bluuebunny/crossref_metadata_2025 huggingface dataset:
Techniques for Evaluating and Improving the Operational Efficiency of Positive Train Control Braking Enforcement Algorithms
Authors: Brosseau Joe
Published: June 2014

Software algorithms are used in Positive Train Control (PTC) systems to predict train stopping distance and to enforce a penalty brake application. These algorithms have been shown to be overly conservative, leading to operational inefficiencies by interfering with normal train operations. A braking enforcement algorithm that can safely stop trains to prevent authority and speed limit violations without impacting existing railroad operations is critical to successful widespread implementation of PTC.

Due to operational issues observed with early PTC braking enforcement algorithms, a number of techniques are proposed and evaluated to improve the operational efficiency of these algorithms, with emphasis on applicability to PTC systems currently being implemented. Transportation Technology Center, Inc. (TTCI) is employing a new methodology for evaluation of braking algorithms that uses Monte Carlo simulation techniques to statistically evaluate the performance of the algorithm, with limited need for field testing to verify the simulation results. In the Monte Carlo process, computer simulations are run repeatedly using randomly selected input values to predict the resulting probability distribution of stopping locations. The method provides a higher level of confidence in algorithm performance with reduced time and cost compared to traditional methods, which rely heavily on field testing. For freight trains, the method utilizes a detailed train dynamics simulation model previously developed and validated by the Association of American Railroads (AAR). For passenger trains, TTCI is developing and validating a new model capable of simulating brake systems and components specific to passenger and commuter equipment.

New methods for addressing operational efficiency of braking algorithms focus on improving the accuracy of stopping distance prediction and reducing the potential variation from the prediction. Techniques investigated by TTCI include adaptive functions, which measure train braking performance en route and adapt the algorithm to these characteristics; emergency brake backup, which uses feedback following a penalty application to determine if additional emergency braking is required to stop the train short of the target; an improved target offset function, which relies on statistical multi-variable regression of thousands of stopping distance simulations; and including information about dynamic braking effort in the stopping distance prediction. Results from TTCI’s investigations show potential to reduce the operational impact, by demonstrating the probability of stopping excessively short of the target is significantly less than that of previous algorithms. The techniques are already being adopted by PTC onboard suppliers for the largest North American railroads, and many are applicable to railways worldwide.
Stress-gradient induced migration of polymers in corrugated channels
Authors: Tsouka Sophia , Dimakopoulos Yannis , Mavrantzas Vlasis , Tsamopoulos John
Published: June 2014

We study the flow of a dilute polymer solution in a wavy channel under steady-state flow conditions by employing the nonequilibrium thermodynamics two-fluid model [Mavrantzas and Beris, Phys. Rev. Lett. 69, 273–276 (1992)], allowing for the coupling between polymer concentration and polymer stresses. The resulting highly complex system of partial differential equations describing inhomogeneous transport phenomena in the fluid are solved with an efficient implementation of the mixed finite-element method. We present numerical results for polymer concentration, stress, velocity, and fluxes of polymer as a function of the nondimensional parameters of the problem (the Deborah number De, the Peclet number Pe, the Reynolds number Re, the ratio of the solvent viscosity to the total fluid viscosity β, and the constriction ratio of the channel width cr). We find that the constricted part of the wall is depleted of polymer, when the polymer diffusion length scale, expressed by the ratio of De/Pe, increases. The migration is more pronounced for macromolecules characterized by longer relaxation times and takes place toward the expanding part of the channel or toward the centerplane. Migration is also enhanced by the width variability of the channel: The more corrugated the channel, the stronger the transfer of polymer to the centerplane. This increases the spatial extent of polymer depletion near the wall or induces a zone of sharp variation in polymer stress and concentration, which moves away from the channel wall, especially in lower polymer concentration. The development of a polymer-depleted layer smooths out the boundary layer which is known to arise with Boger fluids at the walls of such corrugated channels or tubes and gives rise to an “apparent” slip in the constricted section of the wall and to a very low value of the drag force on the wall. When and where boundary layers arise, they scale as (1/De) for the stresses and as (De/Pe)1/3 for the concentration.
Intact NMDA Receptor Structure Revealed
Authors: Vinson Valda
Published: June 2014

Specific interactions between key neuronal receptor subunits and domains are critical for functional regulation.
Making and Breaking Neuronal Synapses
Authors: Hines Pamela J.
Published: June 2014

Elimination of redundant synapses and formation of functional circuits in developing brain involves axon guidance molecules.
Pinpointing the Pressure Responder
Authors: Gough Nancy R.
Published: June 2014

Optogenetics and knockout mice demonstrate that Merkel cells, a specialized epidermal cell, actively contribute to touch perception.
Studies on the Antileishmanial Mechanism of Action of the Arylimidamide DB766: Azole Interactions and Role of CYP5122A1
Authors: Pandharkar Trupti , Zhu Xiaohua , Mathur Radhika , Jiang Jinmai , Schmittgen Thomas D. , Shaha Chandrima , Werbovetz Karl A.
Published: June 2014

