wong Tom , Unemo Magnus , Mulvey Michael R.
Published: March 2016

The emergence of
Neisseria gonorrhoeae
strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZM
r
) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZM
r
strains. The genomes of 213 AZM
r
and 23 AZM-susceptible
N. gonorrhoeae
isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZM
r
(MICs ≥ 256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (
Escherichia coli
numbering) in all four 23S rRNA alleles. One isolate with high-level AZM
r
collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (
E. coli
numbering) conferred low to moderate levels of AZM
r
(MICs = 2 to 4 and 8 to 32 μg/ml, respectively). Low-level AZM
r
was also associated with
mtrR
promoter mutations, including the −35A deletion and the presence of
Neisseria meningitidis
-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZM
r
strains arise independently and can then rapidly expand clonally in a region through local sexual networks.
The Human Cytomegalovirus
UL116
Gene Encodes an Envelope Glycoprotein Forming a Complex with gH Independently from gL
Authors: Caló Stefano , Cortese Mirko , Ciferri Claudio , Bruno Luca , Gerrein Rachel , Benucci Barbara , Monda Giuseppina , Gentile Michela , Kessler Tobias , Uematsu Yasushi , Maione Domenico , Lilja Anders E. , Carfí Andrea , Merola Marcello
Published: March 2016

Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality in transplant patients and is the leading viral cause of birth defects after congenital infection. HCMV infection relies on the recognition of cell-specific receptors by one of the viral envelope glycoprotein complexes. Either the gH/gL/gO or the gH/gL/UL128/UL130/UL131A (Pentamer) complex has been found to fulfill this role, accounting for HCMV entry into almost all cell types. We have studied the
UL116
gene product, a putative open reading frame identified by
in silico
analysis and predicted to code for a secreted protein. Virus infection experiments in mammalian cells demonstrated that UL116 is expressed late in the HCMV replication cycle and is a heavily glycosylated protein that first localizes to the cellular site of virus assembly and then inserts into the virion envelope. Transient-transfection studies revealed that UL116 is efficiently transported to the plasma membrane when coexpressed with gH and that gL competes with UL116 for gH binding. Further evidence for gH/UL116 complex formation was obtained by coimmunoprecipitation experiments on both transfected and infected cells and biochemical characterization of the purified complex. In summary, our results show that the product of the
UL116
gene is an HCMV envelope glycoprotein that forms a novel gH-based complex alternative to gH/gL. Remarkably, the gH/UL116 complex is the first herpesvirus gH-based gL-less complex.

IMPORTANCE
HCMV infection can cause severe disease in immunocompromised adults and infants infected
in utero
. The dissection of the HCMV entry machinery is important to understand the mechanism of viral infection and to identify new vaccine antigens. The gH/gL/gO and gH/gL/UL128/UL130/UL131 (Pentamer) complexes play a key role in HCMV cell entry and tropism. Both complexes are formed by an invariant gH/gL scaffold on which the other subunits assemble. Here, we show that the
UL116
gene product is expressed in infected cells and forms a heterodimer with gH. The gH/UL116 complex is carried on the infectious virions, although in smaller amounts than gH/gL complexes. No gH/UL116/gL ternary complex formed in transfected cells, suggesting that the gH/UL116 complex is independent from gL. This new gH-based gL-free complex represents a potential target for a protective HCMV vaccine and opens new perspectives on the comprehension of the HCMV cell entry mechanism and tropism.
No economic benefit of early knee reconstruction over optional delayed reconstruction for ACL tears: registry enriched randomised controlled trial data
Authors: Kiadaliri Aliasghar A , Englund Martin , Lohmander L Stefan , Steen Carlsson Katarina , Frobell Richard B
Published: March 2016

Background

To analyse 5-year cost-effectiveness of early versus optional delayed acute anterior cruciate ligament (ACL) reconstruction.

Methods

121 young, active adults with acute ACL injury to a previously uninjured knee were randomised to early ACL reconstruction (n=62, within 10 weeks of injury) or optional delayed ACL reconstruction (n=59; 30 with ACL reconstruction within 6–55 months); all patients received similar structured rehabilitation. Real life data on health care utilisation and sick leave were obtained from regional and national registers. Costs and quality-adjusted life years (QALYs) were discounted at 3%. Full-analysis set (based on study randomisation) and as-treated analysis (according to actual treatment over 5 years) principles were applied.

