bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐border Economic Activities, Human Capital and Efficiency: A Stochastic Frontier Analysis for OECD Countries
Authors: Ghosh Sucharita , Mastromarco Camilla
Published: January 2013

We study the growth effects of outward‐ori,ented econ,o,mies by using sto,chas,tic fron,tier anal,y,sis to mea,sure the effi,ciency exter,nal,i,ties of three forms of eco,n,omic cross‐bor,der activ,i,ties – inter,na,tional trade, for,eign direct invest,ment (FDI) and migra,tion – for OECD coun,tries. The study also exam,ines whether the effi,ciency of these cross‐bor,der activ,i,ties is affected by the level of human cap,i,tal in the host coun,try. We find that inter,na,tional trade and FDI are impor,tant chan,nels for improv,ing effi,ciency, as is human cap,i,tal accu,mu,la,tion, and that the positive effects of inter,na,tional trade, FDI, and migra,tion depend cru,cially on the level of accu,mu,lated human cap,i,tal. Our results show that the impact of human cap,i,tal is impor,tant for increas,ing effi,ciency via inter,na,tional trade flows and FDI flows, while immi,gra,tion into coun,tries that are richer in human cap,i,tal enhances their effi,ciency rel,a,tively more than immi,gra,tion into coun,tries with lower human cap,i,tal. These results remain robust to alter,nate mea,sures of human cap,i,tal, con,trols on edu,ca,tion lev,els among immi,grants, and to a non‐para,met,ric esti,ma,tion of the model.
Corneal collagen cross‐linking (CXL) for the treatment of melting keratitis in cats and dogs: a pilot study
Authors: Spiess Bernhard M. , Pot Simon A. , Florin Marion , Hafezi Farhad
Published: January 2013

Objective

UV‐A/riboflavin cross‐linking (CXL) of corneal collagen fibers is an established, highly promising therapy for corneal melting in physician‐based ophthalmology. A prospective pilot study was conducted to demonstrate proof of principle of this novel method for the treatment of melting corneal ulcers in dogs and cats.

Procedures

After obtaining owner consent,CXLwas performed in three cats and three dogs with corneal melting, which either affected the entire corneal surface or was resistant to conventional antibiotic and anticollagenolytic therapy, and affected parts or all of the corneal surface. Medical therapy was continued in all patients. The available follow‐up ranged from 2 to 22.5 months and involved slit‐lamp examination, fluorescein staining, and photographic documentation during all rechecks.

Results

Surgical stabilization of the cornea was not necessary in any case, because progression of corneal melting was arrested in all cases within 1–20 days ofCXLtreatment. Corneal re‐epithelization occurred within 7–40 days in all eyes. At 40 days afterCXL, all eyes presented a quiescent corneal state without signs of active inflammation and with beginning scar formation. The complications observed in three of the six animals included a corneal sequestrum, superficial corneal stromal pigmentation, and bullous keratopathy.

Conclusions

This study shows the feasibility ofCXLto treat progressive corneal melting in veterinary patients.CXLmay represent a cost‐efficient and safe alternative therapy in the treatment for corneal melting in veterinary ophthalmology. More investigations comparing the effectivity and complication rate ofCXLto those of standard medical treatment are necessary.
Assessment of the use of spectral domain optical coherence tomography (SD‐OCT) for evaluation of the healthy and pathological cornea in dogs and cats
Authors: Famose Frank
Published: January 2013

Purpose

Morphologic evaluation of the cornea is based on the slit‐lamp examination. In human ophthalmology, optical coherence tomography (OCT) has opened a new field in the clinical approach to anterior segment disorders and more specifically the cornea. The aim of our study is to describe spectral domainOCTexamination of the cornea in dogs and cats in clinical practice conditions.

Material and methods

One hundred eyes were examined from 52 dogs and 41 cats presented to a private practice referral center with an Optovue iVue SD‐OCT device. Sixteen healthy animals were used as control group, and the others were examined for various corneal conditions. All animals were examined after sedation or anesthesia.

Results

Normal and pathological aspects of canine and feline cornea were described for various conditions such as corneal ulcers, microbial keratitis, corneal sequestrum, infiltrations, foreign bodies, corneal dystrophies, and surgical conditions.

Conclusion

SD‐OCTexamination of normal and pathological corneal conditions in dogs and cats gave an accurate evaluation of each component of the cornea. The advantage of the technique is thein vivo, real‐time evaluation of all corneal layers with the absence of corneal contact. Constraints included the necessity of sedation for precise focus and the low quality of images obtained with too pigmented or thickened corneas.
The essential role of peripheral respiratory chemoreceptor inputs in maintaining breathing revealed when CO2 stimulation of central chemoreceptors is diminished
Authors: Fiamma Marie‐Noëlle , O’Connor Edward T. , Roy Arijit , Zuna Ines , Wilson Richard J. A.
Published: January 2013

Key points

Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep, which can have many serous health implications.

Each ventilatory overshoot following an apnoea attenuates peripheral chemoreceptor input which, in turn, has the potential to cause a further apnoea.

In a decerebrate, vagotomized, in situ rat preparation, we show that central apnoeas can be overcome both physiologically (with high peripheral CO2) and pharmacologically (with peripheral pituitary adenylate cyclase‐activating peptide).