Arylimidamides (AIAs) are inspired by diamidine antimicrobials but show superior activity against intracellular parasites. The AIA DB766 {2,5-bis[2-(2-
i
-propoxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride} displays outstanding potency against intracellular
Leishmania
parasites and is effective in murine and hamster models of visceral leishmaniasis when given orally, but its mechanism of action is unknown. In this study, through the use of continuous DB766 pressure, we raised
Leishmania donovani
axenic amastigotes that displayed 12-fold resistance to this compound. These DB766-resistant (DB766R) parasites were 2-fold more sensitive to miltefosine than wild-type organisms and were hypersensitive to the sterol 14α-demethylase (CYP51) inhibitors ketoconazole and posaconazole (2,000-fold more sensitive and over 12,000-fold more sensitive than the wild type, respectively). Western blot analysis of DB766R parasites indicated that while expression of CYP51 is slightly increased in these organisms, expression of CYP5122A1, a recently identified cytochrome P450 associated with ergosterol metabolism in
Leishmania
, is dramatically reduced in DB766R parasites.
In vitro
susceptibility assays demonstrated that CYP5122A1 half-knockout
L. donovani
promastigotes were significantly less susceptible to DB766 and more susceptible to ketoconazole than their wild-type counterparts, consistent with observations in DB766R parasites. Further, DB766-posaconazole combinations displayed synergistic activity in both axenic and intracellular
L. donovani
amastigotes. Taken together, these studies implicate CYP5122A1 in the antileishmanial action of the AIAs and suggest that DB766-azole combinations are potential candidates for the development of synergistic antileishmanial therapy.
Complete Sequencing of IncI1 Sequence Type 2 Plasmid pJIE512b Indicates Mobilization of
bla
CMY-2
from an IncA/C Plasmid
Authors: Tagg Kaitlin A. , Iredell Jonathan R. , Partridge Sally R.
Published: June 2014

Sequencing of pJIE512b, a 92.3-kb IncI1 sequence type 2 (ST2) plasmid carrying
bla
CMY-2
, revealed a
bla
CMY-2
context that appeared to have been mobilized from an IncA/C plasmid by the insertion sequence IS
1294
. A comparison with published plasmids suggests that
bla
CMY-2
has been mobilized from IncA/C to IncI1 plasmids more than once by IS
1294
-like elements. Alignment of pJIE512b with the only other available IncI1 ST2 plasmid revealed differences across the backbones, indicating variability within this sequence type.
Preclinical Studies of Amixicile, a Systemic Therapeutic Developed for Treatment of Clostridium difficile Infections That Also Shows Efficacy against Helicobacter pylori
Authors: Hoffman Paul S. , Bruce Alexandra M. , Olekhnovich Igor , Warren Cirle A. , Burgess Stacey L. , Hontecillas Raquel , Viladomiu Monica , Bassaganya-Riera Josep , Guerrant Richard L. , Macdonald Timothy L.
Published: June 2014

Amixicile shows efficacy in the treatment of
Clostridium difficile
infections (CDI) in a mouse model, with no recurrence of CDI. Since amixicile selectively inhibits the action of a B vitamin (thiamine pyrophosphate) cofactor of pyruvate:ferredoxin oxidoreductase (PFOR), it may both escape mutation-based drug resistance and spare beneficial probiotic gut bacteria that do not express this enzyme. Amixicile is a water-soluble derivative of nitazoxanide (NTZ), an antiparasitic therapeutic that also shows efficacy against CDI in humans. In comparative studies, amixicile showed no toxicity to hepatocytes at 200 μM (NTZ was toxic above 10 μM); was not metabolized by human, dog, or rat liver microsomes; showed equivalence or superiority to NTZ in cytochrome P450 assays; and did not activate efflux pumps (breast cancer resistance protein, P glycoprotein). A maximum dose (300 mg/kg) of amixicile given by the oral or intraperitoneal route was well tolerated by mice and rats. Plasma exposure (rats) based on the area under the plasma concentration-time curve was 79.3 h · μg/ml (30 mg/kg dose) to 328 h · μg/ml (100 mg/kg dose), the maximum concentration of the drug in serum was 20 μg/ml, the time to the maximum concentration of the drug in serum was 0.5 to 1 h, and the half-life was 5.6 h. Amixicile did not concentrate in mouse feces or adversely affect gut populations of
Bacteroides
species,
Firmicutes
, segmented filamentous bacteria, or
Lactobacillus
species. Systemic bioavailability was demonstrated through eradication of
Helicobacter pylori
in a mouse infection model. In summary, the efficacy of amixicile in treating CDI and other infections, together with low toxicity, an absence of mutation-based drug resistance, and excellent drug metabolism and pharmacokinetic metrics, suggests a potential for broad application in the treatment of infections caused by PFOR-expressing microbial pathogens in addition to CDI.
Improved Detection of Emerging Drug-Resistant Mutant Cytomegalovirus Subpopulations by Deep Sequencing
Authors: Chou Sunwen , Ercolani Ronald J. , Sahoo Malaya K. , Lefterova Martina I. , Strasfeld Lynne M. , Pinsky Benjamin A.
Published: June 2014