Results

Mean cost of early ACL reconstruction was €4695 higher than optional delayed ACL reconstruction (p=0.19) and provided an additional 0.13 QALYs (p=0.11). Full-analysis set showed incremental net benefit of early versus optional delayed ACL reconstruction was not statistically significantly different from zero at any level. As-treated analysis showed that costs for rehabilitation alone were €13 650 less than early ACL reconstruction (p<0.001). Results were robust to sensitivity analyses.

Conclusions

In young active adults with acute ACL injury, a strategy of early ACL reconstruction did not provide extra economic value over a strategy of optional delayed ACL reconstruction over a 5-year period. Results from this and previous reports of the KANON-trial imply that early identification of individuals who would benefit from either early ACL reconstruction or rehabilitation alone might reduce resource consumption and decrease risk of unnecessary overtreatment.

Trial registration

ISRCTN84752559.
Development and potential of a clinical resource and educational iPhone and iPad App based on patient testimony
Authors: Levy Andy , Alder Dominic
Published: March 2016

This paper describes the development and production of an educational and reference app designed for the medical and pharmaceutical industries as well as interested members of the public. ‘Clinically Speaking’ consists of edited, impromptu movies of clinical interviews of patients with common and rare conditions archived over two decades. Each is indexed by subject area and disease, identified by short title and thumbnail and accompanied by a description and Wikipedia URL. The app design allows users to scroll down through subject areas such as cardiology and gastroenterology, then across to access several hundred edited cases. For users with Windows, Google or Android rather than iOS devices, a similar experience is delivered through a web-based version. The almost complete market penetration of smart phones and computers allows educational database material to be distributed very economically. An opportunity to partially recoup design and coding costs and cover on-going expenses of upgrades, server charges and annual developer fees is afforded by app store sales. Distributed worldwide via the app store, ‘Clinically Speaking’ constitutes a versatile vehicle for addition of further cases and provides experience of conditions that are infrequently seen in practice. Apps and mobile devices capture the current zeitgeist and constitute potentially powerful new vehicles for delivering reference material and clinical medical education. The development process, described herein, is slow, expensive and complex. The market is saturated and the rationale for adding further apps needs careful consideration.
Lay support for pregnant women with social risk: a randomised controlled trial
Authors: Kenyon Sara , Jolly Kate , Hemming Karla , Hope Lucy , Blissett Jackie , Dann Sophie-Anna , Lilford Richard , MacArthur Christine
Published: March 2016

Objectives

We sought evidence of effectiveness of lay support to improve maternal and child outcomes in disadvantaged families.

Design

Prospective, pragmatic, individually randomised controlled trial.

Setting

3 Maternity Trusts in West Midlands, UK.

Participants

Following routine midwife systematic assessment of social risk factors, 1324 nulliparous women were assigned, using telephone randomisation, to standard maternity care, or addition of referral to a Pregnancy Outreach Worker (POW) service. Those under 16 years and teenagers recruited to the Family Nurse Partnership trial were excluded.

Interventions

POWs were trained to provide individual support and case management for the women including home visiting from randomisation to 6 weeks after birth. Standard maternity care (control) included provision for referring women with social risk factors to specialist midwifery services, available to both arms.

Main outcome measures

Primary outcomes were antenatal visits attended and Edinburgh Postnatal Depression Scale (EPDS) 8–12 weeks postpartum. Prespecified, powered, subgroup comparison was among women with 2 or more social risks. Secondary outcomes included maternal and neonatal birth outcomes; maternal self-efficacy, and mother-to-infant bonding at 8–12 weeks; child development assessment at 6 weeks, breastfeeding at 6 weeks, and immunisation uptake at 4 months, all collected from routine child health systems.

Results

Antenatal attendances were high in the standard care control and did not increase further with addition of the POW intervention (10.1 vs 10.1 (mean difference; MD) −0.00, 95% CI (95% CI −0.37 to 0.37)). In the powered subgroup of women with 2 or more social risk factors, mean EPDS (MD −0.79 (95% CI −1.56 to −0.02) was significantly better, although for all women recruited, no significant differences were seen (MD −0.59 (95% CI −1.24 to 0.06). Mother-to-infant bonding was significantly better in the intervention group for all women (MD −0.30 (95% CI −0.61 to −0.00) p=0.05), and there were no differences in other secondary outcomes.