We also show that the central apnoeic threshold, i.e. the CO2 level at which the animal stops breathing, can be lowered by increasing peripheral chemoreceptor stimulation.

These data suggest that stimulation of peripheral chemoreceptors may prevent central apnoeas, re‐affirming the peripheral chemoreceptors as possible therapeutic targets for some sleep apnea phenotypes.

Abstract  Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep. Studies in sleeping dogs suggest that withdrawal of peripheral chemoreceptor (carotid body) activation following transient ventilatory overshoots plays an essential role in causing apnoea, raising the possibility that sustaining carotid body activity during ventilatory overshoots may prevent apnoea. To test whether sustained peripheral chemoreceptor activation is sufficient to drive breathing, even in the absence of central chemoreceptor stimulation and vagal feedback, we used a vagotomized, decerebrate dual‐perfused in situ rat preparation in which the central and peripheral chemoreceptors are independently and artificially perfused with gas‐equilibrated medium. At varying levels of carotid body stimulation (CB PO2/PCO2: 40/60, 100/40, 200/15, 500/15 Torr), we decreased the brainstem perfusate PCO2 in 5 Torr steps while recording phrenic nerve activity to determine the central apnoeic thresholds. The central apnoeic thresholds decreased with increased carotid body stimulation. When the carotid bodies were strongly stimulated (CB 40/60), the apnoeic threshold was 3.6 ± 1.4 Torr PCO2 (mean ± SEM, n = 7). Stimulating carotid body afferent activity with either hypercapnia (60 Torr PCO2) or the neuropeptide pituitary adenylate cyclase‐activating peptide restored phrenic activity during central apnoea. We conclude that peripheral stimulation shifts the central apnoeic threshold to very hypocapnic levels that would likely increase the CO2 reserve and have a protective effect on breathing. These data demonstrate that peripheral respiratory chemoreceptors are sufficient to stave off central apnoeas when the brainstem is perfused with low to no CO2.
Gastrin‐releasing peptide acts via postsynaptic BB2 receptors to modulate inward rectifier K+ and TRPV1‐like conductances in rat paraventricular thalamic neurons
Authors: Hermes M. L. H. J. , Kolaj M. , Coderre E. M. , Renaud L. P.
Published: January 2013

Key points

Gastrin‐releasing peptide (GRP) is a mammalian bombesin‐like peptide that is widely distributed in the CNS. Whereas GRP is known to have a predominant excitatory action on neurons, details of the underlying membrane mechanism remain largely undefined.

We investigated GRP‐affected receptors and ionic conductances in the midline paraventricular thalamic nucleus, a brain region densely innervated by GRP‐like immunoreactive fibres.

Perforated patch clamp recording in acute brain slices showed that exposure of paraventricular thalamic nucleus neurons to low nanomolar concentrations of GRP resulted in membrane depolarization with rhythmic burst or tonic firing. These responses were due to a postsynaptic bombesin type 2 receptor‐mediated simultaneous suppression of a Ba2+‐sensitive inward rectifier K+ conductance and activation of a non‐selective cation conductance with transient receptor potential vanilloid 1‐like properties.

The data provide details on the nature of the receptor and ionic conductances involved in GRP's excitatory influence on midline thalamic neurons.

Abstract  Gastrin‐releasing peptide (GRP) is a bombesin‐like peptide with a widespread distribution in mammalian CNS, where it has a role in food intake, circadian rhythm generation, fear memory, itch sensation and sexual behaviour. While it has been established that GRP predominantly excites neurons, details of the membrane mechanism involved in this action remain largely undefined. We used perforated patch clamp recording in acute brain slice preparations to investigate GRP‐affected receptors and ionic conductances in neurons of the rat paraventricular thalamic nucleus (PVT). PVT is a component of the midline and intralaminar thalamus that participates in arousal, motivational drives and stress responses, and exhibits a prominence of GRP‐like immunoreactive fibres. Exposure of PVT neurons to low nanomolar concentrations of GRP induced sustained TTX‐resistant membrane depolarizations that could trigger rhythmic burst discharges or tonic firing. Membrane current analyses in voltage clamp revealed an underlying postsynaptic bombesin type 2 receptor‐mediated inward current that resulted from the simultaneous suppression of a Ba2+‐sensitive inward rectifier K+ conductance and activation of a non‐selective cation conductance with biophysical and pharmacological properties reminiscent of transient receptor potential vanilloid (TRPV) 1. A role for a TRPV1‐like conductance was further implied by a significant suppressant influence of a TRPV1 antagonist on GRP‐induced membrane depolarization and rhythmic burst or tonic firing. The results provide a detailed picture of the receptor and ionic conductances that are involved in GRP's excitatory action in midline thalamus.
Specimen-Specific Computational Models of Ankle Sprains Produced in a Laboratory Setting
Authors: Button Keith D. , Wei Feng , Meyer Eric G. , Haut Roger C.
Published: January 2013