In immunosuppressed hosts, the development of multidrug resistance complicates the treatment of cytomegalovirus (CMV) infection. Improved genotypic detection of impending drug resistance may follow from recent technical advances. A severely T-cell-depleted patient with chronic lymphocytic leukemia developed CMV pneumonia and high plasma viral loads that were poorly responsive to antiviral therapy. Serial plasma specimens were analyzed for mutant viral populations by conventional and high-throughput deep-sequencing methods. Uncharacterized mutations were phenotyped for drug resistance using recombinant viruses. Conventional genotyping detected viruses with the UL97 kinase substitution C607Y after ganciclovir treatment, a transient subpopulation of UL54 polymerase L773V mutants first detected 8 weeks after foscarnet was started, and a subpopulation of a mutant with deletion of UL54 codons 981 and 982 2 months after the addition of cidofovir. Deep sequencing of the same serial specimens revealed the same UL54 mutants sooner, along with a more complex evolution of known and newly recognized mutant subpopulations missed by conventional sequencing. The UL54 exonuclease substitutions D413N, K513R, and C539G were newly shown to confer ganciclovir-cidofovir resistance, while L773V was shown to confer foscarnet resistance and add to the ganciclovir resistance conferred by UL97 C607Y. Increased sequencing depth provided a more timely and detailed diagnosis of mutant viral subpopulations that evolved with changing anti-CMV therapy.
Posaconazole Concentrations in Human Tissues after Allogeneic Stem Cell Transplantation
Authors: Blennow Ola , Eliasson Erik , Pettersson Tommy , Pohanka Anton , Szakos Attila , El-Serafi Ibrahim , Hassan Moustapha , Ringdén Olle , Mattsson Jonas
Published: June 2014

Few data have been published regarding posaconazole tissue concentrations in humans. We analyzed tissue concentrations in biopsy specimens taken at autopsy from seven patients who received posaconazole prophylaxis because of graft-versus-host disease. The results were compared to plasma concentrations collected before death. Tissue concentrations suggestive of an accumulation of posaconazole were found in the heart, lung, liver, and kidney but not in the brain.
Role of FKS Mutations in Candida glabrata: MIC Values, Echinocandin Resistance, and Multidrug Resistance
Authors: Pham Cau D. , Iqbal Naureen , Bolden Carol B. , Kuykendall Randall J. , Harrison Lee H. , Farley Monica M. , Schaffner William , Beldavs Zintars G. , Chiller Tom M. , Park Benjamin J. , Cleveland Angela A. , Lockhart Shawn R.
Published: June 2014

Candida glabrata
is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of
C. glabrata
disease due to the high rate of resistance to fluconazole. Recent case reports indicate that
C. glabrata
resistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates of
C. glabrata
collected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions of
FKS1
and
FKS2
, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 in
FKS1
and 35 in
FKS2
. All of the isolates with an
FKS
mutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S.
C. glabrata
isolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S.
C. glabrata
isolates for echinocandin resistance is warranted.
The Pseudomonas aeruginosa Diguanylate Cyclase GcbA, a Homolog of P. fluorescens GcbA, Promotes Initial Attachment to Surfaces, but Not Biofilm Formation, via Regulation of Motility
Authors: Petrova Olga E. , Cherny Kathryn E. , Sauer Karin
Published: June 2014

Cyclic di-GMP is a conserved signaling molecule regulating the transitions between motile and sessile modes of growth in a variety of bacterial species. Recent evidence suggests that
Pseudomonas
species harbor separate intracellular pools of c-di-GMP to control different phenotypic outputs associated with motility, attachment, and biofilm formation, with multiple diguanylate cyclases (DGCs) playing distinct roles in these processes, yet little is known about the potential conservation of functional DGCs across
Pseudomonas
species. In the present study, we demonstrate that the
P. aeruginosa
homolog of the
P. fluorescens
DGC GcbA involved in promoting biofilm formation via regulation of swimming motility likewise synthesizes c-di-GMP to regulate surface attachment via modulation of motility, however, without affecting subsequent biofilm formation.
P. aeruginosa
GcbA was found to regulate flagellum-driven motility by suppressing flagellar reversal rates in a manner independent of viscosity, surface hardness, and polysaccharide production.
P. fluorescens
GcbA was found to be functional in
P. aeruginosa
and was capable of restoring phenotypes associated with inactivation of
gcbA
in
P. aeruginosa
to wild-type levels. Motility and attachment of a
gcbA
mutant strain could be restored to wild-type levels via overexpression of the small regulatory RNA RsmZ. Furthermore, epistasis analysis revealed that while both contribute to the regulation of initial surface attachment and flagellum-driven motility, GcbA and the phosphodiesterase DipA act within different signaling networks to regulate these processes. Our findings expand the complexity of c-di-GMP signaling in the regulation of the motile-sessile switch by providing yet another potential link to the Gac/Rsm network and suggesting that distinct c-di-GMP-modulating signaling pathways can regulate a single phenotypic output.
Transcription Start Site Sequence and Spacing between the −10 Region and the Start Site Affect Reiterative Transcription-Mediated Regulation of Gene Expression in Escherichia coli
Authors: Han Xiaosi , Turnbough Charles L.
Published: June 2014

