bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wave reflections in the pulmonary arteries analysed with the reservoir–wave model
Authors: Bouwmeester J. Christopher , Belenkie Israel , Shrive Nigel G. , Tyberg John V. 
Published: April 2014

Key points
In the pulmonary artery, we use the reservoir–wave model to separate the effects of a charging and discharging, elastic arterial reservoir from the effects of waves created by the contracting and relaxing heart.
Wave intensity analysis quantifies the effects of waves that cause changes in pressure and flow and precisely identifies when waves created by the heart and reflections of these waves start and end.
We show that negative wave reflections arise from the junction of lobar arteries stemming from the left and right pulmonary arteries.
When blood volume is increased and pulmonary arteries become distended, the strength of negative wave reflections increases when 100% O2 is used for ventilation.
Negative reflections suck blood downstream and, as they arrive when the heart is developing maximal pressure, negative reflections help to lower the back pressure the heart must pump against and, thus, they tend to increase the forward flow of blood.
AbstractConventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir–wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end‐expiratory pressure were observed. The reservoir–wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in ‘excess’ quantities, which were treated as wave‐related. Wave intensity analysis quantified the contributions of waves originating upstream (forward‐going waves) and downstream (backward‐going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end‐expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow.
A novel short‐term plasticity of intrinsic excitability in the hippocampal CA1 pyramidal cells
Authors: Sánchez‐Aguilera A. , Sánchez‐Alonso J. L. , Vicente‐Torres M. A. , Colino A. 
Published: April 2014

Key points
Changes in neuronal activity often trigger compensatory mechanisms that stabilize neuron output.
We have identified a novel form of short‐term plasticity of membrane excitability, which develops early after the eye‐opening period in rats.
Holding the membrane potential of CA1 neurons at subthreshold depolarization from 15 s to several minutes induces a reduction of the excitability.
This plasticity requires an influx of T‐type Ca2+ current that modulates the A‐type K+ current.
These results help us understand that the resting potential history could modify cell intrinsic excitability.
AbstractChanges in neuronal activity often trigger compensatory mechanisms aimed at regulating network activity homeostatically. Here we have identified and characterized a novel form of compensatory short‐term plasticity of membrane excitability, which develops early after the eye‐opening period in rats (P16–19 days) but not before that developmental stage (P9–12 days old). Holding the membrane potential of CA1 neurons right below the firing threshold from 15 s to several minutes induced a potentiation of the repolarizing phase of the action potentials that contributed to a decrease in the firing rate of CA1 pyramidal neurons in vitro. Furthermore, the mechanism for inducing this plasticity required the action of intracellular Ca2+ entering through T‐type Ca2+ channels. This increase in Ca2+ subsequently activated the Ca2+ sensor K+ channel interacting protein 3, which led to the increase of an A‐type K+ current. These results suggest that Ca2+ modulation of somatic A‐current represents a new form of homeostatic regulation that provides CA1 pyramidal neurons with the ability to preserve their firing abilities in response to membrane potential variations on a scale from tens of seconds to several minutes.
Amplification of Aminoglycoside Resistance Gene
aphA1
in Acinetobacter baumannii Results in Tobramycin Therapy Failure
Authors: McGann Patrick , Courvalin Patrice , Snesrud Erik , Clifford Robert J. , Yoon Eun-Jeong , Onmus-Leone Fatma , Ong Ana C. , Kwak Yoon I. , Grillot-Courvalin Catherine , Lesho Emil , Waterman Paige E. 
Published: April 2014