The use of computational modeling to predict injury mechanisms and severity has recently been investigated, but few models report failure level ligament strains. The hypothesis of the study was that models built off neutral ankle experimental studies would generate the highest ligament strain at failure in the anterior deltoid ligament, comprised of the anterior tibiotalar ligament (ATiTL) and tibionavicular ligament (TiNL). For models built off everted ankle experimental studies the highest strain at failure would be developed in the anterior tibiofibular ligament (ATiFL). An additional objective of the study was to show that in these computational models ligament strain would be lower when modeling a partial versus complete ligament rupture experiment. To simulate a prior cadaver study in which six pairs of cadaver ankles underwent external rotation until gross failure, six specimen-specific models were built based on computed tomography (CT) scans from each specimen. The models were initially positioned with 20 deg dorsiflexion and either everted 20 deg or maintained at neutral to simulate the cadaver experiments. Then each model underwent dynamic external rotation up to the maximum angle at failure in the experiments, at which point the peak strains in the ligaments were calculated. Neutral ankle models predicted the average of highest strain in the ATiTL (29.1 ± 5.3%), correlating with the medial ankle sprains in the neutral cadaver experiments. Everted ankle models predicted the average of highest strain in the ATiFL (31.2 ± 4.3%) correlating with the high ankle sprains documented in everted experiments. Strains predicted for ligaments that suffered gross injuries were significantly higher than the strains in ligaments suffering only a partial tear. The correlation between strain and ligament damage demonstrates the potential for modeling to provide important information for the study of injury mechanisms and for aiding in treatment procedure.
Vemurafenib Potently Induces Endoplasmic Reticulum Stress–Mediated Apoptosis in BRAFV600E Melanoma Cells
Authors: Beck Daniela , Niessner Heike , Smalley Keiran S. M. , Flaherty Keith , Paraiso Kim H. T. , Busch Christian , Sinnberg Tobias , Vasseur Sophie , Iovanna Juan Lucio , Drießen Stefan , Stork Björn , Wesselborg Sebastian , Schaller Martin , Biedermann Tilo , Bauer Jürgen , Lasithiotakis Konstantinos , Weide Benjamin , Eberle Jürgen , Schittek Birgit , Schadendorf Dirk , Garbe Claus , Kulms Dagmar , Meier Friedegund
Published: January 2013

Drug resistance in melanomas may be overcome by therapies that trigger endoplasmic reticulum stress.
Embed Dynamic Content in Your Poster
Authors: Hutchins B. Ian
Published: January 2013

QR codes can be used to display dynamic data at scientific meetings.
Golgi Fragmentation in Hyperactive Neurons
Authors: Gough Nancy R.
Published: January 2013

Cultured neurons exhibit reversible Golgi fragmentation.
Chimeric Beta-Defensin Analogs, Including the Novel 3NI Analog, Display Salt-Resistant Antimicrobial Activity and Lack Toxicity in Human Epithelial Cell Lines
Authors: Scudiero Olga , Galdiero Stefania , Nigro Ersilia , Del Vecchio Luigi , Di Noto Rosa , Cantisani Marco , Colavita Irene , Galdiero Massimiliano , Cassiman Jean-Jacques , Daniele Aurora , Pedone Carlo , Salvatore Francesco
Published: January 2013

Human beta-defensins (hBDs) are crucial peptides for the innate immune response and are thus prime candidates as therapeutic agents directed against infective diseases. Based on the properties of wild-type hBD1 and hBD3 and of previously synthesized analogs (1C, 3I, and 3N), we have designed a new analog, 3NI, and investigated its potential as an antimicrobial drug. Specifically, we evaluated the antimicrobial activities of 3NI versus those of hBD1, hBD3, 1C, 3I, and 3N. Our results show that 3NI exerted greater antibacterial activity against
Pseudomonas aeruginosa
,
Escherichia coli
, and
Enterococcus faecalis
than did hBD1 and hBD3, even with elevated salt concentrations. Moreover, its antiviral activity against herpes simplex virus 1 was greater than that of hBD1 and similar to that of hBD3. Subsequently, we investigated the cytotoxic effects of all peptides in three human epithelial carcinoma cell lines: A549 from lung, CaCo-2 from colon, and Capan-1 from pancreas. None of the analogs significantly reduced cell viability versus wild-type hBD1 and hBD3. They did not induce genotoxicity or cause an increase in the number of apoptotic cells. Using confocal microscopy, we also investigated the localization of the peptides during their incubation with epithelial cells and found that they were distributed on the cell surface, from which they were internalized. Finally, we show that hBD1 and hBD3 are characterized by high resistance to serum degradation. In conclusion, the new analog 3NI seems to be a promising anti-infective agent, particularly given its high salt resistance—a feature that is relevant in diseases such as cystic fibrosis.
Pharmacodynamic Variability beyond That Explained by MICs
Authors: Soon Rachel L. , Ly Neang S. , Rao Gauri , Wollenberg Lance , Yang Kuo , Tsuji Brian , Forrest Alan
Published: January 2013