Reiterative transcription is a reaction catalyzed by RNA polymerase, in which nucleotides are repetitively added to the 3′ end of a nascent transcript due to upstream slippage of the transcript without movement of the DNA template. In
Escherichia coli
, the expression of several operons is regulated through mechanisms in which high intracellular levels of UTP promote reiterative transcription that adds extra U residues to the 3′ end of a nascent transcript during transcription initiation. Immediately following the addition of one or more extra U residues, the nascent transcripts are released from the transcription initiation complex, thereby reducing the level of gene expression. Therefore, gene expression can be regulated by internal UTP levels, which reflect the availability of external pyrimidine sources. The magnitude of gene regulation by these mechanisms varies considerably, even when control mechanisms are analogous. These variations apparently are due to differences in promoter sequences. One of the operons regulated (in part) by UTP-sensitive reiterative transcription in
E. coli
is the
carAB
operon, which encodes the first enzyme in the pyrimidine nucleotide biosynthetic pathway. In this study, we used the
carAB
operon to examine the effects of nucleotide sequence at and near the transcription start site and spacing between the start site and −10 region of the promoter on reiterative transcription and gene regulation. Our results indicate that these variables are important determinants in establishing the extent of reiterative transcription, levels of productive transcription, and range of gene regulation.
β-Alanine Biosynthesis in Methanocaldococcus jannaschii
Authors: Wang Yu , Xu Huimin , White Robert H.
Published: June 2014

One efficient approach to assigning function to unannotated genes is to establish the enzymes that are missing in known biosynthetic pathways. One group of such pathways is those involved in coenzyme biosynthesis. In the case of the methanogenic archaeon
Methanocaldococcus jannaschii
as well as most methanogens, none of the expected enzymes for the biosynthesis of the β-alanine and pantoic acid moieties required for coenzyme A are annotated. To identify the gene(s) for β-alanine biosynthesis, we have established the pathway for the formation of β-alanine in this organism after experimentally eliminating other known and proposed pathways to β-alanine from malonate semialdehyde,
l
-alanine, spermine, dihydrouracil, and acryloyl-coenzyme A (CoA). Our data showed that the decarboxylation of aspartate was the only source of β-alanine in cell extracts of
M. jannaschii
. Unlike other prokaryotes where the enzyme producing β-alanine from
l
-aspartate is a pyruvoyl-containing
l
-aspartate decarboxylase (PanD), the enzyme in
M. jannaschii
is a pyridoxal phosphate (PLP)-dependent
l
-aspartate decarboxylase encoded by MJ0050, the same enzyme that was found to decarboxylate tyrosine for methanofuran biosynthesis. A

K
m

of ∼0.80 mM for
l
-aspartate with a specific activity of 0.09 μmol min
−1
mg
−1
at 70°C for the decarboxylation of
l
-aspartate was measured for the recombinant enzyme. The MJ0050 gene was also demonstrated to complement the
Escherichia coli
panD
deletion mutant cells, in which
panD
encoding aspartate decarboxylase in
E. coli
had been knocked out, thus confirming the function of this gene
in vivo
.
Treatment of choroidal neovascularisation secondary to membranoproliferative glomerulonephritis type II with intravitreal ranibizumab
Authors: McCullagh Donal , Silvestri Giuliana , Maxwell Alexander P
Published: June 2014

Membranoproliferative glomerulonephritis type II (MPGN II) is characterised by electron-dense deposits of complement components in the glomerular basement membrane and retinal pigment epithelium. Approximately, 10% of affected individuals develop serious ocular complications similar to age-related macular degeneration such as choroidal neovascularisation (CNV), which has been managed with photocoagulation or photodynamic therapy; however, these treatments can impact visual acuity. We report the case of a 42-year-old woman with MPGN II presenting with decreased visual acuity and paracentral scotoma in her left eye due to an extrafoveal choroidal neovascular membrane (growth of new vessels under the retina). The patient was successfully treated with intravitreal ranibizumab (Lucentis) with restoration of visual function. This case highlights the successful management of CNV secondary to MPGN II with the antivascular endothelial growth factor agent ranibizumab and emphasises the importance of early referral of patients with MPGN II who are reporting of visual ‘distortion’.
Lesser trochanter fracture: the presenting feature of a more sinister pathology
Authors: Fox Thomas Peter , Lakkol Sandeshkumar , Oliver Govind
Published: June 2014