Conclusions

This trial demonstrates differences in depressive symptomatology with addition of the POW service in the powered subgroup of women with 2 or more social risk factors. Addition to existing evidence indicates benefit from lay interventions in preventing postnatal depression. This finding is important for women and their families given the known effect of maternal depression on longer term childhood outcomes.

Trial registration number

ISRCTN35027323; Results.
Menstrual hygiene management among adolescent girls in India: a systematic review and meta-analysis
Authors: van Eijk Anna Maria , Sivakami M , Thakkar Mamita Bora , Bauman Ashley , Laserson Kayla F , Coates Susanne , Phillips-Howard Penelope A
Published: March 2016

Objectives

To assess the status of menstrual hygiene management (MHM) among adolescent girls in India to determine unmet needs.

Design

Systematic review and meta-analysis. We searched PubMed, The Global Health Database, Google Scholar and references for studies published from 2000 to September 2015 on girls’ MHM.

Setting

India.

Participants

Adolescent girls.

Outcome measures

Information on menarche awareness, type of absorbent used, disposal, hygiene, restrictions and school absenteeism was extracted from eligible materials; a quality score was applied. Meta-analysis was used to estimate pooled prevalence (PP), and meta-regression to examine the effect of setting, region and time.

Results

Data from 138 studies involving 193 subpopulations and 97 070 girls were extracted. In 88 studies, half of the girls reported being informed prior to menarche (PP 48%, 95% CI 43% to 53%, I298.6%). Commercial pad use was more common among urban (PP 67%, 57% to 76%, I299.3%, n=38) than rural girls (PP 32%, 25% to 38%, I298.6%, n=56, p<0.0001), with use increasing over time (p<0.0001). Inappropriate disposal was common (PP 23%, 16% to 31%, I299.0%, n=34). Menstruating girls experienced many restrictions, especially for religious activities (PP 0.77, 0.71 to 0.83, I299.1%, n=67). A quarter (PP 24%, 19% to 30%, I298.5%, n=64) reported missing school during periods. A lower prevalence of absenteeism was associated with higher commercial pad use in univariate (p=0.023) but not in multivariate analysis when adjusted for region (p=0.232, n=53). Approximately a third of girls changed their absorbents in school facilities (PP 37%, 29% to 46%, I297.8%, n=17). Half of the girls’ homes had a toilet (PP 51%, 36% to 67%, I299.4%, n=21). The quality of studies imposed limitations on analyses and the interpretation of results (mean score 3 on a scale of 0–7).

Conclusions

Strengthening of MHM programmes in India is needed. Education on awareness, access to hygienic absorbents and disposal of MHM items need to be addressed.

Trial registration number

CRD42015019197.
Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial
Authors: Lindhardt Morten , Persson Frederik , Currie Gemma , Pontillo Claudia , Beige Joachim , Delles Christian , von der Leyen Heiko , Mischak Harald , Navis Gerjan , Noutsou Marina , Ortiz Alberto , Ruggenenti Piero Luigi , Rychlik Ivan , Spasovski Goce , Rossing Peter
Published: March 2016

Introduction

Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy.

Methods and analysis

Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years.

The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples.

Ethics and dissemination

The study will be conducted under International Conference on Harmonisation – Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy may pave the way for personalised medicine approaches in treatment of diabetes complications.

Trial registration number

NCT02040441; Pre-results.
Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a protocol for a scoping review of the literature and international policies
Authors: Puts Martine T E , Toubasi Samar , Atkinson Esther , Ayala Ana Patricia , Andrew Melissa , Ashe Maureen C , Bergman Howard , Ploeg Jenny , McGilton Katherine S
Published: March 2016

Introduction

With ageing comes increased vulnerability such that older adults’ ability to recover from acute illnesses, fall-related injuries and other stresses related to the physical ageing processes declines. This increased vulnerability, also known as frailty, is common in older adults and associated with increased healthcare service use and adverse health outcomes. Currently, there is no overview of available interventions to prevent or reduce the level of frailty (as defined by study's authors) which will help healthcare providers in community settings caring for older adults. We will address this gap by reviewing interventions and international polices that are designed to prevent or reduce the level of frailty in community-dwelling older adults.

