bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caprine Abscess Model of Tulathromycin Concentrations in Interstitial Fluid from Tissue Chambers Inoculated with Corynebacterium pseudotuberculosis following Subcutaneous or Intrachamber Administration
Authors: Washburn K. E. , Fajt V. R. , Lawhon S. D. , Adams L. G. , Tell L. A. , Bissett W. T. 
Published: October 2013

ABSTRACT

Corynebacterium pseudotuberculosis
causes chronic, suppurative, abscessing conditions in livestock and humans. We used an
in vivo
model to evaluate antimicrobial efficacy for focal abscesses caused by
C. pseudotuberculosis
. Tissue chambers were surgically implanted in the subcutaneous tissues of the right and left paralumbar fossa of 12 goats to serve as a model for isolated, focal abscesses. For each goat, one tissue chamber was inoculated with
C. pseudotuberculosis
, while the contralateral chamber served as an uninoculated control. Six goats were administered a single dose of tulathromycin at 2.5 mg/kg of body weight subcutaneously, while the other six received the same dose by injection directly into the inoculated chambers. Our objective was to compare the effects and tulathromycin concentrations in interstitial fluid (IF) samples collected from
C. pseudotuberculosis
-infected and control chambers following subcutaneous or intrachamber injection of tulathromycin. In addition, the effects of tulathromycin on the quantity of
C. pseudotuberculosis
reisolated from inoculated chambers were assessed over time. Tulathromycin IF concentrations from
C. pseudotuberculosis
-infected and control tissue chambers were similar to those in plasma following subcutaneous administration. Following intrachamber administration, tulathromycin IF concentrations in infected chambers were continuously above the MIC for the
C. pseudotuberculosis
isolate for 15 days. There were no significant differences for plasma area under the curve and elimination half-lives between subcutaneous and intrachamber administration. Six of the 12 infected chambers had no growth of
C. pseudotuberculosis
15 days postadministration. Results of this study indicate that tulathromycin may be beneficial in the treatment of focal infections such as those caused by
C. pseudotuberculosis
.
CD4
+
T Cells Drive Goblet Cell Depletion during Citrobacter rodentium Infection
Authors: Chan Justin M. , Bhinder Ganive , Sham Ho Pan , Ryz Natasha , Huang Tina , Bergstrom Kirk S. , Vallance Bruce A. 
Published: October 2013

ABSTRACT

Both idiopathic and infectious forms of colitis disrupt normal intestinal epithelial cell (IEC) proliferation and differentiation, although the mechanisms involved remain unclear. Recently, we demonstrated that infection by the attaching and effacing murine pathogen
Citrobacter rodentium
leads to a significant reduction in colonic goblet cell numbers (goblet cell depletion). This pathology depends on T and/or B cells, as
Rag1
−/−
mice do not suffer this depletion during infection, instead suffering high mortality rates. To address the immune mechanisms involved, we reconstituted
Rag
−/−
mice with either CD4
+
or CD8
+
T cells. Both T cell subsets increased
Rag1
−/−
mouse survival during infection, with mice that received CD8
+
T cells developing colonic ulcers but not goblet cell depletion. In contrast, mice that received CD4
+
T cells showed goblet cell depletion in concert with exaggerated IEC proliferation. To define the possible involvement of T cell-derived cytokines, we infected gamma interferon receptor gene knockout (
IFN-γR
−/−
) mice and wild-type mice given interleukin 17A (IL-17A) neutralizing antibodies and found that IFN-γ signaling was required for both goblet cell depletion and increased IEC proliferation. Immunostaining revealed that
C. rodentium
cells preferentially localized to nonhyperplastic crypts containing numerous goblet cells, whereas hyperplastic, goblet cell-depleted crypts appeared protected from infection. To address whether goblet cell depletion benefits the
C. rodentium
-infected host, we increased goblet cell numbers using the γ-secretase inhibitor dibenzazepine (DBZ), which resulted in greatly increased pathogen burdens and mortality rates. These results demonstrate that goblet cell depletion reflects host immunomodulation of IEC homeostasis and reflects a novel host defense mechanism against mucosal-adherent pathogens.
Epidemiology, management and outcome of paracetamol poisoning in an inner city emergency department
Authors: Carroll R , Benger J , Bramley K , Williams S , Griffin L , Potokar J , Gunnell D 
Published: October 2013