Monte Carlo simulations (MCS) present a powerful tool to evaluate candidate regimens by determining the probability of target attainment. Although these assessments have traditionally incorporated variability in pharmacokinetic (PK) parameters and MICs, consideration of interstrain pharmacodynamic (PD) variability has been neglected. A population PK/PD model was developed for doripenem using murine thigh infection data based on 20 bacterial strains. PK data were fit to a linear two-compartment model with first-order input and elimination processes and an absorption lag time from a separate site (
r
2
> 0.96). PK parameters were utilized to simulate free-drug profiles for various regimens in PD studies, from which the percentage of the dosing interval for which free-drug concentrations exceed the MIC of the targeted strain (%
f
T>MIC) was calculated. Doripenem PD was excellently described with Hill-type models (
r
2
> 0.98); significant differences between mean PD estimates determined using a two-stage approach versus population analyses were not observed (
P
> 0.05); however, the variance in 50% effective concentration (EC
50
) and maximum effect (
E
max
) among strains was much greater using the two-stage approach. Even using the population approach, interstrain variability in EC
50
(coefficient of variation expressed as a percentage [CV%] = 29.2%) and
H
(CV% = 46.1%) parameters was substantive, while the variability in
E
max
(CV% = 19.7%) was modest. This resulted in extensive variability in the range of %
fT
>MIC targets associated with stasis to those associated with a 2-log
10
reduction in bacterial burden (CV% ∼ 50%). It appears that MCS, based on the assumption that PD variability is due to MIC alone, underestimates variability and may consequently underestimate treatment failures.
Impact of Antibiotic Use on Carbapenem Resistance in Pseudomonas aeruginosa: Is There a Role for Antibiotic Diversity?
Authors: Plüss-Suard C. , Pannatier A. , Kronenberg A. , Mühlemann K. , Zanetti G.
Published: January 2013

In this study, we aimed to evaluate the relationship between the rates of resistance of
Pseudomonas aeruginosa
to carbapenems and the levels and diversity of antibiotic consumption. Data were retrospectively collected from 20 acute care hospitals across 3 regions of Switzerland between 2006 and 2010. The main outcome of the present study was the rate of resistance to carbapenems among
P. aeruginosa
. Putative predictors included the total antibiotic consumption and carbapenem consumption in defined daily doses per 100 bed days, the proportion of very broad-spectrum antibiotics used, and the Peterson index. The present study confirmed a correlation between carbapenem use and carbapenem resistance rates at the hospital and regional levels. The impact of diversifying the range of antibiotics used against
P. aeruginosa
resistance was suggested by (i) a positive correlation in multivariate analysis between the above-mentioned resistance and the proportion of consumed antibiotics having a very broad spectrum of activity (coefficient = 1.77; 95% confidence interval, 0.58 to 2.96;
P
< 0.01) and (ii) a negative correlation between the resistance and diversity of antibiotic use as measured by the Peterson homogeneity index (coefficient = −0.52;
P
< 0.05). We conclude that promoting heterogeneity plus parsimony in the use of antibiotics appears to be a valuable strategy for minimizing the spread of carbapenem resistance in
P. aeruginosa
in hospitals.
In Vitro
Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes
Authors: Hao Mingming , Jia Dandan , Li Qing , He Yongshu , Yuan Lili , Xu Shuhui , Chen Kexuan , Wu Jia , Shen Lijuan , Sun Lin , Zhao Hongbin , Yang Zhaoqing , Cui Liwang
Published: January 2013

The recent reports of resistance in
Plasmodium falciparum
to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the
in vitro
susceptibility of 63
P. falciparum
field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC
50
) of 252.7 nM and a range of 51.9 to 1,052.0 nM. In comparison, these parasites had a geometric mean IC
50
of 28.4 nM for PPQ, with a fairly wide range of 5.3 to 132.0 nM, suggesting that certain parasite isolates displayed relatively high levels of resistance to PPQ. Interestingly, within the 4 years of study, the parasites exhibited a continuous decline in susceptibilities to both CQ and PPQ, and there was a significant correlation between responses to CQ and PPQ (Pearson correlation coefficient = 0.79,
P
< 0.0001). Consistent with the CQ-resistant phenotype, all parasites carried the
pfcrt
K76T mutation, and most parasites had the CVIET type that is prevalent in Southeast Asia. In contrast,
pfmdr1
mutations were relatively rare, and no gene amplification was detected. Only the
pfmdr1
N1042D mutation was associated with resistance to CQ. For the
pfmrp1
gene, four substitutions reached relatively high prevalence of >22%, and the I876V mutation was associated with reduced sensitivity to CQ. However, we could not establish a link between PPQ responses and the polymorphisms in the three genes associated with quinoline drug resistance.
CD11a Regulates Effector CD8 T Cell Differentiation and Central Memory Development in Response to Infection with Listeria monocytogenes
Authors: Bose Tina O. , Pham Quynh-Mai , Jellison Evan R. , Mouries Juliette , Ballantyne Christie M. , Lefrançois Leo
Published: January 2013

β2 (CD18) integrins with α-chains CD11a, -b, -c, and -d are important adhesion molecules necessary for leukocyte migration and cellular interactions. CD18 deficiency leads to recurrent bacterial infections and poor wound healing due to reduced migration of leukocytes to inflammatory sites. CD8 T cells also upregulate CD11a, CD11b, and CD11c upon activation. However, the role these molecules play for CD8 T cellsin vivois not known. To determine the function of individual β2 integrins, we examined CD8 T cell responses toListeria monocytogenesinfection in CD11a-, CD11b-, and CD11c-deficient mice. The absence of CD11b or CD11c had no effect on the generation of antigen-specific CD8 T cells. In contrast, the magnitude of the primary CD8 T cell response in CD11a-deficient mice was significantly reduced. Moreover, the response in CD11a−/−mice exhibited reduced differentiation of short-lived effector cells (KLRG1hiCD127lo), although cytokine and granzyme B production levels were unaffected. Notably, CD11a deficiency resulted in greatly enhanced generation of CD62L+central memory cells. Surprisingly, CD8 T cells lacking CD11a mounted a robust secondary response to infection. Taken together, these findings demonstrated that CD11a expression contributes to expansion and differentiation of primary CD8 T cells but may be dispensable for secondary responses to infection.
The Surface Layer of Tannerella forsythia Contributes to Serum Resistance and Oral Bacterial Coaggregation
Authors: Shimotahira Naohiro , Oogai Yuichi , Kawada-Matsuo Miki , Yamada Sakuo , Fukutsuji Kenji , Nagano Keiji , Yoshimura Fuminobu , Noguchi Kazuyuki , Komatsuzawa Hitoshi
Published: January 2013