ABSTRACT

Gene amplification is believed to play an important role in antibiotic resistance but has been rarely documented in clinical settings because of its unstable nature. We report a rise in MICs from 0.5 to 16 μg/ml in successive
Acinetobacter baumannii
isolated over 4 days from a patient being treated with tobramycin for an infection by multidrug-resistant
A. baumannii
, resulting in therapeutic failure. Isolates were characterized by whole-genome sequencing, real-time and reverse transcriptase PCR, and growth assays to determine the mechanism of tobramycin resistance and its fitness cost. Tobramycin resistance was associated with two amplification events of different chromosomal fragments containing the
aphA1
aminoglycoside resistance gene part of transposon Tn
6020
. The first amplification event involved low amplification (6 to 10 copies) of a large DNA fragment that was unstable and conferred tobramycin MICs of ≤8 μg/ml. The second event involved moderate (10 to 30 copies) or high (40 to 110 copies) amplification of Tn
6020
. High copy numbers were associated with tobramycin MICs of 16 μg/ml, impaired fitness, and genetic instability, whereas lower copy numbers resulted in tobramycin MICs of ≤8 μg/ml and no fitness cost and were stably maintained
in vitro
. Exposure
in vitro
to tobramycin of the initial susceptible isolate and of the
A. baumannii
AB0057 reference strain led to similar
aphA1
amplifications and elevated tobramycin MICs. To the best of our knowledge, this is the first report of
in vivo
development of antibiotic resistance secondary to gene amplifications resulting in therapy failure.

IMPORTANCE
A combination of whole-genome sequencing and mapping were used to detect an antibiotic resistance mechanism, gene amplification, which has been presumed for a long time to be of major importance but has rarely been reported in clinical settings because of its unstable nature. Two gene amplification events in a patient with an
Acinetobacter baumannii
infection treated with tobramycin were identified. One gene amplification event led to high levels of resistance and was rapidly reversible, while the second event led to low and more stable resistance since it incurred low fitness cost on the host. Gene amplification, with an associated rise in tobramycin MICs, could be readily reproduced
in vitro
from initially susceptible strains exposed to increasing concentrations of tobramycin, suggesting that gene amplification in
A. baumannii
may be a more common mechanism than currently believed. This report underscores the importance of rapid molecular techniques for surveillance of drug resistance.
Diverse Antibiotic Resistance Genes in Dairy Cow Manure
Authors: Wichmann Fabienne , Udikovic-Kolic Nikolina , Andrew Sheila , Handelsman Jo 
Published: April 2014

ABSTRACT
Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings.

IMPORTANCE
The increasing prevalence of antibiotic resistance among bacteria is one of the most intractable challenges in 21st-century public health. The origins of resistance are complex, and a better understanding of the impacts of antibiotics used on farms would produce a more robust platform for public policy. Microbiomes of farm animals are reservoirs of antibiotic resistance genes, which may affect distribution of antibiotic resistance genes in human pathogens. Previous studies have focused on antibiotic resistance genes in manures of animals subjected to intensive antibiotic use, such as pigs and chickens. Cow manure has received less attention, although it is commonly used in crop production. Here, we report the discovery of novel and diverse antibiotic resistance genes in the cow microbiome, demonstrating that it is a significant reservoir of antibiotic resistance genes. The genomic resource presented here lays the groundwork for understanding the dispersal of antibiotic resistance from the agroecosystem to other settings.
Maltreatment or violence-related injury in children and adolescents admitted to the NHS: comparison of trends in England and Scotland between 2005 and 2011
Authors: Gonzalez-Izquierdo Arturo , Cortina-Borja Mario , Woodman Jenny , Mok Jacqueline , McGhee Janice , Taylor Julie , Parkin Chloe , Gilbert Ruth 
Published: April 2014

