bluuebunny/crossref_metadata_2025 huggingface dataset:
Wages and International Tax Competition
Authors: Krautheim Sebastian , Schmidt‐Eisenlohr Tim
Published: May 2016

We introduce wage bargaining and private information into a model of profit shifting and tax competition between a large and a small country. Shifting profits to the small country not only reduces a firm's tax bill but also creates private information on profitability, altering the wage bargaining in favor of the firm. This additional shifting incentive makes the tax base of the large country more elastic and leads to higher outflows, lower wages, higher firm profits and lower equilibrium tax rates. Tax rates are no longer the only determinant of the direction and extent of profit shifting.
A Frequentist Approach to Computer Model Calibration
Authors: Wong Raymond K. W. , Storlie Curtis B. , Lee Thomas C. M.
Published: May 2016

The paper considers the computer model calibration problem and provides a general frequentist solution. Under the framework proposed, the data model is semiparametric with a non-parametric discrepancy function which accounts for any discrepancy between physical reality and the computer model. In an attempt to solve a fundamentally important (but often ignored) identifiability issue between the computer model parameters and the discrepancy function, the paper proposes a new and identifiable parameterization of the calibration problem. It also develops a two-step procedure for estimating all the relevant quantities under the new parameterization. This estimation procedure is shown to enjoy excellent rates of convergence and can be straightforwardly implemented with existing software. For uncertainty quantification, bootstrapping is adopted to construct confidence regions for the quantities of interest. The practical performance of the methodology is illustrated through simulation examples and an application to a computational fluid dynamics model.
The Impact of Telecommunication Technologies on Competition in Services and Goods Markets: Empirical Evidence
Authors: Jerbashian Vahagn , Kochanova Anna
Published: May 2016

In this paper, we empirically show that a more intensive use and wider adoption of telecommunication technologies significantly increases the level of product market competition in services and goods markets. Our results are consistent with the view that the use of telecommunication technologies can lower the costs of entry and search. These findings are robust to various measures of competition and a wide range of specification checks.
Canine cell line, IPC‐366, as a good model for the study of inflammatory breast cancer
Authors: Caceres S. , Peña L. , Lacerda L. , Illera M. J. , de Andres P. J. , Larson R. A. , Gao H. , Debeb B. G. , Woodward W. A. , Reuben J. M. , Illera J. C.
Published: May 2016

Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor survival in women. Inflammatory mammary cancer (IMC) in dogs is very similar to human IBC and it has been proposed as a good surrogate model for study the human disease. The aim was to determine if IPC‐366 shared characteristics with the IBC cell line SUM149. The comparison was conducted in terms of ability to grow (adherent and nonadherent conditions), stem cell markers expression using flow cytometry, protein production using western blot and tumorigenic capacity. Our results revealed that both are capable of forming long‐term mammospheres with a grape‐like morphology. Adherent and nonadherent cultures exhibited fast growth in vivo. Stem cell markers expressions showed that IPC‐366 and SUM149 in adherent and nonadherent conditions has mesenchymal‐like characteristics, E‐cadherin and N‐cadherin, was higher in adherent than in nonadherent cultures. Therefore, this study determines that both cell lines are similar and IPC‐366 is a good model for the human and canine disease.
Prolongation of survival of dogs with oral malignant melanoma treated byen blocsurgical resection and adjuvantCSPG4‐antigen electrovaccination
Authors: Piras L. A. , Riccardo F. , Iussich S. , Maniscalco L. , Gattino F. , Martano M. , Morello E. , Lorda Mayayo S. , Rolih V. , Garavaglia F. , De Maria R. , Lardone E. , Collivignarelli F. , Mignacca D. , Giacobino D. , Ferrone S. , Cavallo F. , Buracco P.
Published: May 2016

Reported post‐surgery 1‐year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan‐4 (hCSPG4)‐encoded plasmid in 23 dogs with resectedII/III‐stagedCSPG4‐positive oralcMMcompared with 19 dogs with resected onlyII/III‐stagedCSPG4‐positive oralcMM. Vaccination resulted in 6‐, 12‐, 18‐ and 24‐month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78–1694, 8 of 23 dogs alive] and 6‐, 12‐, 18‐ and 24‐month disease‐free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI477 days, range 50–1694). Non‐vaccinated dogs showed 6‐, 12‐, 18‐ and 24‐month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST200 days, range 75–1507, 1 of 19 dogs alive) and 6‐, 12‐, 18‐ and 24‐monthDFIrate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI180 days, range 38–1250). Overall survival andDFIof vaccinated dogs was longer in those <20 kg. In vaccinated and non‐vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively.
Retrospective evaluation of acute liver failure in dogs (1995–2012): 49 cases
Authors: Lester Carrie , Cooper Johanna , Peters Rachel M. , Webster Cynthia R. L.
Published: May 2016

Objective

To characterize the clinical presentation and outcome of dogs with acute liver failure (ALF).

Design

Retrospective case series from January 1995 to December 2012.

Setting

University teaching hospital.

Animals

Forty‐nine dogs were diagnosed with ALF defined as the acute onset of clinical signs accompanied by serum hyperbilirubinemia and coagulopathy (prothrombin time >1.5 times the upper limit of the reference interval) with or without signs of hepatic encephalopathy.