We report the rare case of a 75-year-old man who was hospitalised following referral by his general practitioner with a 4-day history of worsening groin pain. Initial radiographs demonstrated an isolated avulsion fracture of the lesser trochanter. There were associated bony changes indicating pathological bone disease, likely secondary to bony metastasis. Further investigation revealed a renal mass almost certainly consistent with a renal cell carcinoma. This case emphasises the importance of having a high index of suspicion for neoplastic pathology when low impact injuries result in fractures.
Acute onset of bilateral visual loss during sildenafil therapy in a young infant with congenital heart disease
Authors: Gaffuri Marcella , Cristofaletti Alessandra , Mansoldo Caterina , Biban Paolo
Published: June 2014

We report a case of posterior non-arteritic ischaemic optic neuropathy (NAION) causing bilateral visual loss in a 7-month-old female infant, after a therapeutic course with sildenafil, a phosphodiesterase type 5 inhibitors (PDE5i). The patient was affected by a complex cyanotic congenital heart defect and had undergone cavopulmonary anastomosis (Glenn operation) 3 months ago. After 2 months of recurring chylothorax, a course of oral sildenafil was administered, with the hypothesis that pulmonary vascular resistances were increased. Approximately 4 weeks later the acute onset of visual worsening and poor pupillary light reflex prompted the diagnosis of posterior NAION. Despite a rapid cessation of PDE5i and systemic treatment with corticosteroids, no visual recovery was noticed at 2-year follow-up. NAION has been associated with PDE5i therapy in adults, but to the best of our knowledge it is almost unheard of in children. We suggest close monitoring of visual function in children undergoing treatment with sildenafil.
An incidental finding of a nodal recurrence of cutaneous malignant melanoma after a 45-year disease-free period
Authors: Goodenough Jenny , Cozon Caroline Louise , Liew Se Hwang
Published: June 2014

We report the case of an 84-year-old woman who had a nodal recurrence of melanoma 45 years after the primary diagnosis of an extremity cutaneous melanoma. It is believed to be the longest disease-free latency period reported between primary melanoma diagnosis and recurrence to date. Late recurrences of melanoma are rare and recurrence after four decades extremely rare. This article suggests melanoma is a disease with a potentially lifelong risk of recurrence and thus clinicians and patients must be vigilant and aware of this risk, particularly if late recurrences are to be recognised early and management optimised.
Breathless after bypass
Authors: Pearse Simon G , Missouris Constantinos , Qureshi Muhammad Ali
Published: June 2014

A 65-year-old normotensive, non-athletic man presented to the cardiology clinic with exertional dyspnoea and chest discomfort. Echocardiography revealed mild left ventricular hypertrophy with good systolic function but with regional wall motion abnormalities suggesting ischaemia. Coronary angiography showed significant three-vessel disease. He underwent coronary artery bypass surgery, which was complicated by recurrent pericardial and pleural effusions, requiring a pericardial window procedure. Over the following year he became increasingly oedematous and breathless. On ECG the complexes were low voltage with impaired R wave progression and atrial fibrillation. Echocardiography revealed progression of the left ventricular hypertrophy (LVH) with a bright myocardium and restrictive filling pattern. MRI scanning confirmed the diagnosis of cardiac amyloidosis. He was referred for transplant but was considered unsuitable due to extensive mediastinal scarring. This case demonstrates the importance of a high index of suspicion for amyloidosis, especially in patients with unexplained LVH. Cardiac MRI or biopsy may expedite the diagnosis.
Severe lactic acidosis and multiorgan failure due to thiamine deficiency during total parenteral nutrition
Authors: Ramsi Musaab , Mowbray Claire , Hartman Gary , Pageler Natalie
Published: June 2014

A 16-year-old perioperative paediatric patient presented with refractory lactic acidosis and multiorgan failure due to thiamine-deficient total parenteral nutrition during a recent national multivitamin shortage. Urgent empiric administration of intravenous thiamine resulted in prompt recovery from this life-threatening condition. Despite readily available treatment, a high index of suspicion is required to prevent cardiovascular collapse and mortality.
Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation
Authors: Cameron Chris , Coyle Doug , Richter Trevor , Kelly Shannon , Gauthier Kasandra , Steiner Sabine , Carrier Marc , Coyle Kathryn , Bai Annie , Moulton Kristen , Clifford Tammy , Wells George
Published: June 2014

Objective

To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0–3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.

Design

Systematic review and network meta-analysis.

Data sources

A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014.

Eligibility criteria for selecting studies

Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy.

Results

For stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA.

Conclusions

Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required.

Systematic review registration number

PROSPERO registry—CRD42012002721.
Criminalisation of clients: reproducing vulnerabilities for violence and poor health among street-based sex workers in Canada—a qualitative study
Authors: Krüsi A , Pacey K , Bird L , Taylor C , Chettiar J , Allan S , Bennett D , Montaner J S , Kerr T , Shannon K
Published: June 2014

Objectives

To explore how criminalisation and policing of sex buyers (clients) rather than sex workers shapes sex workers’ working conditions and sexual transactions including risk of violence and HIV/sexually transmitted infections (STIs).

Design

Qualitative and ethnographic study triangulated with sex work-related violence prevalence data and publicly available police statistics.