Tannerella forsythia
is an anaerobic, Gram-negative bacterium involved in the so-called “red complex,” which is associated with severe and chronic periodontitis. The surface layer (S-layer) of
T. forsythia
is composed of cell surface glycoproteins, such as TfsA and TfsB, and is known to play a role in adhesion/invasion and suppression of proinflammatory cytokine expression. Here we investigated the association of this S-layer with serum resistance and coaggregation with other oral bacteria. The growth of the S-layer-deficient mutant in a bacterial medium containing more than 20% non-heat-inactivated calf serum (CS) or more than 40% non-heat-inactivated human serum was significantly suppressed relative to that of the wild type (WT). Next, we used confocal microscopy to perform quantitative analysis on the effect of serum. The survival ratio of the mutant exposed to 100% non-heat-inactivated CS (76% survival) was significantly lower than that of the WT (97% survival). Furthermore, significant C3b deposition was observed in the mutant but not in the WT. In a coaggregation assay, the mutant showed reduced coaggregation with
Streptococcus sanguinis
,
Streptococcus salivarius
, and
Porphyromonas gingivalis
but strong coaggregation with
Fusobacterium nucleatum
. These results indicated that the S-layer of
T. forsythia
plays multiple roles in virulence and may be associated with periodontitis.
The Type VI Secretion System Encoded in Salmonella Pathogenicity Island 19 Is Required for Salmonella enterica Serotype Gallinarum Survival within Infected Macrophages
Authors: Blondel Carlos J. , Jiménez Juan C. , Leiva Lorenzo E. , Álvarez Sergio A. , Pinto Bernardo I. , Contreras Francisca , Pezoa David , Santiviago Carlos A. , Contreras Inés
Published: January 2013

Salmonella enterica
serotype Gallinarum is the causative agent of fowl typhoid, a disease characterized by high morbidity and mortality that causes major economic losses in poultry production. We have reported that
S
. Gallinarum harbors a type VI secretion system (T6SS) encoded in
Salmonella
pathogenicity island 19 (SPI-19) that is required for efficient colonization of chicks. In the present study, we aimed to characterize the SPI-19 T6SS functionality and to investigate the mechanisms behind the phenotypes previously observed
in vivo
. Expression analyses revealed that SPI-19 T6SS core components are expressed and produced under
in vitro
bacterial growth conditions. However, secretion of the structural/secreted components Hcp1, Hcp2, and VgrG to the culture medium could not be determined, suggesting that additional signals are required for T6SS-dependent secretion of these proteins.
In vitro
bacterial competition assays failed to demonstrate a role for SPI-19 T6SS in interbacterial killing. In contrast, cell culture experiments with murine and avian macrophages (RAW264.7 and HD11, respectively) revealed production of a green fluorescent protein-tagged version of VgrG soon after
Salmonella
uptake. Furthermore, infection of RAW264.7 and HD11 macrophages with deletion mutants of SPI-19 or strains with genes encoding specific T6SS core components (
clpV
and
vgrG
) revealed that SPI-19 T6SS contributes to
S
. Gallinarum survival within macrophages at 20 h postuptake. SPI-19 T6SS function was not linked to
Salmonella
-induced cytotoxicity or cell death of infected macrophages, as has been described for other T6SS. Our data indicate that SPI-19 T6SS corresponds to a novel tool used by
Salmonella
to survive within host cells.
Pathology and Pathophysiology of Inhalational Anthrax in a Guinea Pig Model
Authors: Savransky Vladimir , Sanford Daniel C. , Syar Emily , Austin Jamie L. , Tordoff Kevin P. , Anderson Michael S. , Stark Gregory V. , Barnewall Roy E. , Briscoe Crystal M. , Lemiale-Biérinx Laurence , Park Sukjoon , Ionin Boris , Skiadopoulos Mario H.
Published: January 2013

Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's “Animal Rule.” However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD
50
) of the
Bacillus anthracis
Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD
50
of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 10
4
spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans.
Running biomechanics in a long-term monitored recreational athlete with a history of Achilles tendon rupture
Authors: Jandacka Daniel , Zahradnik David , Foldyna Karel , Hamill Joseph
Published: January 2013

This study represented a unique opportunity to understand changes in the human motion biomechanics during basic locomotion within a time interval of 4 years, when the monitored individual regained his original aerobic fitness, running performance and body mass index as prior to the injury. The participant visited the laboratory a month prior to the injury and during 4 years after the surgery. The surgery, subsequent rehabilitation and a 4-year running training programme in the studied recreational athlete did not completely eliminate the consequences of the Achilles tendon rupture. The function muscle deficit is namely manifested by a lower net plantar flexion moment and a lower net-generated ankle joint power during the take-off in the stance phase. The greater dorsal flexion in the affected ankle joint at the first contact with the ground and consequently higher peaks of ground reaction forces during running are consequences of the longer Achilles tendon in the affected lower extremity and weakened calf muscles.
Symptomatic cholecystolithiasis after cholecystectomy
Authors: van Dam Paul M E L , Alexander Shandrich M , Degreef Ellen , Salemans Jan M J I , Roumen Rudi M H
Published: January 2013