Methods

Medical records were retrospectively analyzed for clinical presentation, history, physical examination findings, clinicopathologic data, diagnostic imaging findings, hepatic histopathology, treatment, and outcome.

Main Results

Presenting signs included anorexia (28/49, 57%), vomiting (25/49, 51%), neurologic abnormalities (17/49, 35%), and polydipsia/polyuria (10/49, 20%). Neurologic impairment compatible with hepatic encephalopathy occurred at some point during hospitalization in 28/49 (57%) of dogs. Common clinicopathologic abnormalities on presentation other than hyperbilirubinemia and increased serum liver enzyme activity included thrombocytopenia (25/49, 51%), hypoalbuminemia (23/49, 46%), leukocytosis (17/49, 34%), anemia (14/49, 29%), hypokalemia (13/49, 27%), and hypoglycemia (10/49, 20%). The causes of ALF included neoplasia (13/49, 27%), presumptive leptosporosis (4/49, 8%), and ischemia (1/49, 2%). The remaining cases were idiopathic although 15 of these dogs had exposure to possible hepatotoxins. Common lesions in the 35/49 (71%) dogs that had hepatic histopathology were necrosis (19/39, 48%), lipidosis (16/39, 41%), vacuolar change (7/49, 14%), and inflammation (4/49, 8%). Complications included ascites (20/49, 41%), bleeding tendencies (14/49, 29%), pancreatitis (12/49, 24%), and acute tubular necrosis (11/49, 22%). Seven (14%) dogs survived to discharge. Survivors had higher alanine aminotransferase activity, and were more likely to maintain normal albumin concentrations and not develop clinical bleeding or ascites during hospitalization.

Conclusions

Canine ALF is associated with multiple etiologies and a high mortality rate. Strategies to increase survival are urgently required.
The transcription factor NeuroD2 coordinates synaptic innervation and cell intrinsic properties to control excitability of cortical pyramidal neurons
Authors: Chen Fading , Moran Jacqueline T. , Zhang Yihui , Ates Kristin M. , Yu Diankun , Schrader Laura A. , Das Partha M. , Jones Frank E. , Hall Benjamin J.
Published: May 2016

Key points

Synaptic excitation and inhibition must be properly balanced in individual neurons and neuronal networks to allow proper brain function.

Disrupting this balance may lead to autism spectral disorders and epilepsy.

We show the basic helix–loop–helix transcription factor NeuroD2 promotes inhibitory synaptic drive but also decreases cell‐intrinsic neuronal excitability of cortical pyramidal neurons both in vitro and in vivo.

We identify two genes potentially downstream of NeuroD2‐mediated transcription that regulate these parameters: gastrin‐releasing peptide and the small conductance, calcium‐activated potassium channel, SK2.

Our results reveal an important function for NeuroD2 in balancing synaptic neurotransmission and intrinsic excitability.

Our results offer insight into how synaptic innervation and intrinsic excitability are coordinated during cortical development.

Synaptic excitation and inhibition must be properly balanced in individual neurons and neuronal networks for proper brain function. Disruption of this balance during development may lead to autism spectral disorders and epilepsy. Synaptic excitation is counterbalanced by synaptic inhibition but also by attenuation of cell‐intrinsic neuronal excitability. To maintain proper excitation levels during development, neurons must sense activity over time and regulate the expression of genes that control these parameters. While this is a critical process, little is known about the transcription factors involved in coordinating gene expression to control excitatory/inhibitory synaptic balance. We show here that the basic helix–loop–helix transcription factor NeuroD2 promotes inhibitory synaptic drive but also decreases cell‐intrinsic neuronal excitability of cortical pyramidal neurons both in vitro and in vivo as shown by ex vivo analysis of a NeuroD2 knockout mouse. Using microarray analysis and comparing wild‐type and NeuroD2 knockout cortical networks, we identified two potential gene targets of NeuroD2 that contribute to these processes: gastrin‐releasing peptide (GRP) and the small conductance, calcium‐activated potassium channel, SK2. We found that the GRP receptor antagonist RC‐3059 and the SK2 specific blocker apamin partially reversed the effects of increased NeuroD2 expression on inhibitory synaptic drive and action potential repolarization, respectively. Our results reveal an important function for NeuroD2 in balancing synaptic neurotransmission and intrinsic excitability and offer insight into how these processes are coordinated during cortical development.
Heterogeneous firing rate response of mouse layer V pyramidal neurons in the fluctuation‐driven regime
Authors: Zerlaut Y. , Teleńczuk B. , Deleuze C. , Bal T. , Ouanounou G. , Destexhe A.
Published: May 2016

Key points

We recreated in vitro the fluctuation‐driven regime observed at the soma during asynchronous network activity in vivo and we studied the firing rate response as a function of the properties of the membrane potential fluctuations.

We provide a simple analytical template that captures the firing response of both pyramidal neurons and various theoretical models.

We found a strong heterogeneity in the firing rate response of layer V pyramidal neurons: in particular, individual neurons differ not only in their mean excitability level, but also in their sensitivity to fluctuations.

Theoretical modelling suggest that this observed heterogeneity might arise from various expression levels of the following biophysical properties: sodium inactivation, density of sodium channels and spike frequency adaptation.