BackgroundParacetamol poisoning accounts for just under half of all self-poisoning cases that present to hospitals in England. Treatment with acetylcysteine is routine, yet recommendations regarding its use vary internationally and have recently been revised in England and Wales.MethodsData on all cases of paracetamol poisoning presenting to an adult inner city emergency department between May 2011 and April 2012 were prospectively collected using the Bristol Self-harm Surveillance Register.ResultsParacetamol overdoses accounted for 44% of adult self-poisoning cases. A quarter (26.9%) of patients required treatment with acetylcysteine and it was estimated that recent changes in treatment guidelines would increase that proportion to 32.6%. Paracetamol concentration was positively associated with the risk of any adverse reaction to acetylcysteine. 22.5% of patients experienced anaphylactoid reactions to acetylcysteine. There was no clear evidence of an association between risk of anaphylactoid reaction and blood paracetamol levels. Patients presenting with blood paracetamol levels greater than 200 mg/L at 4 h post-ingestion were at greater risk of repeat self-harm (HR 2.17, 95% CI 1.11 to 4.21, p=0.033).DiscussionThe recent changes in UK treatment guidelines are expected to increase the proportion of our population requiring acetylcysteine by 5.7%. We found no clear evidence that risk of anaphylactoid or more general adverse reaction to acetylcysteine was increased in patients presenting with lower blood paracetamol concentrations. Blood paracetamol level was highlighted as a potentially useful clinical indicator for risk of repeat self-harm.
The association between prehospital care and in-hospital treatment decisions in acute stroke: a cohort study
Authors: Sheppard James P , Mellor Ruth M , Greenfield Sheila , Mant Jonathan , Quinn Tom , Sandler David , Sims Don , Singh Satinder , Ward Matthew , McManus Richard J 
Published: October 2013

BackgroundHospital prealerting in acute stroke improves the timeliness of subsequent treatment, but little is known about the impact of prehospital assessments on in-hospital care.ObjectiveExamine the association between prehospital assessments and notification by emergency medical service staff on the subsequent acute stroke care pathway.MethodsThis was a cohort study of linked patient medical records. Consenting patients with a diagnosis of stroke were recruited from two urban hospitals. Data from patient medical records were extracted and entered into a Cox regression analysis to investigate the association between time to CT request and recording of onset time, stroke recognition (using the Face Arm Speech Test (FAST)) and sending of a prealert message.Results151 patients (aged 71±15 years) travelled to hospital via ambulance and were eligible for this analysis. Time of symptom onset was recorded in 61 (40%) cases, the FAST test was positive in 114 (75%) and a prealert message was sent in 65 (44%). Following adjustment for confounding, patients who had time of onset recorded (HR 0.73, 95% CI 0.52 to 1.03), were FAST-positive (HR 0.54, 95% CI 0.37 to 0.80) or were prealerted (HR 0.26, 95% CI 0.18 to 0.38), were more likely to receive a timely CT request in hospital.ConclusionsThis study highlights the importance of hospital prealerting, accurate stroke recognition, and recording of onset time. Those not recognised with stroke in a prehospital setting appear to be excluded from the possibility of rapid treatment in hospital, even before they have been seen by a specialist.
The impact of thunderstorm asthma on emergency department attendances across London during July 2013
Authors: Elliot A J , Hughes H E , Hughes T C , Locker T E , Brown R , Sarran C , Clewlow Y , Murray V , Bone A , Catchpole M , McCloskey B , Smith G E 
Published: October 2013

BackgroundThis study illustrates the potential of using emergency department attendance data, routinely accessed as part of a national syndromic surveillance system, to monitor the impact of thunderstorm asthma.MethodsThe Emergency Department Syndromic Surveillance System (EDSSS) routinely monitors anonymised attendance data on a daily basis across a sentinel network of 35 emergency departments. Attendance data for asthma, wheeze and difficulty breathing are analysed on a daily basis.ResultsA statistically significant spike in asthma attendances in two EDSSS emergency departments in London was detected on 23 July 2013, coinciding with a series of large violent thunderstorms across southern England. There was also an increase in the reported severity of these attendances.ConclusionsThis preliminary report illustrates the potential of the EDSSS to monitor the impact of thunderstorms on emergency department asthma attendances. Further work will focus on how this system can be used to quantify the impact on emergency departments, thus potentially improving resource planning and also adding to the thunderstorm asthma evidence-base.
Socioeconomic and behavioural risk factors for adverse winter health and social outcomes in economically developed countries: a systematic review of quantitative observational studies
Authors: Tanner Louise M , Moffatt Suzanne , Milne Eugene M G , Mills Susanna D H , White Martin 
Published: October 2013