A 43-year-old woman was admitted to the gastroenterology department with colicky pain in the upper abdomen. Four years earlier, she had undergone a laparoscopic cholecystectomy because of cholecystitis. She recognised her current complaints from that previous episode. An endoscopic retrograde cholangiopancreatography showed a cavity with a diameter of 2 cm which contained multiple concrements near the liver hilus. An elective surgical exploration was performed. Near the clip of the previous cholecystectomy a bulging of the biliary tract with its own duct was visualised and resected. Histological examination of this “neo” gallbladder showed that the bulging was consistent with the formation of a reservoir secondary to bile leakage, probably caused by a small peroperative lesion of the common bile duct during the previous cholecystectomy. In conclusion, our patient presented with colicky pain caused by concrements inside a ‘neo’ gallbladder.
Platypnea orthodeoxia: a ‘laid-back’ case of dyspnoea
Authors: Ali Omair M , Agarwal Ajay , Akram Salma
Published: January 2013

A man with end-stage liver disease who presented with shortness of breath. He exhibited clinical platypnea (worsening shortness of breath on sitting up) and orthodeoxia (oxygen desaturation on sitting up). Follow-up investigations led to the diagnosis of hepatopulmonary syndrome.
Disparities in fatal and non-fatal injuries between Irish travellers and the Irish general population are similar to those of other indigenous minorities: a cross-sectional population-based comparative study
Authors: Abdalla Safa , Kelleher Cecily C , Quirke Brigid , Daly Leslie ,   on behalf of the All-Ireland traveller Health Study team
Published: January 2013

Objectives

To assess recent disparities in fatal and non-fatal injury between travellers and the general population in Ireland.

Design

A cross-sectional population-based comparative study.

Setting

Republic of Ireland.

Participants

Population census and retrospective mortality data were collected from 7042 traveller families, travellers being those identified by themselves and others as members of the traveller community. Retrospective injury incidence was estimated from a survey of a random sample of travellers in private households, aged 15 years or over (702 men and 961 women). Comparable general population data were obtained from official statistical reports, while retrospective incidence was estimated from the Survey of Lifestyle, Attitude and Nutrition 2002, a random sample of 5992 adults in private households aged 18 years or over.

Outcome measures

Potential Years of Life Lost (PYLL), Standardised Mortality Ratios (SMR), Standardised Incidence Ratios (SIR) and Case Fatality Ratios (CFR).

Results

Injury accounted for 36% of PYLL among travellers, compared with 13% in the general population. travellers were more likely to die of unintentional injury than the general population (SMR=454 (95% CI 279 to 690) in men and 460 (95% CI 177 to 905) in women), with a similar pattern for intentional injury (SMR=637 (95% CI 367 to 993) in men and 464 (95% CI 107 to 1204 in women). They had a lower incidence of unintentional injury but those aged 65 years or over were about twice as likely to report an injury. Travellers had a higher incidence of intentional injuries (SIR=181 (95% CI 116 to 269) in men and 268 (95% CI 187 to 373) in women). Injury CFR were consistently higher among travellers.

Conclusions

Irish travellers continue to bear a disproportionate burden of injury, which calls for scaling up injury prevention efforts in this group. Prevention and further research should focus on suicide, alcohol misuse and elderly injury among Irish travellers.
Extending access to specialist services: the impact of an onsite helipad and analysis of the first 100 flights
Authors: Freshwater Eleanor S , Dickinson Phillip , Crouch Robert , Deakin Charles D , Eynon C Andy
Published: January 2013

Background

In November 2011, University Hospital Southampton (UHS), now a major trauma centre, opened its onsite helipad, allowing patients to be brought to the emergency department (ED) directly by air ambulance. Prior to this, helicopters were required to land at a local playing field and the patient had to be transferred by land ambulance. This study aims to investigate the impact this change in practice has had on the flow of patients to the ED.

Methods

The authors completed a retrospective case analysis of the first 100 patients brought directly to UHS by helicopter. Data were obtained from ED notes and helicopter provider databases. Analysis was conducted on the type of incident and appropriateness of referral. Incident locations were plotted geographically.

Results

100 patients arrived at UHS ED by helicopter between 17 November 2011 and 31 March 2012. Of these, 79 were primary helicopter emergency medical service (HEMS) missions and 21 were secondary transfers from other hospitals. Of the HEMS patients, 38 were likely to have been transported to another hospital, had there not been an onsite helipad at UHS. 29 passed another suitable receiving hospital en route and therefore may have come to UHS for speciality services.