Setting

Vancouver, Canada, provides a unique opportunity to evaluate the impact of policies that criminalise clients as the local police department adopted a sex work enforcement policy in January 2013 that prioritises sex workers’ safety over arrest, while continuing to target clients.

Participants

26 cisgender and 5 transgender women who were street-based sex workers (n=31) participated in semistructured interviews about their working conditions. All had exchanged sex for money in the previous 30 days in Vancouver.

Outcome measures

Thematic analysis of interview transcripts and ethnographic field notes focused on how police enforcement of clients shaped sex workers’ working conditions and sexual transactions, including risk of violence and HIV/STIs, over an 11-month period postpolicy implementation (January–November 2013).

Results

Sex workers’ narratives and ethnographic observations indicated that while police sustained a high level of visibility, they eased charging or arresting sex workers and showed increased concern for their safety. However, participants’ accounts and police statistics indicated continued police enforcement of clients. This profoundly impacted the safety strategies sex workers employed. Sex workers continued to mistrust police, had to rush screening clients and were displaced to outlying areas with increased risks of violence, including being forced to engage in unprotected sex.

Conclusions

These findings suggest that criminalisation and policing strategies that target clients reproduce the harms created by the criminalisation of sex work, in particular, vulnerability to violence and HIV/STIs. The current findings support decriminalisation of sex work to ensure work conditions that support the health and safety of sex workers in Canada and globally.
Pain education to prevent chronic low back pain: a study protocol for a randomised controlled trial
Authors: Traeger Adrian C , Moseley G Lorimer , Hübscher Markus , Lee Hopin , Skinner Ian W , Nicholas Michael K , Henschke Nicholas , Refshauge Kathryn M , Blyth Fiona M , Main Chris J , Hush Julia M , Pearce Garry , McAuley James H
Published: June 2014

Introduction

Low back pain (LBP) is the leading cause of disability worldwide. Of those patients who present to primary care with acute LBP, 40% continue to report symptoms 3 months later and develop chronic LBP. Although it is possible to identify these patients early, effective interventions to improve their outcomes are not available. This double-blind (participant/outcome assessor) randomised controlled trial will investigate the efficacy of a brief educational approach to prevent chronic LBP in ‘at-risk’ individuals.

Methods/analysis

Participants will be recruited from primary care practices in the Sydney metropolitan area. To be eligible for inclusion participants will be aged 18–75 years, with acute LBP (<4 weeks’ duration) preceded by at least a 1 month pain-free period and at-risk of developing chronic LBP. Potential participants with chronic spinal pain and those with suspected serious spinal pathology will be excluded. Eligible participants who agree to take part will be randomly allocated to receive 2×1 h sessions of pain biology education or 2×1 h sessions of sham education from a specially trained study physiotherapist. The study requires 101 participants per group to detect a 1-point difference in pain intensity 3 months after pain onset. Secondary outcomes include the incidence of chronic LBP, disability, pain intensity, depression, healthcare utilisation, pain attitudes and beliefs, global recovery and recurrence and are measured at 1 week post-intervention, and at 3, 6 and 12 months post LBP onset.

Ethics/dissemination

Ethical approval was obtained from the University of New South Wales Human Ethics Committee in June 2013 (ref number HC12664). Outcomes will be disseminated through publication in peer-reviewed journals and presentations at international conference meetings.

Trial registration number

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001180808
Did compulsory wear regulations increase personal flotation device (PFD) use by boaters in small power recreational vessels? A before-after observational study conducted in Victoria, Australia
Authors: Cassell Erin , Newstead Stuart
Published: June 2014

Objective

To estimate the effect of the 2005 Victorian mandatory personal flotation device (PFD) wearing regulations on PFD use by occupants of small (hull length ≤4.8 m) power recreational vessels.

Design

Before-after observational study investigating the probability of PFD use among occupants of small vessels before and after the regulations were introduced compared with the probability of use by their counterparts on large power vessels (hull length >4.8–12 m) who were not required to wear PFDs before or after the regulations were introduced in the low-risk conditions in which observations occurred.

Methods

Statewide observation surveys of boaters were conducted in peak boating periods between January and March 2005 (prelegislation) and 2007 (postlegislation). Data collection included size of vessel, age and sex of boaters, life jacket use, boat type, activity of boaters, type of waterway and weather and water conditions. Logistic regression modelling tested whether there were statistically significant differences in the change in the relative odds of occupants wearing PFDs from the preintervention to the postintervention period in small compared with large power recreational vessels.

Results

The probability of PFD use increased from 22% to 63% on small power vessels compared with 12% to 13% on large vessels. Regression analysis showed a high statistically significant increase in the odds of PFD use on small vessels relative to large vessels (OR 6.2, 95% CI 4.2 to 9.3, p<0.001). No statistically significant effect on use on large vessels was associated with the regulation (OR 1.27, 95% CI 0.94 to 1.70, p=0.15). Relative to large vessels, on small vessels the odds of PFD use increased significantly in both sexes, all age groups, all vessel types and activity groupings except for towed water sports where the increase was only marginally statistically significant.