Characterizing the input–output properties of neocortical neurons is of crucial importance for understanding the properties emerging at the network level. In the regime of low‐rate irregular firing (such as in the awake state), determining those properties for neocortical cells remains, however, both experimentally and theoretically challenging. Here, we studied this problem using a combination of theoretical modelling and in vitro experiments. We first identified, theoretically, three somatic variables that describe the dynamical state at the soma in this fluctuation‐driven regime: the mean, standard deviation and time constant of the membrane potential fluctuations. Next, we characterized the firing rate response of individual layer V pyramidal cells in this three‐dimensional space by means of perforated‐patch recordings and dynamic clamp in the visual cortex of juvenile mice in vitro. We found that individual neurons strongly differ not only in terms of their excitability, but also, and unexpectedly, in their sensitivities to fluctuations. Finally, using theoretical modelling, we attempted to reproduce these results. The model predicts that heterogeneous levels of biophysical properties such as sodium inactivation, sharpness of sodium activation and spike frequency adaptation account for the observed diversity of firing rate responses. Because the firing rate response will determine population rate dynamics during asynchronous neocortical activity, our results show that cortical populations are functionally strongly inhomogeneous in young mouse visual cortex, which should have important consequences on the strategies of cortical computation at early stages of sensory processing.
Investigations on the Influence of Flow Migration on Flow and Heat Transfer in Oblique Fin Microchannel Array
Authors: Mou Nasi , Jiun Lee Yong , Seng Lee Poh , Singh Pawan K. , Khan Saif A.
Published: May 2016

In order to scrutinize the coolant mass distribution and its effect to the heat transfer in oblique fin microchannel array, extensive numerical studies are performed on planar oblique fin configuration. Full-domain simulations using common-flow down (CFD) approach are employed to provide better insights into the flow distribution, flow stability, and heat transfer performance at a global level. The flow field and temperature profile analysis shows that nonuniform coolant distribution and coolant migration occur in the oblique fin microchannel, and the heat transfer performance for both edges of the heat sink is affected due to changing secondary flow rate. However, the flow migration does not affect the local coolant velocity and temperature profiles significantly in the middle region (0.2 < Z′ < 0.8). Meanwhile, it is also found that Reynolds number affects the coolant migration, the stability of the fluid flow, and heat transfer performance significantly. Higher Reynolds number increases the percentage of secondary flow rate and, hence, enhances the heat transfer for fin surfaces in secondary channels.
Recent applications of hard x-ray photoelectron spectroscopy
Authors: Weiland Conan , Rumaiz Abdul K. , Pianetta Piero , Woicik Joseph C.
Published: May 2016

Recent applications of hard x-ray photoelectron spectroscopy (HAXPES) demonstrate its many capabilities in addition to several of its limitations. Examples are given, including measurement of buried interfaces and materials under in situ or in operando conditions, as well as measurements under x-ray standing-wave and resonant excitation. Physical considerations that differentiate HAXPES from photoemission measurements utilizing soft x-ray and ultraviolet photon sources are also presented.
Clinical Trial of an Oral Live Shigella sonnei Vaccine Candidate, WRSS1, in Thai Adults
Authors: Pitisuttithum Punnee , Islam Dilara , Chamnanchanunt Supat , Ruamsap Nattaya , Khantapura Patchariya , Kaewkungwal Jaranit , Kittitrakul Chatporn , Luvira Viravarn , Dhitavat Jittima , Venkatesan Malabi M. , Mason Carl J. , Bodhidatta Ladaporn
Published: May 2016

Live attenuatedShigella sonneivaccine candidate WRSS1, previously tested in U.S. and Israeli volunteers, was evaluated in a population of adult Thai volunteers in which the organism is endemic. In a randomized placebo-controlled, double-blind design, inpatient participants received a single oral dose of 1.6 × 104CFU of WRSS1. The vaccine was generally well tolerated, with equal numbers of vaccinees and placebo controls showing mild symptoms. Only 3 of 13 vaccinees (23%) had culture-positive stools, while a total of 9 vaccinees were positive by PCR. Lack of vaccine shedding in volunteers correlated with lack of clinical symptoms and immune responses, just as the duration of fecal shedding correlated directly with stronger immune responses. Two months following immunization, 10 vaccinees and 10 newly recruited naive controls received a challenge dose of 1,670 CFU of virulentS. sonneistrain 53G. This dose had previously demonstrated a 75% attack rate for dysentery in Thai volunteers. However, in this study the attack rate for dysentery in naive controls after challenge was 20%. Based on clinical record summaries, 3 vaccinees and 5 naive controls experienced clinically relevant illness (diarrhea/dysentery/fever/shigellosis), and a 40% vaccine efficacy was calculated. When these data are compared to those for the performance of this vaccine candidate in more naive populations, it is clear that a single oral dose of WRSS1 at 104CFU failed to achieve its full potential in a population in which the organism is endemic. Higher doses and/or repeated immunizations may contribute to improved vaccine shedding and consequent elevation of protective immune responses in a population in which the organism is endemic. (The study has been registered at ClinicalTrials.gov under registration no. NCT01080716.)
Resistance Mechanisms, Epidemiology, and Approaches to Screening for Vancomycin-Resistant Enterococcus in the Health Care Setting
Authors: Faron Matthew L. , Ledeboer Nathan A. , Buchan Blake W.
Published: May 2016