Methods and analysis

We will conduct a scoping review using the updated guidelines of Arksey and O'Malley to systematically search the peer-reviewed journal articles to identify interventions that aimed to prevent or reduce the level of frailty. We will search grey literature for international policies. The 6-stage scoping review model involves: (1) identifying the research question; (2) identifying relevant studies; (3) selecting studies; (4) charting the data; (5) collating, summarising and reporting the results and (6) consulting with key stakeholders.

Ethics and dissemination

Our scoping review will use robust methodology to search for available interventions focused on preventing or reducing the level of frailty in community-dwelling older adults. We will consult with stakeholders to find out whether they find the frailty interventions/policies useful and to identify the barriers and facilitators to their implementation in Canada. We will disseminate our findings to relevant stakeholders at local, national and international levels by presenting at relevant meetings and publishing the findings. Our review will identify gaps in research and provide healthcare providers and policymakers with an overview of interventions that can be implemented to prevent or postpone frailty.
Insuring a veterinary practice: (1) Choosing the right policy
Authors: Harris Judy
Published: March 2016

The right insurance policy can be an important safeguard for a practice, but choosing the right cover can be a daunting task. In this first article in a two‐part series, Judy Harris explains what to look out for in a policy and how to make sure you aren't over‐ or under‐insuring your assets.
Equine distal limb diagnostic anaesthesia: (2) Intrasynovial anaesthesia
Authors: Barker Will
Published: March 2016

Intrasynovial anaesthesia is appropriate when trying to localise lameness further following perineural anaesthesia, or if localising signs implicate the synovial cavity as the source of lameness. A thorough understanding of the complex interactions of intrasynovial local anaesthetic between neighbouring synovial structures, particularly between the distal interphalangeal joint and navicular bursa, is important when performing the procedure, as are skin preparation and personal hygiene when introducing a needle into a synovial cavity. This article, the second in a two‐part series on diagnostic anaesthesia of the distal limb in horses, reviews the basic techniques for intrasynovial distal limb anaesthesia. The first article (Barker 2016) discussed the basic principles of diagnostic anaesthesia and perineural techniques.
Questioning morals
Authors: Brown Richard
Published: March 2016

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.

In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Questioning morals’, was submitted and is discussed by Richard Brown. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘Changing established protocols’, which was published in the February issue of In Practice, appears on page 151.

The series is being coordinated by Steven McCulloch, a practising vet with a PhD in the ethics of veterinary policy. It is hoped it will provide a framework that will help practitioners find solutions when facing similar dilemmas.
Comments on the dilemma in the February issue: ‘Changing established protocols
Authors: McCulloch Steven
Published: March 2016

In the dilemma discussed in the February issue of In Practice, a client had questioned your practice's vaccination protocol for their pet dog and cat. You had attended a CPD event recently in which it was suggested that reduced vaccinations and antibody monitoring might be the most appropriate regime, but this was not common in the local area (IP, February 2016, vol 38, pp 94‐95). Hanne Stabursvik noted that changing vaccination protocols was a big move, and suggested that this should not be done in an ad‐hoc manner. Clients must be considered, and there were some that would not understand why vaccination was being reduced. Strong leadership was needed from professional bodies to support changes such as these, and educational material should be made available. She suggested that, until a profession‐wide change to vaccination protocols had been approved, it might be better to hold off making changes. If clinicians were particularly keen on this change, they could lobby the governing bodies, and even the vaccine manufacturers, to help drive the move.
Laboratory twinning to build capacity for rabies diagnosis
Authors: Fooks Anthony R. , Drew Trevor W. , Tu Changchun
Published: March 2016

In 2009, the UK's OIE Reference Laboratory for rabies, based at the APHA in Weybridge, was awarded a project to twin with the Changchun Veterinary Research Institute in the People's Republic of China to help the institute develop the skills and methods necessary to become an OIE Reference Laboratory itself. Here, Tony Fooks, Trevor Drew and Changchun Tu describe the OIE's twinning project and the success that has since been realised in China