BackgroundMortality and morbidity rates are often highest during the winter period, particularly in countries with milder climates. A growing body of research has identified potential socioeconomic, housing and behavioural mediators of cold weather-related adverse health and social outcomes, but an inclusive systematic review of this literature has yet to be performed.MethodsA systematic review, with narrative synthesis, of observational research published in English between 2001 and 2011, which quantified associations between socioeconomic, housing or behavioural factors and cold weather-related adverse health or social outcomes.ResultsThirty-three studies met the inclusion criteria. Average study quality was not high. Most studies failed to control for all relevant confounding factors, or to conduct research over a long enough period to ascertain causality. Low income, housing conditions and composite fuel poverty measures were most consistently associated with cold weather-related adverse health or social outcomes.ConclusionsThis review identified socioeconomic, housing and behavioural factors associated with a range of cold weather-related adverse health or social outcomes. Only tentative conclusions can be drawn due to the limitations of existing research. More robust studies are needed to address the methodological issues identified and uncover causal associations. A review of qualitative and intervention studies would help to inform policies to reduce the adverse health and social impacts of cold weather.
Isotope geochemistry (O, H and Sr) of Late Cretaceous volcanic rocks, Haţeg Basin, South Carpathians, Romania
Authors: Bojar Ana-Voica , Dodd Justin , Seghedi Ioan 
Published: October 2013

Abstract

Oxygen and strontium isotopic ratios belonging to Late Cretaceous volcaniclastic deposits of the Haţeg Basin, South Carpathians, are documented here for the first time. The analyses performed on mineral concentrates suggest that associated magmas account for an assimilation–fractional crystallization trend with
87
Sr/
86
Sr ratios of between 0.705 and 0.706, and a large range of δ
18
O up to 16‰, and a trend with higher
87
Sr/
86
Sr ratios (0.707–0.708) but lower δ
18
O (8.2–7.9‰) values for leucrocratic minerals, such as plagioclase and sanidine. The Sr–O modelling of the main trend, using mafic minerals (pyroxene and amphibole), indicate 1–3% source contamination associated with up to 20% crustal assimilation. Hydrogen isotopic composition of amphiboles, biotite and groundmass do not confirm any significant involvement of an external fluid, either hydrothermal or diagenetic.
The Cretaceous–Paleogene boundary in the East Carpathians, Romania: evidence from geochemistry, mineralogy and calcareous nannofossils
Authors: Bojar Ana-Voica , Bojar Hans-Peter 
Published: October 2013

Abstract

We performed detailed geochemical, mineralogical and calcareous nannofossils investigations on two Maastrichtian–Paleocene sections situated in the Eastern Carpathians, Romania. One of the sections is situated in the Carpathian bend area, in the Ialomiţa Valley and is composed of red marine hemipelagic sediments. The other section is located in the northern region of the Eastern Carpathians, along Varniţa Brook and consists mainly of turbidites. In both sections, the Cretaceous–Paleogene (K–Pg) boundary is characterized by nannoplankton mass extinction (over 90%) of the Cretaceous nannofloras, followed by blooms of survivor taxa, such as the calcareous dinoflagellate genus
Thoracosphaera
and the nannofloral species
Braarudosphaera bigelowii
. In the Ialomiţa section, the K–Pg boundary is marked by a drop in calcite and TOC content, as well as a negative excursion in the δ
13
C values of organic material. These trends are only partly present in the Varniţa Brook section, where both calcite and TOC content show a decrease, but no negative excursion is seen in the δ
13
C values of organic material.
Novel Mechanism of Tumor Suppression by Polarity Gene Discs Large 1 (DLG1) Revealed in a Murine Model of Pediatric B-ALL
Authors: Sandoval Gabriel J. , Graham Daniel B. , Gmyrek Grzegorz B. , Akilesh Holly M. , Fujikawa Keiko , Sammut Benedicte , Bhattacharya Deepta , Srivatsan Shuba , Kim Alfred , Shaw Andrey S. , Yang-Iott Katherine , Bassing Craig H. , Duncavage Eric , Xavier Ramnik J. , Swat Wojciech 
Published: October 2013