Infections attributable to vancomycin-resistant
Enterococcus
(VRE) strains have become increasingly prevalent over the past decade. Prompt identification of colonized patients combined with effective multifaceted infection control practices can reduce the transmission of VRE and aid in the prevention of hospital-acquired infections (HAIs). Increasingly, the clinical microbiology laboratory is being asked to support infection control efforts through the early identification of potential patient or environmental reservoirs. This review discusses the factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens.
Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Fails To Identify Nontuberculous Mycobacteria from Primary Cultures of Respiratory Samples
Authors: van Eck Kim , Faro Dirk , Wattenberg Melanie , de Jong Arjan , Kuipers Saskia , van Ingen Jakko
Published: May 2016

We have assessed matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) identification (Bruker) of nontuberculous mycobacteria from newly positive liquid cultures of respiratory samples. Twelve (22%) of 54 isolates were identified directly from liquid medium. After subculture and with manual laser operation, this rose to 49/54 isolates (91%). MALDI-TOF MS is less promising than previously suggested.
Assessing Immunity to Rubella Virus: a Plea for Standardization of IgG (Immuno)assays
Authors: Bouthry Elise , Furione Milena , Huzly Daniela , Ogee-Nwankwo Adaeze , Hao LiJuan , Adebayo Adebola , Icenogle Joseph , Sarasini Antonella , Revello Maria Grazia , Grangeot-Keros Liliane , Vauloup-Fellous Christelle
Published: May 2016

Immunity to rubella virus (RV) is commonly determined by measuring specific immunoglobulin G (RV IgG). However, RV IgG results and their interpretation may vary, depending on the immunoassay, even though most commercial immunoassays (CIAs) have been calibrated against an international standard and results are reported in international units per milliliter. A panel of 322 sera collected from pregnant women that tested negative or equivocal for RV IgG in a prior test (routine screening) was selected. This panel was tested with two reference tests, immunoblotting (IB) and neutralization (Nt), and with 8 CIAs widely used in Europe. IB and Nt gave concordant results on 267/322 (82.9%) sera. Of these, 85 (26.4%) sera were negative and 182 (56.5%) sera were positive for both tests. All 85 IB/Nt-negative samples were classified as negative with all CIAs. Of the 182 IB/Nt-positive samples, 25.3 to 61.5% were classified as equivocal and 6 to 64.8% were classified as positive with the CIAs. Wide variations in titers in international units per milliliter were observed. In our series, more than half of the women considered susceptible to RV based on CIA results tested positive for RV antibodies by IB/Nt. Our data suggest that (i) sensitivity of CIAs could be increased by considering equivocal results as positive and (ii) the definition of immunity to RV as the 10-IU/ml usual cutoff as well as the use of quantitative results for clinical decisions may warrant reconsideration. A better standardization of CIAs for RV IgG determination is needed.
Detection of Aspergillus fumigatus in Blood Samples from Critically Ill Patients in Intensive Care Units by Use of the SeptiFast Assay
Authors: Steinmann Joerg , Buer Jan , Rath Peter-Michael
Published: May 2016

We retrospectively analyzed the performance and relevance of the SeptiFast assay in detecting
Aspergillus fumigatus
DNA in whole blood samples from 38 critically ill intensive care unit (ICU) patients with probable or proven invasive aspergillosis (IA) and 100 ICU patients without IA. The assay exhibited 66% sensitivity, 98% specificity, a 93% positive predictive value, and an 88% negative predictive value.
A. fumigatus
DNAemia was associated with poor outcome.
Functional Regulation of an Autographa californica Nucleopolyhedrovirus-Encoded MicroRNA, AcMNPV-miR-1, in Baculovirus Replication
Authors: Zhu Mengxiao , Wang Jinwen , Deng Riqiang , Wang Xunzhang
Published: May 2016

An Autographa californica nucleopolyhedrovirus-encoded microRNA (miRNA), AcMNPV-miR-1, downregulates the
ac94
gene, reducing the production of infectious budded virions and accelerating the formation of occlusion-derived virions. In the current study, four viruses that constitutively overexpress AcMNPV-miR-1 were constructed to further explore the function of the miRNA. In addition to the
ac94
gene, two new viral gene targets (
ac18
and
ac95
) of AcMNPV-miR-1 were identified, and the possible interacting proteins were verified and tested. In the context of AcMNPV-miR-1 overexpression,
ac18
was slightly upregulated, and
ac95
was downregulated. Several interacting proteins were identified, and a functional pathway for AcMNPV-miR-1 was deduced. AcMNPV-miR-1 overexpression decreased budded virus infectivity, reduced viral DNA replication, accelerated polyhedron formation, and promoted viral infection efficiency in
Trichoplusia ni
larvae, suggesting that AcMNPV-miR-1 restrains virus infection of cells but facilitates virus infection of larvae.