Conclusions

The provision of an onsite, 24 h helipad facility at UHS has resulted in a significant number of patients being transported to the hospital by helicopter who might otherwise have attended an alternative hospital.
Association of out-of-hospital advanced airway management with outcomes after traumatic brain injury and hemorrhagic shock in the ROC hypertonic saline trial
Authors: Wang Henry E , Brown Siobhan P , MacDonald Russell D , Dowling Shawn K , Lin Steve , Davis Daniel , Schreiber Martin A , Powell Judy , van Heest Rardi , Daya Mohamud
Published: January 2013

Objective

Prior studies suggest adverse associations between out-of-hospital advanced airway management (AAM) and patient outcomes after major trauma. This secondary analysis of data from the Resuscitation Outcomes Consortium Hypertonic Saline Trial evaluated associations between out-of-hospital AAM and outcomes in patients suffering isolated severe traumatic brain injury (TBI) or haemorrhagic shock.

Methods

This multicentre study included adults with severe TBI (GCS ≤8) or haemorrhagic shock (SBP ≤70 mm Hg, or (SBP 71–90  mm Hg and heart rate ≥108 bpm)). We compared patients receiving out-of-hospital AAM with those receiving emergency department AAM. We evaluated the associations between airway strategy and patient outcomes (28-day mortality, and 6-month poor neurologic or functional outcome) and airway strategy, adjusting for confounders. Analysis was stratified by (1) patients with isolated severe TBI and (2) patients with haemorrhagic shock with or without severe TBI.

Results

Of 2135 patients, we studied 1116 TBI and 528 shock; excluding 491 who died in the field, did not receive AAM or had missing data. In the shock cohort, out-of-hospital AAM was associated with increased 28-day mortality (adjusted OR 5.14; 95% CI 2.42 to 10.90). In TBI, out-of-hospital AAM showed a tendency towards increased 28-day mortality (adjusted OR 1.57; 95% CI 0.93 to 2.64) and 6-month poor functional outcome (1.63; 1.00 to 2.68), but these differences were not statistically significant. Out-of-hospital AAM was associated with poorer 6-month TBI neurologic outcome (1.80; 1.09 to 2.96).

Conclusions

Out-of-hospital AAM was associated with increased mortality after haemorrhagic shock. The adverse association between out-of-hospital AAM and injury outcome is most pronounced in patients with haemorrhagic shock.
The delivery of the new prehospital emergency medicine curriculum: reflections on a pilot programme in the UK
Authors: McQueen Carl , Wyse Matthew
Published: January 2013

Introduction

Pre-hospital Emergency Medicine is a subspecialty of Emergency Medicine and Anaesthesia in the UK, overseen by the Inter-collegiate Board for Training in Pre-hospital Emergency Medicine (IBTPHEM). Organisations delivering General Medical Council (GMC) approved programmes require clear educational governance frameworks to ensure high standards of training. This study outlines the experiences of an Emergency Medicine trainee during an Out of Programme Year with a regional Air Ambulance service in the UK.

Methods

Retrospective review of the clinical logbook for an Emergency Medicine trainee during a 12-month attachment with an Air Ambulance service in the UK. IBTPHEM assessment tools were completed to complement the clinical logbook. Clinical experience and the degree of clinical supervision were compared with the standards published by the IBTPHEM.

Results

Supervision rates were similar to those in other pilots (17.33%). Clinical workload was comparable with that reported in other organisations. More advanced procedures (eg, conscious sedation/prehospital anaesthetics) were completed than in IBTPHEM pilot programmes. The vast majority of curriculum elements detailed by the IBTPHEM were fulfilled.

Conclusions

The experiences of an Emergency Medicine trainee in pilot programme at a regional Air Ambulance in the UK compared favourably with the results of formal pilots of the IBTPHEM programme conducted at other centres. The IBTPHEM assessment tools are appropriately designed and sufficient in number to ensure that fulfilment of the curriculum elements can be recorded and trainee development monitored. Areas for future developments in training and support, notably in curriculum areas regarding the management of obstetric prehospital emergencies, are suggested.
Evaluation of a simple technique for recovering fish from capture stress: integrating physiology, biotelemetry, and social science to solve a conservation problem
Authors: Donaldson M.R. , Raby G.D. , Nguyen V.N. , Hinch S.G. , Patterson D.A. , Farrell A.P. , Rudd M.A. , Thompson L.A. , O'Connor C.M. , Colotelo A.H. , McConnachie S.H. , Cook K.V. , Robichaud D. , English K.K. , Cooke S.J.
Published: January 2013

We evaluate the utility of an inexpensive, portable recovery bag designed to facilitate recovery of fish from capture stress by combining physiological assays, biotelemetry, and social science surveys. Adult migrating Pacific salmon (Oncorhynchus spp.) were used as a model, since some of their populations are threatened. While catch-and-release is common, there is a need to ensure that it is sustainable. A social science survey revealed that anglers generally have positive attitudes towards recovery bag use, particularly if research identifies that such techniques could be effective. Physiological assays on pink salmon (Oncorhynchus gorbuscha) revealed benefits of both high- and low-velocity recovery, but high velocity was most effective with reduced plasma cortisol concentrations and similar plasma sodium and chloride concentrations as those found in controls at all recovery durations. A biotelemetry study on sockeye salmon (Oncorhynchus nerka) captured by anglers and stressed by air exposure then placed in recovery bags had 20% higher, but not significantly different, survival than no-recovery salmon. The integration of natural science and social science provides an important step forward in developing methods for promoting recovery of fish from capture.
Incorporating stakeholders' knowledge to stock assessment: Central Baltic herring
Authors: Mäntyniemi Samu , Haapasaari Päivi , Kuikka Sakari , Parmanne Raimo , Lehtiniemi Maiju , Kaitaranta Joni
Published: January 2013