ObjectiveLegislation to safeguard children from maltreatment by carers or violence by others was advanced in England and Scotland around 2004–2005 and resulted in different policies and services. We examined whether subsequent trends in injury admissions to hospital related to maltreatment or violence varied between the two countries.Setting and participantsWe analysed rates of all unplanned injury admission to National Health Service (NHS) hospitals in England and Scotland between 2005 and 2011 for children and adolescents aged less than 19 years.OutcomesWe compared incidence trends for maltreatment or violence-related (MVR) injury and adjusted rate differences between 2005 and 2011 using Poisson or negative binomial regression models to adjust for seasonal effects and secular trends in non-MVR injury. Infants, children 1–10 years and adolescents 11–18 years were analysed separately.ResultsIn 2005, MVR rates were similar in England and Scotland for infants and 1–10-year-olds, but almost twice as high in Scotland for 11–18-year-olds. MVR rates for infants increased by similar amounts in both countries, in line with rising non-MVR rates in England but contrary to declines in Scotland. Among 1–10-year-olds, MVR rates increased in England and declined in Scotland, in line with increasing non-MVR rates in England and declining rates in Scotland. Among 11–18-year-olds, MVR rates declined more steeply in Scotland than in England along with declines in non-MVR trends.ConclusionsDiverging trends in England and Scotland may reflect true changes in the occurrence of MVR injury or differences in the way services recognise and respond to these children, record such injuries or a combination of these factors. Further linkage of data from surveys and services for child maltreatment and violence could help distinguish the impact of policies.
Clinical predictors of 2-year outcome of resective epilepsy surgery in adults with refractory epilepsy: a cohort study
Authors: Kanchanatawan B , Limothai C , Srikijvilaikul T , Maes M 
Published: April 2014

ObjectivesResective epilepsy surgery is currently a standard treatment for intractable epilepsy. Seizure freedom and discontinuation of antiepileptic drugs are the ultimate goals of epilepsy treatment. This study was carried out to delineate (1) possible differences in the success rate of epilepsy surgery 6 and 24 months after surgery; and (2) the clinical predictors of a good response to surgery.SettingThis is a cohort study performed at a tertiary care unit of a university hospital.ParticipantsIn this cohort study, 189 adults with intractable epilepsy who underwent epilepsy surgery were included. We collected clinical data at three time points, that is, preoperative and 6 and 24 months after surgery.Primary and secondary outcome measuresEngel class I–IV classification was the primary outcome measure of epilepsy surgery. The authors statistically adjusted Engel class I–IV classification for postoperative changes in antiepileptic drugs and used this new classification as a secondary outcome variable.ResultsThe success rate was 78.8% 6 months after surgery and increased to 88.3% 24 months after surgery. This success rate was reflected not only by the reduced number of seizures postsurgery, but also by a reduced dosage and use of antiepileptic drugs. Logistic regression analysis showed that a successful outcome of surgery is predicted by having temporal rather than extratemporal lobe epilepsy and less than nine presurgery seizures per month, while a positive familial history of epilepsy, younger age and dysphoric symptoms, the first 3 months after surgery, significantly worsened the outcome of surgery. Duration of illness, age at onset, epilepsy location, type of lesions and the presence of psychosis were not significant in predicting treatment outcome.ConclusionsThese findings have clinical relevance in that a better selection of patients based on the significant clinical predictors will increase the success rate of epilepsy surgery and treatment.
Improving electronic information sharing for palliative care patients
Authors: Pringle Amanda , Finucane Anne , Oxenham David 
Published: April 2014