IMPORTANCE
Recently, microRNAs (miRNAs) have been widely reported as moderators or regulators of mammalian cellular processes, especially disease-related pathways in humans. However, the roles played by miRNAs encoded by baculoviruses, which infect numerous beneficial insects and agricultural pests, have rarely been described. To explore the actions of virus-encoded miRNAs, we investigated an miRNA encoded by Autographa californica nucleopolyhedrovirus (AcMNPV-miR-1). We previously identified this miRNA through the exogenous addition of AcMNPV-miR-1 mimics. In the current study, we constitutively overexpressed AcMNPV-miR-1 and analyzed the resultant effects to more comprehensively assess what is indeed the function of this miRNA during viral infection. In addition, we widely explored the target genes for the miRNA in the viral and host genomes and proposed a possible functional network for AcMNPV-miR-1, which provides a better general understanding of virus-encoded miRNAs. In brief, our study implied that AcMNPV-miR-1 constrains viral replication and cellular infection but enhances larval infection.
A Norwegian prospective study of preterm mother–infant interactions at 6 and 18 months and the impact of maternal mental health problems, pregnancy and birth complications
Authors: Misund Aud R , Bråten Stein , Nerdrum Per , Pripp Are Hugo , Diseth Trond H
Published: May 2016

Objective

Pregnancy, birth and health complications, maternal mental health problems following preterm birth and their possible impact on early mother–infant interaction at 6 and 18 months corrected age (CA) were explored. Predictors of mother–infant interaction at 18 months CA were identified.

Design and methods

This prospective longitudinal and observational study included 33 preterm mother–infant (<33 gestational age (GA)) interactions at 6 and 18 months CA from a socioeconomic low-risk, middle-class sample. The Parent–Child Early Relational Assessment (PCERA) scale was used to assess the mother–infant interaction.

Results

‘Bleeding in pregnancy’ predicted lower quality in preterm mother–infant interaction in 6 PCERA scales, while high ‘maternal trait anxiety’ predicted higher interactional quality in 2 PCERA scales and ‘family size’ predicted lower interactional quality in 1 PCERA scale at 18 months CA. Mothers with symptoms of post-traumatic stress reactions, general psychological distress and anxiety at 2 weeks postpartum (PP) showed significantly better outcome than mothers without symptoms in 6 PCERA subscales at 6 months CA and 2 PCERA subscales at 18 months CA.

Conclusions

Our study detected a correspondence between early pregnancy complications and lower quality of preterm mother–infant interaction, and an association between high levels of maternal mental health problems and better quality in preterm mother–infant interaction.
Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis
Authors: Li Tong , Ke Wenbo , Sun Ping , Chen Xiang , Belgaumkar Ajay , Huang Yuanjian , Xian Wenjing , Li Jinjin , Zheng Qichang
Published: May 2016

Objective

To assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension.

Design

A systematic review and meta-analysis.

Data sources

We searched PubMed, Cochrane library databases, EMBASE and the Science Citation Index Expanded through December 2015. Only randomised controlled trials (RCTs) were included.

Outcome measure

We calculated clinical outcomes (all-cause mortality, bleeding-related mortality, upper gastrointestinal bleeding) as well as haemodynamic outcomes (hepatic venous pressure (HVPG) reduction, haemodynamic response rate, post-treatment arterial blood pressure (mean arterial pressure; MAP) and adverse events).

Results

12 RCTs were included. In 7 trials that looked at haemodynamic outcomes compared carvedilol versus propranolol, showing that carvedilol was associated with a greater reduction (%) of HVPG within 6 months (mean difference −8.49, 95% CI −12.36 to −4.63) without a greater reduction in MAP than propranolol. In 3 trials investigating differences in clinical outcomes between carvedilol versus endoscopic variceal band ligation (EVL), no significant differences in mortality or variceal bleeding were demonstrated. 1 trial compared clinical outcomes between carvedilol versus nadolol plus isosorbide-5-mononitrate (ISMN), and showed that no significant difference in mortality or bleeding had been found. 1 trial comparing carvedilol versus nebivolol showed a greater reduction in HVPG after 14 days follow-up in the carvedilol group.

Conclusions

Carvedilol may be more effective in decreasing HVPG than propranolol or nebivolol and it may be as effective as EVL or nadolol plus ISMN in preventing variceal bleeding. However, the overall quality of evidence is low. Further large-scale randomised studies are required before we can make firm conclusions.

Trial registration number

CRD42015020542.
The emerging world of animal hospice: (1) Introduction
Authors: Cooney Kathleen A.
Published: May 2016

Animal hospice is an emerging field that aims to maintain an animal's wellbeing and dignity at the end of its life. Here, Kathleen Cooney describes the hospice philosophy of care and ways to support owners when they are are making decisions before, around and after their pet's death. In a second article, to be published in a forthcoming issue of In Practice, she will discuss possible animal hospice business strategies.
Disposing of veterinary practice leases
Authors: Long Richard
Published: May 2016

There are a variety of situations where a vet may wish to leave the property and dispose of the practice lease before the end of the lease term. Richard Long discusses ways of disposing a lease and the importance of making a circumstantial decision to ensure the transaction proceeds smoothly and on time.
Improving stock assessments through data prioritization
Authors: Siegfried Kate I. , Williams Erik H. , Shertzer Kyle W. , Coggins Lewis G.
Published: May 2016