We present a method by which the knowledge of stakeholders can be taken into account in stock assessment. The approach consists of a structured interview process followed by quantitative modelling of the answers. The outcome is a set of probability models, each describing the views of different stakeholders. Individual models are then merged to a large model by applying the techniques of Bayesian model averaging, and this model is conditioned on stock assessment data. As a result, the views of interviewed stakeholders have been taken into account and weighed based on how well their views are supported by the observed data. We applied this method to the Baltic Sea herring (Clupea harengus) stock assessment by interviewing six stakeholders and conditioning the resulting models on stock assessment data provided by the International Council for the Exploration of the Sea.
Molecular cytogenetic analysis of wheat – Elymus repens introgression lines with resistance to Fusarium head blight
Authors: Zeng J. , Cao W. , Hucl P. , Yang Y. , Xue A. , Chi D. , Fedak G.
Published: January 2013

Elymus repens (L.) Gould (2n = 6x = 42, StStStStHH) is a hexaploid perennial wheatgrass species from the tribe Triticeae, distantly related to bread wheat Triticum aestivum L. (2n = 6x = 42, AABBDD). As a potential source of resistance to Fusarium head blight (FHB), E. repens was crossed to common wheat to transfer resistance genes. The progeny were advanced to homozygosity by single seed descent. A total of eight BC1F9 progeny lines were selected and characterized in this study. The chromosome numbers of these derived lines ranged from 42 to 56, including lines with 44, 52, and 54 chromosomes. All of the lines were cytologically stable in terms of meiotic chromosome behavior. The univalent frequency in the lines varied between 0.34 and 2.36 per cell. Similarly, the multivalent frequency did not exceed 1% in any of the lines. GISH analysis revealed that the number of intact wheat chromosomes in the various lines varied between 40 and 44. Numerous translocated chromosomes were detected in all lines. The translocations involved chromosomal segments from wheat, and the St and H genomes of E. repens. Furthermore, trigenomic translocated chromosomes were detected in some of the lines. The introgression into wheat chromosomes included not only terminal types but also interstitial segments. The Fusarium head blight resistance of the eight lines, following point inoculation, varied from 5.65% infected florets to 11.46% compared with the check cultivars T. aestivum ‘Roblin’ and T. aestivum ‘Crocus’ at 100% and 85%, respectively.
NEUTRINO MASS AND THE STANDARD MODEL
Authors: KLINKHAMER F. R.
Published: January 2013

It is pointed out (not for the first time) that the minimal Standard Model, without additional gauge-singlet right-handed neutrinos or isotriplet Higgs fields, allows for nonvanishing neutrino masses and mixing. The required interaction term is non-renormalizable and violates B-L conservation. The ultimate explanation of this interaction term may or may not rely on grand unification.
ANALYTICAL MODELING OF THE EFFECTS OF ELECTROSTATIC ACTUATION AND CASIMIR FORCE ON THE PULL-IN INSTABILITY AND STATIC BEHAVIOR OF TORSIONAL NANO/MICRO ACTUATORS
Authors: MOEENFARD HAMID , DARVISHIAN ALI , AHMADIAN MOHAMMAD TAGHI
Published: January 2013

This paper studies the effect of Casimir force on the pull-in instability of electrostatically actuated torsional nano/micro actuators. Dependence of the actuator's pull-in angle and pull-in voltage on several design parameters are investigated and it is found that Casimir force can considerably reduce the stability limits of the torsional actuators. Nonlinear equilibrium equation is solved numerically and analytically using straight forward perturbation expansion method. It is observed that a fourth-order perturbation approximation can precisely model the behavior of a torsional actuator. The results of this paper can be used for safe and stable design of torsional nano/micro actuators.
Combining Formal Methods for the Development of Reactive Systems
Authors: Mosbahi Olfa
Published: January 2013

This article deals with the use of two verification approaches: theorem proving and model checking. We focus on the Event-B method by using its associated theorem proving tool (Click_n_Prove), and on the language TLA
+
by using its model checker TLC. By considering the limitation of the Event-B method to invariance properties, we propose to apply the language TLA
+
to verify liveness properties on a software behavior. We extend first the expressivity and the semantics of a B model (called
temporal B model
) to deal with the specification of fairness and eventuality properties. Second, we give transformation rules from a temporal B model into a TLA
+
module. We present in particular, our prototype system called B2TLA
+
, that we have developed to support this transformation; then we can verify these properties thanks to the model checker TLC on finite state systems. For the verification of infinite-state systems, we propose the use of the predicate diagrams. We illustrate our approach on a case study of a parcel sorting system.
Divided by division
Authors: Neville-Neil George V.
Published: January 2013

Is there a "best used by" date for software?
The value of microprocessor designs
Authors: Aizcorbe Ana , Kortum Samuel , Pillai Unni
Published: January 2013

Applying a centuries-old technique to modern cost estimation.
Rethinking passwords
Authors: Cheswick William
Published: January 2013

Our authentication system is lacking. Is improvement possible?
A decade of OS access-control extensibility
Authors: Watson Robert N. M.
Published: January 2013

Open source security foundations for mobile and embedded devices.
The explosive growth of postdocs in computer science
Authors: Jones Anita
Published: January 2013

Considering the factors influencing the recent rapid increase in the number of postdoctoral positions in computer science.