Conclusions

The legislative intervention was successful in increasing PFD wearing in small vessels. However, visible enforcement and tougher penalties are needed to optimise compliance.
Analysis of short-term total hospital costs and current primary cost drivers of coiling versus clipping for unruptured intracranial aneurysms
Authors: Duan Yifei , Blackham Kristine , Nelson Jeff , Selman Warren , Bambakidis Nicholas
Published: June 2014

Background

No randomized controlled trial has successfully compared outcomes between endovascular coiling and microsurgical clipping for unruptured intracranial aneurysms (UIAs).

Objective

To perform a cost comparison between index hospitalizations of patients with UIAs treated with coil embolization or surgical clipping to identify the current primary drivers of costs of either management approach.

Methods

We obtained index hospitalization costs for 125 cases of UIAs treated with coiling or clipping from 2010 to 2012 at our institution. Comparisons were stratified based on patient age, gender, aneurysm size, and aneurysm location. Using linear regressions, we identified clinical parameters that drive total hospital costs.

Results

69 cases were treated with clipping and 56 cases were treated with coiling. Morbidity and length of stay for patients treated with clipping was higher. Total hospital costs and variable direct costs for clipping were significantly lower than for coiling (p=0.003, p<0.001, respectively). Fixed direct costs and fixed indirect costs for clipping were higher than for coiling (p<0.001, p<0.001, respectively). Variable direct costs comprised 50.5% and 68.6% of total hospital costs for clipping and coiling, respectively (p<0.001). Length of stay, aneurysm size, and patient age drove total hospital costs for clipping. Length of stay was a weak driver of total hospital costs for coiling.

Conclusions

Total index hospitalization costs for clipping are lower than for coiling. Costs of clipping and coiling are driven by different clinical variables. The cost of coils and devices is the predominant contributor to the higher total costs of coiling.
Bidirectional promoter trapping T-DNA for insertional mutagenesis in Verticillium dahliae
Authors: Deng Sheng , Wang Cai-yue , Zhang Xin , Lin Ling
Published: June 2014

Transfer DNA (T-DNA)-based random insertional mutagenesis is a universal forward genetic approach for gene identification and cloning in many phytopathogenic fungi. In a large number of randomly selected transformants, screening for mutants with a specific phenotype is laborious, especially for pathogenicity-defective mutants. To accelerate mutant screening and gene identification, a bidirectional promoter-trapping Ti binary vector, 1300-bisGFP-hyg, was constructed and deployed in this study. More than 6000 Verticillium dahliae transformants were obtained by the mediation of Agrobacterium tumefaciens carrying the vector. One thousand randomly selected transformants were cultured on Czapek–Dox and on Czapek–Dox plus cotton root extract media plates. The cultured transformants with green fluorescent protein (GFP) expression or changes in phenotype were selected and used in virulence or promoter-trapping assays. Based on the virulence assay of 60 transformants, the pathogenicity of 17 of these mutants was compromised. Ten pathogenicity-defective mutants were found with GFP expression, and 6 with expression in Czapek–Dox plus cotton root extract media specifically. Using TAIL-PCR (thermal asymmetric interlaced polymerase chain reaction), the T-DNA insertion sites were identified in 8 GFP-expressing transformants, including 5 pathogenicity-defective mutants and 3 unaffected transformants. Promoters of 6 genes were successfully trapped using the T-DNA method in this study. The nonpathogenic transformant 24C9 was the subject of additional investigation. It displayed strong GFP expression on water agar medium supplemented with cotton root extracts and on cotton seedling stems. The results obtained by Southern blot and quantitative real-time PCR confirmed that the transcription level of VdUGPU (encoding UTP-glucose-1-phosphate uridylyltransferase) was significantly reduced owing to T-DNA insertion in the gene promoter region. These results indicate that the bidirectional promoter-trapping Ti vector, combined with induction medium that contains root exudates, can be useful for identification of pathogenicity-related and functional genes in V. dahliae.
Targeting type 2 diabetes: lessons from a knockout model of insulin receptor substrate 2
Authors: Oliveira Joana Moitinho , Rebuffat Sandra A. , Gasa Rosa , Gomis Ramon
Published: June 2014

Insulin receptor substrate 2 (IRS2) is a widely expressed protein that regulates crucial biological processes including glucose metabolism, protein synthesis, and cell survival. IRS2 is part of the insulin – insulin-like growth factor (IGF) signaling pathway and mediates the activation of the phosphotidylinositol 3-kinase (PI3K)–Akt and the Ras–mitogen-activated protein kinase (MAPK) cascades in insulin target tissues and in the pancreas. The best evidence of this is that systemic elimination of the Irs2 in mice (Irs2−/−) recapitulates the pathogenesis of type 2 diabetes (T2D), in that diabetes arises as a consequence of combined insulin resistance and beta-cell failure. Indeed, work using this knockout mouse has confirmed the importance of IRS2 in the control of glucose homeostasis and especially in the survival and function of pancreatic beta-cells. These studies have shown that IRS2 is critically required for beta-cell compensation in conditions of increased insulin demand. Importantly, islets isolated from T2D patients exhibit reduced IRS2 expression, which supports the likely contribution of altered IRS2-dependent signaling to beta-cell failure in human T2D. For all these reasons, the Irs2−/− mouse has been and will be essential for elucidating the inter-relationship between beta-cell function and insulin resistance, as well as to delineate therapeutic strategies to protect beta-cells during T2D progression.
Effects of financial crisis on the industry sector of Chinese stock market — from a perspective of complex network
Authors: Yang Chunxia , Chen Yanhua , Hao Weiwei , Shen Ying , Tang Minxuan , Niu Lei
Published: June 2014