AbstractCoordination of services used by palliative care patients across care contexts is essential in providing patient centred care.In Lothian, Edinburgh, a baseline audit in 2008 of patients known to all four specialist palliative care teams revealed only 49% had information available to out of hours (OOH) general practitioners (GPs).This highlighted the poor handover and sharing of information, which are essential for providing quality care for palliative patients in accordance with their wishes, and for reducing inappropriate hospital admissions.A number of quality improvement measures have been introduced, some nationally in Scotland, such as the roll out of Electronic Palliative Care Summaries (ePCS) – an electronic register containing up to date information including patient wishes and latest treatment decisions. In addition there have been changes to the GP Quality Outcomes Framework encouraging the use of electronic records. Locally, at Marie Curie Hospice, drivers were implemented including hosting GP education evenings promoting ePCS use, alteration of hospice discharge letter format to complement ePCS completion, in addition to offering specialist nurse support and presence at GP practice palliative care register meetings.A re-audit in 2012 revealed that 75% of specialist palliative care patients had electronic information available to OOH services, and in 2013, 71% of patients. This represents a significant improvement in electronic information sharing across care contexts.Building on the progress of ePCS, a new Electronic Key Information Summary is currently being rolled out across Scotland.This quality improvement report reflects on the positive measures taken to address the important clinical need of effective electronic handover for specialist palliative care patients in Lothian. Furthermore, it highlights the ongoing requirement to continue to improve the quality and availability of electronically shared information for every patient known to palliative care services across care contexts.
Improving Transparency in Teleoperation by Means of Cutaneous Tactile Force Feedback
Authors: Pacchierotti Claudio , Tirmizi Asad , Prattichizzo Domenico 
Published: April 2014

A study on the role of cutaneous and kinesthetic force feedback in teleoperation is presented. Cutaneous cues provide less transparency than kinesthetic force, but they do not affect the stability of the teleoperation system. On the other hand, kinesthesia provides a compelling illusion of telepresence but affects the stability of the haptic loop. However, when employing common grounded haptic interfaces, it is not possible to independently control the cutaneous and kinesthetic components of the interaction. For this reason, many control techniques ensure a stable interaction by scaling down both kinesthetic and cutaneous force feedback, even though acting on the cutaneous channel is not necessary.We discuss here the feasibility of a novel approach. It aims at improving the realism of the haptic rendering, while preserving its stability, by modulating cutaneous force to compensate for a lack of kinesthesia. We carried out two teleoperation experiments, evaluating (1) the role of cutaneous stimuli when reducing kinesthesia and (2) the extent to which an overactuation of the cutaneous channel can fully compensate for a lack of kinesthetic force feedback. Results showed that, to some extent, it is possible to compensate for a lack of kinesthesia with the aforementioned technique, without significant performance degradation. Moreover, users showed a high comfort level in using the proposed system.
Investigation of Gamma and Neutron Shielding Parameters for Borate Glasses Containing NiO and PbO
Authors: Singh Vishwanath P. , Badiger N. M. 
Published: April 2014

The mass attenuation coefficients, μ/ρ, half-value layer, HVL, tenth-value layer, TVL, effective atomic numbers, ZPIeff, and effective electron densities, Ne,eff, of borate glass sample systems of (100-x-y) Na2B4O7 : xPbO : yNiO (where x and y=0, 2, 4, 6, 8, and 10 weight percentage) containing PbO and NiO, with potential gamma ray and neutron shielding applications, have been investigated. The gamma ray interaction parameters, μ/ρ, HVL, TVL, ZPIeff, and Ne,eff, were computed for photon energy range 1 keV–100 GeV. The macroscopic fast neutron removal cross-sections (ΣR) have also been calculated. Appreciable variations were noted for all the interaction parameters by varying the photon energy and the chemical composition of the glass samples. The better shielding properties of borate glass samples containing PbO were found. These results indicated that borate glass samples are a good radiation shielding material.
Comparative Oncogenomics Identifies PSMB4 and SHMT2 as Potential Cancer Driver Genes
Authors: Lee Genee Y. , Haverty Peter M. , Li Li , Kljavin Noelyn M. , Bourgon Richard , Lee James , Stern Howard , Modrusan Zora , Seshagiri Somasekar , Zhang Zemin , Davis David , Stokoe David , Settleman Jeffrey , de Sauvage Frederic J. , Neve Richard M. 
Published: April 2014

AbstractCancer genomes maintain a complex array of somatic alterations required for maintenance and progression of the disease, posing a challenge to identify driver genes among this genetic disorder. Toward this end, we mapped regions of recurrent amplification in a large collection (n = 392) of primary human cancers and selected 620 genes whose expression is elevated in tumors. An RNAi loss-of-function screen targeting these genes across a panel of 32 cancer cell lines identified potential driver genes. Subsequent functional assays identified SHMT2, a key enzyme in the serine/glycine synthesis pathway, as necessary for tumor cell survival but insufficient for transformation. The 26S proteasomal subunit, PSMB4, was identified as the first proteasomal subunit with oncogenic properties promoting cancer cell survival and tumor growth in vivo. Elevated expression of SHMT2 and PSMB4 was found to be associated with poor prognosis in human cancer, supporting the development of molecular therapies targeting these genes or components of their pathways. Cancer Res; 74(11); 3114–26. ©2014 AACR.
Influence of Drug Formulation on OATP1B-Mediated Transport of Paclitaxel
Authors: Nieuweboer Annemieke J.M. , Hu Shuiying , Gui Chunshan , Hagenbuch Bruno , Ghobadi Moghaddam-Helmantel Inge M. , Gibson Alice A. , de Bruijn Peter , Mathijssen Ron H.J. , Sparreboom Alex 
Published: April 2014

Abstract
Taxane antineoplastic agents are extensively taken up into hepatocytes by OATP1B-type transporters before metabolism and excretion. Because the biodistributional properties imposed upon these agents by different solubilizers drive clinically important pharmacodynamic endpoints, we tested the hypothesis that the in vitro and in vivo interaction of taxanes with OATP1B transporters is affected by the choice of drug delivery system. Transport of paclitaxel, docetaxel, and cabazitaxel was studied in vitro using various cell lines transfected with OATP1B1, OATP1B3, or the rodent equivalent OATP1B2. Pharmacokinetic studies were done in wild-type and OATP1B2-knockout mice in the presence or absence of polysorbate 80 (PS80) or Kolliphor EL (formerly Cremophor EL; CrEL). Paclitaxel and docetaxel, but not cabazitaxel, were transported substrates of OATP1B1, OATP1B3, and OATP1B2, and these in vitro transport processes were strongly reduced in the presence of clinically relevant concentrations of PS80 and CrEL. When paclitaxel was administered without any solubilizers, deficiency of OATP1B2 in mice was associated with a significantly decreased systemic clearance because of a liver distribution defect (P = 0.000484). However, this genotype dependence of paclitaxel clearance was masked in the presence of PS80 or CrEL because of significant inhibition of OATP1B2-mediated hepatocellular uptake of the drug (P &lt; 0.05). Our findings confirm the importance of OATP1B-type transporters in the hepatic elimination of taxanes and indicate that this process can be inhibited by PS80 and CrEL. These results suggest that the likelihood of drug–drug interactions mediated by these transporters is strongly dependent on the selected taxane solubilizer. Cancer Res; 74(11); 3137–45. ©2014 AACR.
Molecular Pathways: Niches in Metastatic Dormancy
Authors: Yumoto Kenji , Eber Matthew R. , Berry Janice E. , Taichman Russell S. , Shiozawa Yusuke 
Published: April 2014

Abstract
Despite the best available treatments for primary tumors, cancer can return, even after a long disease-free interval. During this period, cancer cells are believed to lie dormant in either primary sites, metastatic sites, or independent sites like bone marrow, effectively escaping adjuvant cytotoxic treatments. To date, little is known about how these cells transition to dormancy, or how they are reactivated if cancer recurs. Recent studies have revealed the effects of tumor microenvironment or niche on the regulation of tumor dormancy via the signaling pathways of growth arrest–specific 6, bone morphogenetic protein 7, and TGFβ1, and that the balance between activation of p38 MAPK and ERK MAPK plays a pivotal role in tumor dormancy. In this review, we discuss tumor dormancy from the perspective of the niche and consider potential therapeutic targets. Greater understanding of the mechanisms involved will help guide innovation in the care of patients with advanced cancer. Clin Cancer Res; 20(13); 3384–9. ©2014 AACR.