The need for “better data” is a common response of stakeholders and managers when confronted with the uncertainty of advice resulting from quantitative stock assessments. Most contemporary stock assessments are based on an integrated analysis of multiple data types, each with their associated cost to collect. Data collection resources are inevitably limited; therefore, it is important to quantify the relative value of increased sampling for alternative data types in terms of improving stock assessments. We approached this universal problem using a simulation study of a hypothetical, amalgam species developed from eight separate stock assessments conducted for species found in southeastern US Atlantic waters. We simulated a population and a stock assessment from the amalgam species and then individually improved alternative data types (indices, age compositions, landings, and discards) by increasing either precision or sample size. We also simulated the effects of increased sampling for alternative groupings of data that might be collected in concert (e.g., commercial, recreational, or survey). Our results show that for the snapper–grouper complex we modeled, age composition data have the largest effect on the accuracy of assessments, with commercial age compositions being the most influential. This is due in part to the relative paucity of age composition data for many southeast US marine stocks, so that modest increases in collection efforts have relatively high benefits for age-based assessment models currently in use for the region. Though this study used data from a particular region of the US, our investigative framework is broadly applicable for quantitatively evaluating the benefits of improved data collection in terms of the precision of stock assessments in any region.
Bifurcation Sequences in the Symmetric 1:1 Hamiltonian Resonance
Authors: Marchesiello Antonella , Pucacco Giuseppe
Published: May 2016

We present a general review of the bifurcation sequences of periodic orbits in general position of a family of resonant Hamiltonian normal forms with nearly equal unperturbed frequencies, invariant under [Formula: see text] symmetry. The rich structure of these classical systems is investigated with geometric methods and the relation with the singularity theory approach is also highlighted. The geometric approach is the most straightforward way to obtain a general picture of the phase-space dynamics of the family as is defined by a complete subset in the space of control parameters complying with the symmetry constraint. It is shown how to find an energy-momentum map describing the phase-space structure of each member of the family, a catastrophe map that captures its global features and formal expressions for action-angle variables. Several examples, mainly taken from astrodynamics, are used as applications.
Steady-State Bifurcation for a Biological Depletion Model
Authors: Wang Yan’e , Wu Jianhua , Jia Yunfeng
Published: May 2016

A two-species biological depletion model in a bounded domain is investigated in which one species is a substrate and the other is an activator. Firstly, under the no-flux boundary condition, the asymptotic stability of constant steady-states is discussed. Secondly, by viewing the feed rate of the substrate as a parameter, the steady-state bifurcations from constant steady-states are analyzed both in one-dimensional kernel case and in two-dimensional kernel case. Finally, numerical simulations are presented to illustrate our theoretical results. The main tools adopted here include the stability theory, the bifurcation theory, the techniques of space decomposition and the implicit function theorem.
K out of N Secret Sharing Scheme for Multiple Color Images with Steganography and Authentication
Authors: Fathimal P. Mohamed , Rani P. Arockia Jansi
Published: May 2016

With our lives trundling toward a fully-digital ecosystem in break-neck speed, today’s encryption and cryptography are facing the challenge of ensuring security and future-readiness of our transactions. When such transactions involve multiple hands, transmission of such data in discrete and recoverable parts (secret shares) guarantees confidentiality. This paper’s objective is to present a foolproof way of multiple secret sharing, eliminating issues such as half-toning and degradation of visual quality of the recovered images. This [Formula: see text] out of [Formula: see text] steganography and authenticated image sharing (SAIS) scheme for multiple color images generates [Formula: see text] relevant shares with the ability to reconstruct the secret images using [Formula: see text] shares and facility to find out any move for appropriation of share cover images. The key aspects of this proposed scheme is to use simple Boolean and arithmetic operations with reduction of computational complexity from [Formula: see text] to [Formula: see text] and to share multiple images without any pixel expansion.
Almost Optimal Local Graph Clustering Using Evolving Sets
Authors: Andersen Reid , Gharan Shayan Oveis , Peres Yuval , Trevisan Luca
Published: May 2016

Spectral partitioning is a simple, nearly linear time algorithm to find sparse cuts, and the Cheeger inequalities provide a worst-case guarantee for the quality of the approximation found by the algorithm. A
local graph partitioning algorithm
finds a set of vertices with small conductance (i.e., a sparse cut) by adaptively exploring part of a large graph
G
, starting from a specified vertex. For the algorithm to be local, its complexity must be bounded in terms of the size of the set that it outputs, with at most a weak dependence on the number
n
of vertices in
G
. Previous local partitioning algorithms find sparse cuts using random walks and personalized PageRank [Spielman and Teng 2013; Andersen et al. 2006].

In this article, we introduce a simple randomized local partitioning algorithm that finds a sparse cut by simulating the
volume-biased evolving set process
, which is a Markov chain on sets of vertices. We prove that for any ϵ > 0, and any set of vertices
A
that has conductance at most φ, for at least half of the starting vertices in
A
our algorithm will output (with constant probability) a set of conductance
O
(√φ /ϵ). We prove that for a given run of the algorithm, the expected ratio between its computational complexity and the volume of the set that it outputs is vol(
A
)
ϵ
φ
-1/2
polylog(
n
), where vol(
A
) = Σ

v
∈
A

d
(
v
) is the volume of the set
A
. This gives an algorithm with the same guarantee (up to a constant factor) as the Cheeger's inequality that runs in time slightly superlinear in the size of the output. This is the first sublinear (in the size of the input) time algorithm with almost the same guarantee as the Cheeger's inequality. In comparison, the best previous local partitioning algorithm, by Andersen et al. [2006], has a worse approximation guarantee of
O
(√φ log
n
) and a larger ratio of φ
-1
polylog(
n
) between the complexity and output volume.

As a by-product of our results, we prove a bicriteria approximation algorithm for the expansion profile of any graph. For 0 <
k
≤ vol(
V
)/2, let φ(
k
) : min

S
: vol(
S
) ≤
k

φ(
S
). There is a polynomial time algorithm that, for any
k
, ϵ > 0, finds a set
S
of volume vol(
S
) ≤
O
(
k
1 + ϵ
) and expansion φ(
S
)≤
O
(√φ (
k
)/ϵ). As a new technical tool, we show that for any set
S
of vertices of a graph, a lazy
t
-step random walk started from a randomly chosen vertex of
S
will remain entirely inside
S
with probability at least (1 - φ(
S
)/2)

t

. This itself provides a new lower bound to the uniform mixing time of any finite state reversible Markov chain.
Radical S-Adenosylmethionine Enzymes in Human Health and Disease
Authors: Landgraf Bradley J. , McCarthy Erin L. , Booker Squire J.
Published: May 2016

Radical S-adenosylmethionine (SAM) enzymes catalyze an astonishing array of complex and chemically challenging reactions across all domains of life. Of approximately 114,000 of these enzymes, 8 are known to be present in humans: MOCS1, molybdenum cofactor biosynthesis; LIAS, lipoic acid biosynthesis; CDK5RAP1, 2-methylthio-N6-isopentenyladenosine biosynthesis; CDKAL1, methylthio-N6-threonylcarbamoyladenosine biosynthesis; TYW1, wybutosine biosynthesis; ELP3, 5-methoxycarbonylmethyl uridine; and RSAD1 and viperin, both of unknown function. Aberrations in the genes encoding these proteins result in a variety of diseases. In this review, we summarize the biochemical characterization of these 8 radical S-adenosylmethionine enzymes and, in the context of human health, describe the deleterious effects that result from such genetic mutations.
Dietary Protein, Metabolism, and Aging
Authors: Soultoukis George A. , Partridge Linda
Published: May 2016

Dietary restriction (DR), a moderate reduction in food intake, improves health during aging and extends life span across multiple species. Specific nutrients, rather than overall calories, mediate the effects of DR, with protein and specific amino acids (AAs) playing a key role. Modulations of single dietary AAs affect traits including growth, reproduction, physiology, health, and longevity in animals. Epidemiological data in humans also link the quality and quantity of dietary proteins to long-term health. Intricate nutrient-sensing pathways fine tune the metabolic responses to dietary AAs in a highly conserved manner. In turn, these metabolic responses can affect the onset of insulin resistance, obesity, neurodegenerative disease, and other age-related diseases. In this review we discuss how AA requirements are shaped and how ingested AAs regulate a spectrum of homeostatic processes. Finally, we highlight the resulting opportunity to develop nutritional strategies to improve human health during aging.
Ice-Binding Proteins and Their Function
Authors: Bar Dolev Maya , Braslavsky Ido , Davies Peter L.
Published: May 2016

Ice-binding proteins (IBPs) are a diverse class of proteins that assist organism survival in the presence of ice in cold climates. They have different origins in many organisms, including bacteria, fungi, algae, diatoms, plants, insects, and fish. This review covers the gamut of IBP structures and functions and the common features they use to bind ice. We discuss mechanisms by which IBPs adsorb to ice and interfere with its growth, evidence for their irreversible association with ice, and methods for enhancing the activity of IBPs. The applications of IBPs in the food industry, in cryopreservation, and in other technologies are vast, and we chart out some possibilities.
Self-Organization and Forces in the Mitotic Spindle
Authors: Pavin Nenad , Tolić Iva M.
Published: May 2016

At the onset of division, the cell forms a spindle, a precise self-constructed micromachine composed of microtubules and the associated proteins, which divides the chromosomes between the two nascent daughter cells. The spindle arises from self-organization of microtubules and chromosomes, whose different types of motion help them explore the space and eventually approach and interact with each other. Once the interactions between the chromosomes and the microtubules have been established, the chromosomes are moved to the equatorial plane of the spindle and ultimately toward the opposite spindle poles. These transport processes rely on directed forces that are precisely regulated in space and time. In this review, we discuss how microtubule dynamics and their rotational movement drive spindle self-organization, as well as how the forces acting in the spindle are generated, balanced, and regulated.
Engineering Delivery Vehicles for Genome Editing
Authors: Nelson Christopher E. , Gersbach Charles A.
Published: May 2016

The field of genome engineering has created new possibilities for gene therapy, including improved animal models of disease, engineered cell therapies, and in vivo gene repair. The most significant challenge for the clinical translation of genome engineering is the development of safe and effective delivery vehicles. A large body of work has applied genome engineering to genetic modification in vitro, and clinical trials have begun using cells modified by genome editing. Now, promising preclinical work is beginning to apply these tools in vivo. This article summarizes the development of genome engineering platforms, including meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas9, and their flexibility for precise genetic modifications. The prospects for the development of safe and effective viral and nonviral delivery vehicles for genome editing are reviewed, and promising advances in particular therapeutic applications are discussed.
Lithification Mechanisms for Planetary Regoliths: The Glue that Binds
Authors: Spray John G.
Published: May 2016

It is understood how rocks are made on Earth. However, on the Moon, Mercury, and, to a lesser extent, Mars and Venus, there are distinct rock-forming processes that we do not fully comprehend. The surfaces and crusts of the inner planetary bodies may retain a history of disruption by hypervelocity impact resulting in the generation of disaggregated materials to several kilometers depth. The uppermost component of this is called regolith (typically <20 m thick on the Moon), which is part of a more extensive megaregolith that is up to tens of kilometers thick, and which in places may pervade the entire crust of a planetary body. It is from these pulverized materials that new rocks are reaggregated to form so-called breccias. This work reviews regolith and megaregolith structure for the inner planetary bodies and investigates how extraterrestrial breccias are produced. Three principal formation mechanisms are explored: thermal sintering, shock sintering, and the dynamic interaction of impact-generated melt with fragmental material.
Redox Effects on Organic Matter Storage in Coastal Sediments During the Holocene: A Biomarker/Proxy Perspective
Authors: Bianchi Thomas S. , Schreiner Kathryn M. , Smith Richard W. , Burdige David J. , Woodard Stella , Conley Daniel J.
Published: May 2016

Coastal margins play a significant role in the burial of organic matter (OM) on Earth. These margins vary considerably with respect to their efficiency in OM burial and to the amounts and periodicity of their OM delivery, depending in large part on whether they are passive or active margins. In the context of global warming, these coastal regions are expected to experience higher water temperatures, changes in riverine inputs of OM, and sea level rise. Low-oxygen conditions continue to expand around the globe in estuarine regions (i.e., hypoxic zones) and shelf regions (i.e., oxygen minimum zones), which will impact the amounts and sources of OM stored in these regions. In this review, we explore how these changes are impacting the storage of OM and the preservation of sedimentary biomarkers, used as proxies to reconstruct environmental change, in coastal margins.
The Great Adventure of an American Human Geneticist
Authors: Motulsky Arno G. , King Mary-Claire
Published: May 2016

It is my great pleasure to have been asked by the Editorial Committee of the Annual Review of Genomics and Human Genetics to write a short autobiography of my life in genetics over the past 70 years. It has been a great adventure. I came both to America and to human genetics by a circuitous and ultimately very fortunate route. I hope the next generation of geneticists will enjoy reading about it.
Next-Generation Environmental Regulation: Law, Regulation, and Governance
Authors: Gunningham Neil , Holley Cameron
Published: May 2016

This article analyzes more than four decades of environmental law, regulation, and governance in various Anglo-Saxon and global jurisdictions. It shows how, after the heydays of law and command and control and the swing to economic instruments, voluntarism, and light-handed initiatives, new phases evolved—their most important manifestations being pluralistic regulation, new technologies, compliance, and new governance. It shows how each of the frameworks examined proposes its own solutions and has something valuable to offer, as well as its own limitations. The article concludes by discussing a fundamental challenge confronting the field, namely, how to orchestrate the many possible approaches and relationships available on the legal, regulatory, and governance spectrum.
The Emergence of a Circuit Model for Addiction
Authors: Lüscher Christian
Published: May 2016

Addiction is a disease of altered behavior. Addicts use drugs compulsively and will continue to do so despite negative consequences. Even after prolonged periods of abstinence, addicts are at risk of relapse, particularly when cues evoke memories that are associated with drug use. Rodent models mimic many of the core components of addiction, from the initial drug reinforcement to cue-associated relapse and continued drug intake despite negative consequences. Rodent models have also enabled unprecedented mechanistic insight into addiction, revealing plasticity of glutamatergic synaptic transmission evoked by the strong activation of mesolimbic dopamine—a defining feature of all addictive drugs—as a neural substrate for these drug-adaptive behaviors. Cell type–specific optogenetic manipulations have allowed both identification of the relevant circuits and design of protocols to reverse drug-evoked plasticity and to establish links of causality with drug-adaptive behaviors. The emergence of a circuit model for addiction will open the door for novel therapies, such as deep brain stimulation.
Reward and Aversion
Authors: Hu Hailan
Published: May 2016

To benefit from opportunities and cope with challenges in the environment, animals must adapt their behavior to acquire rewards and to avoid punishments. Maladaptive changes in the neuromodulatory systems and neural circuits for reward and aversion can lead to manifestation of several prominent psychiatric disorders including addiction and depression. Recent progress is pushing the boundaries of knowledge on two major fronts in research on reward and aversion: First, new layers of complexity have been reported on the functions of dopamine (DA) and serotonin (5-HT) neuromodulatory systems in reward and aversion. Second, specific circuit components in the neural pathways that encode reward and aversion have begun to be identified. This review aims to outline historic perspectives and new insights into the functions of DA and 5-HT systems in coding the distinct components of rewards. It also highlights recent advances in neural circuit studies enabled by new technologies, such as cell-type-specific electrophysiology and tracing, and optogenetics-based behavioral manipulation. This knowledge may provide guidance for developing novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.