Abstract
Drosophila melanogaster discs large (dlg) is an essential tumor suppressor gene (TSG) controlling epithelial cell growth and polarity of the fly imaginal discs in pupal development. A mammalian ortholog, Dlg1, is involved in embryonic urogenital morphogenesis, postsynaptic densities in neurons, and immune synapses in lymphocytes. However, a potential role for Dlg1 as a mammalian TSG is unknown. Here, we present evidence that loss of Dlg1 confers strong predisposition to the development of malignancies in a murine model of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Using mice with conditionally deleted Dlg1 alleles, we identify a novel “pre-leukemic” stage of developmentally arrested early B-lineage cells marked by preeminent c-Myc expression. Mechanistically, we show that in B-lineage progenitors Dlg1 interacts with and stabilizes the PTEN protein, regulating its half-life and steady-state abundance. The loss of Dlg1 does not affect the level of PTEN mRNAs but results in a dramatic decrease in PTEN protein, leading to excessive phosphoinositide 3-kinase signaling and proliferation. Our data suggest a novel model of tumor suppression by a PDZ domain-containing polarity gene in hematopoietic cancers. Cancer Immunol Res; 1(6); 426–37. ©2013 AACR.
Deep Convection Triggering by Boundary Layer Thermals. Part II: Stochastic Triggering Parameterization for the LMDZ GCM
Authors: Rochetin Nicolas , Grandpeix Jean-Yves , Rio Catherine , Couvreux Fleur 
Published: October 2013

Abstract
This paper presents a stochastic triggering parameterization for deep convection and its implementation in the latest standard version of the Laboratoire de Météorologie Dynamique–Zoom (LMDZ) general circulation model: LMDZ5B. The derivation of the formulation of this parameterization and the justification, based on large-eddy simulation results, for the main hypothesis was proposed in Part I of this study.
Whereas the standard triggering formulation in LMDZ5B relies on the maximum vertical velocity within a mean bulk thermal, the new formulation presented here (i) considers a thermal size distribution instead of a bulk thermal, (ii) provides a statistical lifting energy at cloud base, (iii) proposes a three-step trigger (appearance of clouds, inhibition crossing, and exceeding of a cross-section threshold), and (iv) includes a stochastic component.
Here the complete implementation is presented, with its coupling to the thermal model used to treat shallow convection in LMDZ5B. The parameterization is tested over various cases in a single-column model framework. A sensitivity study to each parameter introduced is also carried out. The impact of the new triggering is then evaluated in the single-column version of LMDZ on several case studies and in full 3D simulations.
It is found that the new triggering (i) delays deep convection triggering, (ii) suppresses it over oceanic trade wind cumulus zones, (iii) increases the low-level cloudiness, and (iv) increases the convective variability. The scale-aware nature of this parameterization is also discussed.
Development of an Intense, Warm-Core Mesoscale Vortex Associated with the 8 May 2009 “Super Derecho” Convective Event*
Authors: Evans Clark , Weisman Morris L. , Bosart Lance F. 
Published: October 2013

Abstract
In this study, the dynamical processes contributing to warm-core meso-β-scale vortex formation associated with the 8 May 2009 “super derecho” are examined utilizing two complementary quasi-Lagrangian approaches—a circulation budget and backward trajectory analyses—applied to a fortuitous numerical simulation of the event. Warm-core meso-β-scale vortex formation occurs in a deeply moist, potentially stable environment that is conducive to the development of near-surface rotation and is somewhat atypical compared to known derecho-supporting environments.
Air parcels in the vicinity of the developing vortex primarily originate near the surface in the streamwise vorticity-rich environment, associated with the vertical wind shear of the low-level jet, immediately to the east of the eastward-moving system. Cyclonic vertical vorticity is generated along inflowing air parcels primarily by the ascent-induced tilting of streamwise vorticity and amplified primarily by ascent-induced vortex tube stretching. Descent-induced tilting of crosswise vorticity contributes to cyclonic vertical vorticity generation for the small population of air parcels in the vicinity of the developing vortex that originate to its north and west. No consistent source of preexisting vertical vorticity is present within the environment.
Cyclonic circulation on the scale of the warm-core meso-β-scale vortex increases in the lower troposphere in response to the mean vortex-scale convergence of cyclonic absolute vorticity and the local expulsion of eddy anticyclonic vertical vorticity generated within the system’s cold pool. Increased cyclonic circulation is partially offset by the system-scale tilting of horizontal vorticity associated with the low-level jet, rear-inflow jet, environmental vertical wind shear, and rotational flow of the warm-core vortex itself.
Near-Inertial Internal Wave Field in the Canada Basin from Ice-Tethered Profilers
Authors: Dosser Hayley V. , Rainville Luc , Toole John M. 
Published: October 2013