In this paper, we use mutual information to measure the statistical interdependence between 23 industry sectors of Shanghai stock market and construct corresponding correlation network to analyze the shock of 2008 financial crisis on industry sectors. The obtained meaningful facts are as follows. First, such crisis has only a limited impact on leading industries such as Manufacturing, Commercial trade and Machinery & Equipment, which still play an important role in Chinese economy. Second, the crisis badly attacks China's export industries like Electronics, Wood & Furniture and Textile & Clothing. The damage further hurts other industries, and then export industries' influence becomes larger. Third, the crisis adversely impacts the import industries like Petrochemical, Metal & Nonmetal and Pharmaceutical Biotechnology. While due to the stimulation of macroeconomic policies, the influence of crisis on import industries is limited. Similarly, due to relatively strict capital control and the macroeconomic policies stimulating the domestic demand, those industries like Construction, Real Estate and Financial Services are slightly wounded. All these findings suggest that Chinese government should transform from the external demand to the domestic consumption to sustain economic growth.
Near consensus complex linear and nonlinear social networks
Authors: Ling Bingo Wing-Kuen , Ho Charlotte Yuk-Fan , Wang Lidong , Teo Kok-Lay , Tse Chi K. , Dai Qingyun
Published: June 2014

Some of the nodes of complex social networks may support for a given proposal, while the rest of the nodes may be against the given proposal. Even though all the nodes support for or are against the given proposal, the decision certitudes of individual nodes may be different. In this case, the steady state values of the decision certitudes of the majority of the nodes are either higher than or lower than a threshold value. Deriving the near consensus property is a key to the analysis of the behaviors of complex social networks. So far, no result on the behaviors of the complex social networks satisfying the near consensus property has been reported. Hence, it is useful to extend the definition of the exact consensus property to that of a near consensus property and investigate the behaviors of the complex social networks satisfying the near consensus property. This paper extends the definition of exact consensus complex social networks to that of near consensus complex social networks. For complex linear social networks, this paper investigates the relationships among the vectors representing the steady state values of the decision certitudes of the nodes, the influence weight matrix and the set of vectors representing the initial state values of the decision certitudes of the nodes under a given near consensus specification. The above analysis is based on the Eigen theory. For complex nonlinear social networks with certain types of nonlinearities, the relationship between the influence weight matrix and the vectors representing the steady state values of the decision certitudes of the nodes is studied. When a complex nonlinear social network does not achieve the exact consensus property, the optimal near consensus condition that the complex social network can achieve is derived. This problem is formulated as an optimization problem. The total number of nodes that the decision certitudes of the nodes are either higher than or lower than a threshold value is maximized subject to the corresponding near consensus specification. The optimization problem is a nonsmooth optimization problem. The nonsmooth constraints are first approximated by smooth constraints. Then, the approximated optimization problem is solved via a conventional smooth optimization approach. Computer numerical simulation results as well as the comparisons of the behaviors of complex nonlinear social networks to those of the complex linear social networks are presented. The obtained results demonstrate that some complex social networks can satisfy the near consensus property but not the exact consensus property. Also, the conditions for the near consensus property are dependent on the types of nonlinearities, the influence weight matrix and the vectors representing the initial state values of the decision certitudes of the nodes.
Well-posedness and long-time behavior for the modified phase-field crystal equation
Authors: Grasselli Maurizio , Wu Hao
Published: June 2014

We consider a modification of the so-called phase-field crystal (PFC) equation introduced by K. R. Elder et al. This variant has recently been proposed by P. Stefanovic et al. to distinguish between elastic relaxation and diffusion time scales. It consists of adding an inertial term (i.e. a second-order time derivative) into the PFC equation. The mathematical analysis of the resulting equation is more challenging with respect to the PFC equation, even at the well-posedness level. Moreover, its solutions do not regularize in finite time as in the case of PFC equation. Here we analyze the modified PFC (MPFC) equation endowed with periodic boundary conditions. We first prove the global existence and uniqueness of a solution with initial data in a bounded energy space. This solution satisfies some uniform dissipative estimates which allow us to study the long-time behavior of the corresponding dynamical system. In particular, we establish the existence of the global attractor as well as an exponential attractor. Then we demonstrate that any trajectory originating from the bounded energy phase space converges to a single equilibrium. This is done by means of a suitable version of the Łojasiewicz–Simon inequality. An estimate on the convergence rate is also given.