AbstractSalinity and temperature profiles from drifting ice-tethered profilers in the Beaufort gyre region of the Canada Basin are used to characterize and quantify the regional near-inertial internal wave field over one year. Vertical displacements of potential density surfaces from the surface to 750-m depth are tracked from fall 2006 to fall 2007. Because of the time resolution and irregular sampling of the ice-tethered profilers, near-inertial frequency signals are marginally resolved. Complex demodulation is used to determine variations with a time scale of several days in the amplitude and phase of waves at a specified near-inertial frequency. Characteristics and variability of the wave field over the course of the year are investigated quantitatively and related to changes in surface wind forcing and sea ice cover.
Combinational analysis of linkage and exome sequencing identifies the causative mutation in a Chinese family with congenital cataract
Authors: Jia Xueyuan , Zhang Feng , Bai Jing , Gao Linghan , Zhang Xuelong , Sun Haiming , Sun Donglin , Guan Rongwei , Sun Wenjing , Xu Lidan , Yue Zhichao , Yu Yang , Fu Songbin 
Published: October 2013

Abstract

Background
Congenital cataract is a Mendelian disorder that frequently causes blindness in infants. To date, various cataract-associated loci have been mapped; more than 30 genes have been identified by linkage analysis. However, the pathogenic loci in some affected families are still unknown, and new research strategies are needed. In this study, we used linkage-exome combinational analysis to further investigate the pedigree of a four-generation Chinese family with autosomal dominant coralliform cataract.

Methods
We combined whole exome sequencing and linkage analysis to identify the causative mutation. The exome capture and next-generation sequencing were used to sequence the protein-coding regions in the genome of the proband to identify rare mutations, which were further screened for candidate mutations in linkage regions. Candidate mutations were independently verified for co-segregation in the whole pedigree using Sanger sequencing.

Results
We identified a C to A transversion at nucleotide position c.70 in exon 2 of CRYGD, a cataract-associated gene. This mutation resulted in a threonine substitution for proline at amino acid residue 24.

Conclusions
We identified a missense P24T mutation in CRYGD that was responsible for coralliform cataract in our studied family. Our findings suggest that the combination of exome sequencing and linkage analysis is a powerful tool for identifying Mendelian disease mutations that might be missed by the classic linkage analysis strategy.
Synergistic growth inhibition by acyclic retinoid and phosphatidylinositol 3-kinase inhibitor in human hepatoma cells
Authors: Baba Atsushi , Shimizu Masahito , Ohno Tomohiko , Shirakami Yohei , Kubota Masaya , Kochi Takahiro , Terakura Daishi , Tsurumi Hisashi , Moriwaki Hisataka 
Published: October 2013

AbstractBackgroundA malfunction of RXRα due to phosphorylation is associated with liver carcinogenesis, and acyclic retinoid (ACR), which targets RXRα, can prevent the development of hepatocellular carcinoma (HCC). Activation of PI3K/Akt signaling plays a critical role in the proliferation and survival of HCC cells. The present study examined the possible combined effects of ACR and LY294002, a PI3K inhibitor, on the growth of human HCC cells.MethodsThis study examined the effects of the combination of ACR plus LY294002 on the growth of HLF human HCC cells.ResultsACR and LY294002 preferentially inhibited the growth of HLF cells in comparison with Hc normal hepatocytes. The combination of 1 μM ACR and 5 μM LY294002, in which the concentrations used are less than the IC50values of these agents, synergistically inhibited the growth of HLF, Hep3B, and Huh7 human HCC cells. These agents when administered in combination acted cooperatively to induce apoptosis in HLF cells. The phosphorylation of RXRα, Akt, and ERK proteins in HLF cells were markedly inhibited by treatment with ACR plus LY294002. Moreover, this combination also increased RXRE promoter activity and the cellular levels of RARβ and p21CIP1, while decreasing the levels of cyclin D1.ConclusionACR and LY294002 cooperatively increase the expression of RARβ, while inhibiting the phosphorylation of RXRα, and that these effects are associated with the induction of apoptosis and the inhibition of cell growth in human HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC.