bluuebunny/crossref_metadata_2025 huggingface dataset:
Lot‐to‐lot variability in HLA antibody screening using a multiplexed bead‐based assay
Authors: Gandhi Manish J. , Carrick Danielle M. , Jenkins Sarah , De Goey Steven , Ploeger Nancy A. , Wilson Gregory A. , Lee Jar How , Winters Jeffrey L. , Stubbs James R. , Toy Pearl , Norris Philip J. ,   National Heart, Lung, and Blood Institute (NHLBI) Specialized Center of Clinically Oriented Research (SCCOR) TRALI Study and Retrovirus Epidemiology Donor Study‐II (REDS‐II)
Published: January 2013

Background

Identifying antibodies to HLA (anti‐HLA) by solid‐phase assays is used to screen blood donors to mitigate transfusion‐related acute lung injury risk. Various cutoffs for detection assays have been proposed in the literature; however, these do not take into consideration lot‐to‐lot variability of commercially available assays.

Study Design and Methods

Samples from 93 nontransfused males were tested using five different lots of a multiplex bead‐based anti‐HLA detection kit. A subset of 17 samples was tested on 5 days using a single lot. An additional 96 samples from donations with varied anti‐HLA levels were tested using kits from two different lots. Results were reported as a normalized background (NBG) ratio.

Results

For the 93 nontransfused donors, NBG values generated using the reference lot were significantly higher than those obtained with three of the four comparator lots. However, for the 96 samples with low‐, moderate‐, and higher‐level anti‐HLA, Class I (CL‐I) values were 1.4 times lower and Class II (CL‐II) values were 1.2 times lower using the reference versus comparator lot. For CL‐I antibodies the between‐lot standard deviation (SD) was 1.36 (95% confidence interval [CI], 1.19‐1.60), while the between‐day SD was 1.27 (95% CI, 1.08‐1.52). Similarly, for CL‐II antibodies the between‐lot SD was 0.81 (95% CI, 0.70‐0.95), while the between‐day SD was 0.50 (95% CI, 0.43‐0.60).

Conclusions

There is interlot variability in the tested HLA detection assay as well as significant bias between lots. It may be reasonable to develop a new cutoff when a new lot is obtained.
Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats
Authors: Sévoz‐Couche Caroline , Brouillard Charly , Camus Françoise , Laude Dominique , De Boer Sietse F. , Becker Chrystel , Benoliel Jean‐Jacques
Published: January 2013

Key points

Anxiety disorders reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). This may lead to sudden cardiac death.

To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions that lead to an anxiety‐like state.

In this model, HRV and BRS were reduced, reflex of a shift of the autonomic balance towards sympathetic predominance.

Pharmacological blockade of the dorsomedial hypothalamus (DMH) reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5‐HT3receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV.

In conclusion, repeated social defeat in the rat leads to an anxiety‐like state, in which the DMH and the NTS are chronically activated and are responsible for dysautonomia. These regions may constitute new targets against sudden cardiac death.

Abstract Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety‐like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety‐like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5‐HT3receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety‐like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders.
Quantifying the Visibility of Surface Distortions in Class “A” Automotive Exterior Body Panels
Authors: Fernholz K. D.
Published: January 2013

Visible distortions in Class “A” automotive surfaces are unacceptable to vehicle customers and therefore are considered to be cosmetic defects. The automotive industry currently relies upon subjective assessment of the severity of these distortions to determine whether a component's surface appearance is acceptable. Given the inherent variability in subjective assessments, however, an objective measurement for assessing the severity of defects would be of great benefit to the industry. The issues that need to be addressed to objectively quantify the severity of one particular type of surface distortion are discussed and a methodology for quantifying the severity of that surface distortion in a way that correlates to human perception is proposed. Experimental and finite element model data supporting the proposed methodology is presented.
A Methodology of Noncontact Automatic Measurement and Development of an Online Measurement Unit on Charge Temperature of a Large Caliber Artillery
Authors: Lu Xin , Zhou Yanhuang , Chen Jincao
Published: January 2013

Charge temperature is one of the main tactical and technical indices for a large caliber self-propelled gun, and is a critical firing datum affecting the projectile muzzle velocity and gun firing accuracy. In this paper, on the basis of analyzing the heat transfer character of propellant, an unsteady-state heat conduction model describing the variation of the charge temperature is built and the finite-difference implicit schemes are theoretically deduced using the volume equilibrium method for numerical simulation. Comparing simulation curves with experiment results indicates that the physical models used reflect the real-time change process of the charge temperature with the environment temperature. A noncontact automatic online charge temperature measurement unit is developed. This unit can accurately measure the temperature field and real-time average temperature of the charge for all charge zones placed in a combat vehicle and simultaneously transfer the temperature information to the gunner task terminal computer through a controller area network (CAN) bus interface for trajectory calculation and firing data correction, ensuring the weapon system meets the requirements of digitalization and informatization.
Modeling of Interior Ballistic Gas-Solid Flow Using a Coupled Computational Fluid Dynamics-Discrete Element Method
Authors: Cheng Cheng , Zhang Xiaobing
Published: January 2013

In conventional models for two-phase reactive flow of interior ballistic, the dynamic collision phenomenon of particles is neglected or empirically simplified. However, the particle collision between particles may play an important role in dilute two-phase flow because the distribution of particles is extremely nonuniform. The collision force may be one of the key factors to influence the particle movement. This paper presents the CFD-DEM approach for simulation of interior ballistic two-phase flow considering the dynamic collision process. The gas phase is treated as a Eulerian continuum and described by a computational fluid dynamic method (CFD). The solid phase is modeled by discrete element method (DEM) using a soft sphere approach for the particle collision dynamic. The model takes into account grain combustion, particle-particle collisions, particle-wall collisions, interphase drag and heat transfer between gas and solid phases. The continuous gas phase equations are discretized in finite volume form and solved by the AUSM+-up scheme with the higher order accurate reconstruction method. Translational and rotational motions of discrete particles are solved by explicit time integrations. The direct mapping contact detection algorithm is used. The multigrid method is applied in the void fraction calculation, the contact detection procedure, and CFD solving procedure. Several verification tests demonstrate the accuracy and reliability of this approach. The simulation of an experimental igniter device in open air shows good agreement between the model and experimental measurements. This paper has implications for improving the ability to capture the complex physics phenomena of two-phase flow during the interior ballistic cycle and to predict dynamic collision phenomena at the individual particle scale.
Experimental Study and Numerical Simulation on Propagation Properties of a Plasma Jet in a Cylindrical Liquid Chamber
Authors: Yu Yonggang , Zhang Qi , Zhao Na , Liu Dongyao
Published: January 2013

A simulator is designed to explore the interactive mechanism of a plasma jet with the liquid medium in the bulk-loaded liquid electrothermal chemical launching process. The properties of the plasma jet expanding in the liquid and the mixing characteristics of the plasma jet with liquid in the cylindrical chamber are studied using a high speed camera system. According to the experimental results, a two-dimensional axisymmetric unsteady compressible flow model has been proposed. The transient characteristics of the jet in flow field have been simulated. The results indicate that, during the expansion of the plasma jet in the liquid medium, there is relatively strong turbulent mixing. The interface between the two phases is not smooth and fluctuates with time stochastically. The higher the discharge voltage is, the stronger the Helmholtz instability effect will be. The Taylor cavity forming during the jet expansion can be divided into three regions: the main flow region, the compression region, and the backflow vortex region. In the main flow region the temperature and velocity of the plasma jet are relatively high and both decrease along the axial and radial direction. The pressure near the Taylor cavity head is high. The high pressure region grows gradually while the pressure value decreases. The calculated axial expansion displacement of the Taylor cavity coincides well with the measured one from experiment.
Left Ventricular Pressure Gating in Ovine Cardiac Studies: A Software-Based Method
Authors: Acevedo-Bolton Gabriel , Suzuki Takamaro , Malhotra Deepak , Zhang Zhihong , Wallace Arthur W. , Guccione Julius M. , Saloner David A. , Ratcliffe Mark B.
Published: January 2013

Cardiac imaging using magnetic resonance requires a gating signal in order to compensate for motion. Human patients are routinely scanned using an electrocardiogram (ECG) as a gating signal during imaging. However, we found that in sheep the ECG is not a reliable method for gating. We developed a software based method that allowed us to use the left ventricular pressure (LVP) as a reliable gating signal. By taking the time derivative of the LVP (dP/dt), we were able to start imaging at both end-diastole for systolic phase images, and end-systole for diastolic phase images. We also used MR tissue tagging to calculate 3D strain information during diastole. Using the LVP in combination with our digital circuit provided a reliable and time efficient method for ovine cardiac imaging. Unlike the ECG signal the left ventricular pressure was a clean signal and allowed for accurate, nondelay based triggering during systole and diastole.
Electrical instability in LaLuO3 based metal–oxide–semiconductor capacitors and role of the metal electrodes
Authors: Rao Rosario , Irrera Fernanda
Published: January 2013

Trapping in LaLuO3 MOS capacitors with different metal nitride gates is investigated for the first time. The instability of the flat band voltage during electrical stress is monitored systematically with the pulsed C-V technique as function of stress time and voltage. Ad-hoc experiments aiming to force electron trapping in sites close to the metal/high-k interface are performed, and the role of different metal nitride gates is discussed. Trapping exhibits a power-law dependence on stress time in any investigated condition. Interpolation of the experimental data with an analytical model of trapping allows extraction of the energy level of traps involved in the capture mechanism.
Rif1 Prevents Resection of DNA Breaks and Promotes Immunoglobulin Class Switching
Authors: Di Virgilio Michela , Callen Elsa , Yamane Arito , Zhang Wenzhu , Jankovic Mila , Gitlin Alexander D. , Feldhahn Niklas , Resch Wolfgang , Oliveira Thiago Y. , Chait Brian T. , Nussenzweig André , Casellas Rafael , Robbiani Davide F. , Nussenzweig Michel C.
Published: January 2013

Fixing Broken DNA

Some physiological processes, such as immunoglobulin class switching and telomere attrition, result in double-stranded DNA breaks. The DNA damage repair protein, 53BP1, prevents nucleolytic processing of these breaks, but the proteins it partners with to do this are unknown (see the Perspective by

Lukas and Luka
s

).

Di Virgilio
et al.

(p.
711
, published online 10 January), using mass spectroscopy–based methods, and

Zimmermann
et al.

(p.
700
, published online 10 January), using a telomere-based assay, identify Rif1 as a 53BP1 phosphorylation- and DNA damage–dependent interaction partner. Mice with a B cell–specific deletion in Rif1 showed impaired immunoglobulin class switching. Rif1-deficient cells exhibited extensive 5′-3′ resection at DNA ends, with enhanced genetic instability. Thus, Rif1 partners with 53BP1 to promote the proper repair of double-stranded DNA breaks.
53BP1 Regulates DSB Repair Using Rif1 to Control 5′ End Resection
Authors: Zimmermann Michal , Lottersberger Francisca , Buonomo Sara B. , Sfeir Agnel , de Lange Titia
Published: January 2013

Fixing Broken DNA

Some physiological processes, such as immunoglobulin class switching and telomere attrition, result in double-stranded DNA breaks. The DNA damage repair protein, 53BP1, prevents nucleolytic processing of these breaks, but the proteins it partners with to do this are unknown (see the Perspective by

Lukas and Luka
s

).

Di Virgilio
et al.

(p.
711
, published online 10 January), using mass spectroscopy–based methods, and

Zimmermann
et al.

(p.
700
, published online 10 January), using a telomere-based assay, identify Rif1 as a 53BP1 phosphorylation- and DNA damage–dependent interaction partner. Mice with a B cell–specific deletion in Rif1 showed impaired immunoglobulin class switching. Rif1-deficient cells exhibited extensive 5′-3′ resection at DNA ends, with enhanced genetic instability. Thus, Rif1 partners with 53BP1 to promote the proper repair of double-stranded DNA breaks.
The Bacteriophage T7 Virion Undergoes Extensive Structural Remodeling During Infection
Authors: Hu Bo , Margolin William , Molineux Ian J. , Liu Jun
Published: January 2013

Phage Invasion

Bacteriophages are responsible for much of bacterial evolution, both by imposing selection for resistance to infection and by horizontal gene transfer of host genes to new bacteria. However, we know surprisingly little about the initiation of phage infection.

Hu
et al.

(p.
576
, published online 10 January) used high-throughput cryo-electron tomography and sub-volume analysis to examine
Escherichia coli
minicells infected with both wild-type and mutant T7 bacteriophages. High-resolution views of phage structures at different stages of infection reveal the de novo formation of an extended tail by the ejection of internal head proteins, in order to form the channel for DNA transport into the cytoplasm.
Impact of Host Membrane Pore Formation by the Yersinia pseudotuberculosis Type III Secretion System on the Macrophage Innate Immune Response
Authors: Kwuan Laura , Adams Walter , Auerbuch Victoria
Published: January 2013

Type III secretion systems (T3SSs) are used by Gram-negative pathogens to form pores in host membranes and deliver virulence-associated effector proteins inside host cells. In pathogenic
Yersinia
, the T3SS pore-forming proteins are YopB and YopD. Mammalian cells recognize the
Yersinia
T3SS, leading to a host response that includes secretion of the inflammatory cytokine interleukin-1β (IL-1β), Toll-like receptor (TLR)-independent expression of the stress-associated transcription factor Egr1 and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), and host cell death. The known
Yersinia
T3SS effector proteins are dispensable for eliciting these responses, but YopB is essential. Three models describe how the
Yersinia
T3SS might trigger inflammation: (i) mammalian cells sense YopBD-mediated pore formation, (ii) innate immune stimuli gain access to the host cytoplasm through the YopBD pore, and/or (iii) the YopB-YopD translocon itself or its membrane insertion is proinflammatory. To test these models, we constructed a
Yersinia pseudotuberculosis
mutant expressing YopD devoid of its predicted transmembrane domain (YopD
ΔTM
) and lacking the T3SS cargo proteins YopHEMOJTN. This mutant formed pores in macrophages, but it could not mediate translocation of effector proteins inside host cells. Importantly, this mutant did not elicit rapid host cell death, IL-1β secretion, or TLR-independent Egr1 and TNF-α expression. These data suggest that YopBD-mediated translocation of unknown T3SS cargo leads to activation of host pathways influencing inflammation, cell death, and response to stress. As the YopD
ΔTM
Y. pseudotuberculosis
mutant formed somewhat smaller pores with delayed kinetics, an alternative model is that the wild-type YopB-YopD translocon is specifically sensed by host cells.
Helicobacter pylori-Induced Disruption of Monolayer Permeability and Proinflammatory Cytokine Secretion in Polarized Human Gastric Epithelial Cells
Authors: Fiorentino Maria , Ding Hua , Blanchard Thomas G. , Czinn Steven J. , Sztein Marcelo B. , Fasano Alessio
Published: January 2013

Helicobacter pylori
infection of the stomach is related to the development of diverse gastric pathologies. The ability of
H. pylori
to compromise epithelial junctional complexes and to induce proinflammatory cytokines is believed to contribute to pathogenesis. The purpose of this study was to use an
in vitro
human gastric epithelial model to investigate the ability of
H. pylori
to affect permeability and the extent and polarity of the host inflammatory response. NCI-N87 monolayers were cocultured with live or heat-killed
H. pylori
or culture supernatants. Epithelial barrier function was measured by transepithelial electric resistance (TEER) analysis, diffusion of fluorescein isothiocyanate (FITC)-labeled markers, and immunostaining for tight junction proteins. Supernatants from both apical and basolateral chambers were tested for cytokine production by multiplex analysis.
H. pylori
caused a significant decrease in TEER, an increased passage of markers through the infected monolayer, and severe disruption and mislocalization of ZO-1 and claudin-1 proteins. Cell viability was not altered by
H. pylori
, indicating that loss of barrier function could be attributed to a breakdown of tight junction integrity. Significantly high levels of cytokine secretion were induced by either viable or heat-killed
H. pylori
.
H. pylori
affects monolayer permeability of polarized human gastric epithelial cells. Proinflammatory cytokines were secreted in a polarized manner, mostly basolaterally. Live bacteria are required for disruption of tight junctions but not for the induction of cytokine secretion. The NCI-N87 cell line provides an excellent model for the
in vitro
study of
H. pylori
pathogenesis and the epithelial cell host response to infection.
Open surgical management of a ruptured intracranial aneurysm in Klippel-Trenaunay-Weber (KTW) syndrome
Authors: Smitherman Adam Derik , Woodall Michael Neil , Alleyne Cargill H , Rahimi Scott Y
Published: January 2013

A 24-year-old man with a history of Klippel-Trenaunay-Weber syndrome presented with severe headache and neck pain. Work-up revealed subarachnoid hemorrhage and evidence of multiple intracranial aneurysms. The patient was treated with open surgical clipping of his ruptured aneurysm and is currently doing well.
Anaphylaxis in pregnancy: a rare cause of neonatal mortality
Authors: Berenguer Alberto , Couto Alexandra , Brites Vera , Fernandes Rosário
Published: January 2013

Anaphylaxis is a rare condition in pregnancy. Drugs are the aetiological agents most often implicated. Maternal anaphylaxis can lead to significant fetal morbidity and even mortality if uterine perfusion and maternal oxygenation are compromised. Significant risk of neonatal neurological damage or death can occur even when the maternal clinical outcome is favourable. The authors present the case of a newborn, born at gestational age of 29 weeks, who died at 11 days of life with hypoxic–ischaemic cerebral injuries as a consequence of maternal anaphylaxis following the administration of amoxicillin in the community setting.
Thiamine and spinocerebellar ataxia type 2
Authors: Costantini Antonio , Pala Maria Immacolata , Colangeli Marco , Savelli Serena
Published: January 2013

Spinocerebellar ataxia type 2 is a genetic disorder characterised by the degeneration of the cerebellum, its connections and degeneration in brainstem areas. Some observations indicate that high doses of thiamine may lead to the partial regression of the symptoms. One patient was under rehabilitative treatment from June 2011 to July 2012. We assessed the level of fatigue using the Fatigue Severity Scale. We performed the Scale for Assessment and Rating of Ataxia and Robertson Profile for Dysarthria (Italian version). Thiamine and thiamine pyrophosphate levels in the blood were within the healthy reference range. We started a parenteral therapy with 100 mg intramuscular every 7 days. The therapy led to a partial regression of fatigue within a few days. After about 3 months, a discreet improvement of motor symptoms especially in speech was observed. The symptoms could derive from a focal thiamine deficiency that could determine a selective neuronal loss.
Immunoglobulin G4-related intracranial inflammatory pseudotumours along both the oculomotor nerves
Authors: Tomio Ryosuke , Ohira Takayuki , Wenlin Du , Yoshida Kazunari
Published: January 2013

We report the first documented case of IgG4-related inflammatory pseudotumours (IPTs) along the bilateral oculomotor nerves. A man in his 60s complained of decreased vision. He exhibited bilateral optic nerve atrophy without any extraocular movement deficits. MRI revealed enhanced masses that reached from the bilateral cavernous sinus to within the bilateral orbits. The tumours extended along the lines of the bilateral oculomotor nerves. The patient's serum level of IgG4 was high, 147 mg/dl. A biopsy specimen showed inflammatory cell-rich lesions against a collagenous stroma. Immunostaining revealed infiltration of CD138-positive plasma cells, which were mainly IgG and IgG4 positive. The IgG4/IgG ratio was greater than 0.4. These factors led us to a diagnosis of IgG4-related IPTs. Oral administration of prednisolone (30 mg/day) was started 3 months after the operation and continued for 6 months with gradual tapering. The tumour was significantly reduced by prednisolone.
Acute adrenal failure following anticoagulation with dabigatran after hip replacement and thrombolysis for massive pulmonary embolism
Authors: Best Martin , Palmer Kate , Jones Quentin Christopher , Wathen Christopher G
Published: January 2013

A 75-year-old woman presented 9 days post-total hip replacement with sudden onset of shortness of breath and fever. She had been discharged taking dabigatran. The patient was treated for sepsis with antibiotics and fluids. However, she deteriorated and was transferred to the intensive care unit. Following a 10 s asystolic episode the patient was thrombolysed with alteplase for presumed massive pulmonary embolism. Initially, her blood pressure and oxygen saturation improved. However, over the next few days, she remained persistently hypotensive. A CT scan of her chest, abdomen and pelvis demonstrated bilateral adrenal haemorrhages. A short synacthen test confirmed acute adrenal failure.
Non-syndromic multiple supernumerary teeth: a rare entity
Authors: Agrawal Jiwanasha Manish , Agrawal Manish Suresh , Nanjannawar Lalita Girish , Adaki Raghavendra Vithalappa
Published: January 2013

Hyperdontia or supernumerary teeth without associated syndromes is a rare phenomenon, as supernumerary teeth are usually associated with cleft lip and palate or other syndromes such as Gardeners syndrome, cleidocranial dysplasia, trichorhinophalangic syndrome, etc. A 15-year-old girl reported for orthodontic treatment with a chief complaint of irregular teeth and unaesthetic smile. On examination class I malocclusion with severe crowding of upper anteriors, anterior open bite of 5 mm, cross bite with upper right posteriors, upper midline shift to right by 5 mm and two supernumerary teeth placed buccally in between 16 & 17 and 26 & 27, respectively, were found. On routine radiographical examination, two additional impacted supernumerary teeth were noticed distal to 18 and in mandibular arch in between roots of 35 and 36. A general physician was consulted who confirmed that there was no associated syndrome. Family history did not reveal any positive findings.
Takayasu's arteritis presenting as digital gangrene of right hand
Authors: Verma Sudhir , Saraf Sameer , Himanshu D , Singh Shailesh
Published: January 2013

Takayasu's arteritis (TA) is a chronic inflammatory disease of medium and large vessels, mainly involving the aorta and its major branches. TA may have diverse clinical presentation including claudication, stroke, asymmetric pulse or blood pressure. However, the association of TA with digital gangrene is a rare entity. Here, we report a case of a 40-year-old woman who presented with digital gangrene of the right hand, which on workup was diagnosed as a case of TA.
If it walks like Crohn's and talks like Crohn's, it must be…
Authors: Hall Philip S J , Allen Patrick B , Diong K L , Varghese Abraham
Published: January 2013

A 30-year-old man presented with a 6- month history of nausea, vomiting and diarrhoea. This was associated with 25 kg weight loss and a right-sided abdominal colic. He had been provisionally diagnosed with Crohn's disease 6 months back and treated with budesonide and mesalazine. Investigations including C reactive protein, white cell count, coeliac antibodies, fasting gut hormones and faecal elastase were all normal. Colonoscopy and ileoscopy were normal both macroscopically and microscopically. Small bowel series and labelled white cell scan were both unremarkable. A CT scan suggested the presence of mild right-sided abdominal lymphadenopathy. Laparoscopy of entire small bowel and colon was normal. But had something been missed? An adrenocorticotrophic hormone stimulation test demonstrated inadequate cortisol response and a diagnosis of adrenal insufficiency was confirmed. Addison's disease can present with a variety of gastrointestinal symptoms and should be considered in the diagnostic work-up of these patients.
A pilot study of rapid whole-genome sequencing for the investigation of aLegionellaoutbreak
Authors: Reuter Sandra , Harrison Timothy G , Köser Claudio U , Ellington Matthew J , Smith Geoffrey P , Parkhill Julian , Peacock Sharon J , Bentley Stephen D , Török M Estée
Published: January 2013

Objectives

Epidemiological investigations of Legionnaires’ disease outbreaks rely on the rapid identification and typing of clinical and environmentalLegionellaisolates in order to identify and control the source of infection. Rapid bacterial whole-genome sequencing (WGS) is an emerging technology that has the potential to rapidly discriminate outbreak from non-outbreak isolates in a clinically relevant time frame.

Methods

We performed a pilot study to determine the feasibility of using bacterial WGS to differentiate outbreak from non-outbreak isolates collected during an outbreak of Legionnaires’ disease. SevenLegionellaisolates (three clinical and four environmental) were obtained from the reference laboratory and sequenced using the Illumina MiSeq platform at Addenbrooke's Hospital, Cambridge. Bioinformatic analysis was performed blinded to the epidemiological data at the Wellcome Trust Sanger Institute.

Results

We were able to distinguish outbreak from non-outbreak isolates using bacterial WGS, and to confirm the probable environmental source. Our analysis also highlighted constraints, which were the small number ofLegionella pneumophilaisolates available for sequencing, and the limited number of published genomes for comparison.

Conclusions

We have demonstrated the feasibility of using rapid WGS to investigate an outbreak of Legionnaires’ disease. Future work includes building larger genomic databases ofL pneumophilafrom both clinical and environmental sources, developing automated data interpretation software, and conducting a cost–benefit analysis of WGS versus current typing methods.
Spatial variation of salt intake in Britain and association with socioeconomic status
Authors: Ji Chen , Kandala Ngianga-Bakwin , Cappuccio Francesco P
Published: January 2013

Objectives

To evaluate spatial effects of variation and social determinants of salt intake in Britain.

Design

Cross-sectional survey.

Setting

Great Britain.

Participants

2105 white male and female participants, aged 19–64 years, from the British National Diet and Nutrition Survey 2000–2001.

Primary outcomes

Participants’ sodium intake measured both with a 7-day dietary record and a 24-h urine collection. By accounting for important linear and non-linear risk factors and spatial effects, the geographical difference and spatial patterns of both dietary sodium intake and 24-h urinary sodium were investigated using Bayesian geo-additive models via Markov Chain Monte Carlo simulations.

Results

A significant north–south pattern of sodium intake was found from posterior probability maps after controlling for important sociodemographic factors. Participants living in Scotland had a significantly higher dietary sodium intake and 24-h urinary sodium levels. Significantly higher sodium intake was also found in people with the lowest educational attainment (dietary sodium: coeff. 0.157 (90% credible intervals 0.003, 0.319), urinary sodium: 0.149 (0.024, 0.281)) and in manual occupations (urinary sodium: 0.083 (0.004, 0.160)). These coefficients indicate approximately a 5%, 9% and 4% difference in average sodium intake between socioeconomic groups.

Conclusions

People living in Scotland had higher salt intake than those in England and Wales. Measures of low socioeconomic position were associated with higher levels of sodium intake, after allowing for geographic location.
Cognitive appraisals, objectivity and coping in ambulance workers: a pilot study
Authors: Shepherd Laura , Wild Jennifer
Published: January 2013

Objectives

Ambulance workers are regularly exposed to call-outs, which are potentially psychologically traumatic. The ability to remain objective and make adaptive appraisals during call-outs may be beneficial to this at-risk population. This pilot study investigated the links between cognitive appraisals, objectivity and coping in ambulance workers.

Methods

Forty-five ambulance workers from the London Ambulance Service, UK, were studied. Trauma exposure, post-traumatic stress disorder and depression symptoms were assessed using self-report measures. Positive and negative appraisals were measured in relation to two previous call-outs: one during which they coped well and one during which they did not.

Results

Enhanced coping was associated with making more positive appraisals during the call-out. Better coping was also related to greater levels of objectivity during these call-outs. Coping less well was associated with the use of more negative appraisals during the call-out.

Conclusions

Ambulance workers may benefit from psychological interventions, which focus on cognitive reappraisal and enhancing objectivity to improve coping and resilience.
The use of the laryngeal tube disposable by paramedics during out-of-hospital cardiac arrest: a prospectively observational study (2008–2012)
Authors: Müller Jens-Uwe , Semmel Thomas , Stepan Roland , Seyfried Timo F , Popov Aron F , Graf Bernhard M , Wiese Christoph H R
Published: January 2013

In the previous and the current guidelines of the European Resuscitation Council (ERC), endotracheal intubation (ETI), as an instrument for ventilation during resuscitation, was confirmed as less important for paramedics not trained in this method. For those, during resuscitation, the laryngeal tube is recommended by the ERC as a supraglottic airway device. The present study investigated prospectively the use of the laryngeal tube disposable (LT-D) by paramedics in prehospital emergency cases.

Methods

During a 42-month period (Sept 2008–Feb 2012), we prospectively registered all prehospital cardiac arrest situations in which the LT-D had been applied by paramedics (from one emergency medical service in Germany).

Results

During the defined period, 133 attempts, recorded on standardised data sheets, were enrolled into the investigation. Three were excluded from the study because of use during a trauma situation. Therefore, 130 patients were evaluated in this study. For this, the LT-D was used in 98% of all cases during resuscitation, and in about 2% of other emergencies (eg, trauma). With regard to resuscitation, adequate ventilation/oxygenation was described as possible in 83% of all included cases. In 66% of all cases, no problems concerning the insertion of the LT-D were described by the paramedics. No significant problems were reported in 93%. In 7% (n=9 cases), no insertion of the LT-D was possible. Instead of bag-mask-valve ventilation, the LT-D was used as a first-line airway device in about 66%. Between the two defined groups, no statistically significant differences were found (p>0.05).

Conclusions

As an alternative airway device during resuscitation, recommended by the ERC in 2005 and 2010, the LT-D may enable ventilation rapidly and, as in most of our described cases, effectively. Additionally, by using the LT-D in a case of cardiac arrest, a reduced ‘hands-off time’ and, therefore, a high chest compression rate may be possible. Our investigation showed that the LT-D was often used as an alternative to bag-mask-ventilation and to ETI as well. However, we were able to describe more problems in the use of the LT-D than earlier investigations. Therefore, in future, more studies concerning the use of alternative airway devices in comparison with ETI and/or video-laryngoscopy seem to be necessary.
Storage and safe use of medicines on farm
Authors: Carr John , Smith Jenny
Published: January 2013

To ensure the safety of staff and animals on farm, all medicines need to be stored in a safe place, labelled appropriately, kept at the recommended temperature, transported carefully and administered according to the manufacturers' instructions. Giving examples of both good and bad practice, John Carr and Jenny Smith describe the precautions that should be taken by farm staff and veterinary surgeons when handling medicines to maintain a safe working environment and provide the best animal care.
MRSA in horses
Authors: Heller Jane , Hughes Kris
Published: January 2013

Meticillin‐resistant Staphylococcus aureus (MRSA) is an emerging pathogen of clinical importance to many species, including horses. This article describes the clinical signs, diagnosis and treatment of this infection in horses, as well as considering the risks to people.
Surviving weather extremes: considerations for practices
Authors: Richards Iain
Published: January 2013

Extremes in weather, such as flooding, high winds, heat waves, deep snow and ice, can present different problems for vets having to work in such conditions, and practice managers have a duty to ensure a safe environment for their staff and clients. Iain Richards discusses some extreme weather scenarios and the hazards associated with them, and the importance of being prepared.
Establishing veterinary education in North America
Authors: Jones Bruce Vivash
Published: January 2013

The American Veterinary Medical Association is marking its 150th anniversary in 2013, celebrating ‘150 years of education, science and service’. As Bruce Vivash Jones explains, veterinary surgeons from the UK played a key role in establishing a system of veterinary education in North America
L-364,373 (R-L3) enantiomers have opposite modulating effects on IKs in mammalian ventricular myocytes
Authors: Corici Claudia , Kohajda Zsófia , Kristóf Attila , Horváth András , Virág László , Szél Tamás , Nagy Norbert , Szakonyi Zsolt , Fülöp Ferenc , Muntean Danina M. , Varró András , Jost Norbert
Published: January 2013

Activators of the slow delayed rectifier K+ current (IKs) have been suggested as promising tools for suppressing ventricular arrhythmias due to prolongation of repolarization. Recently, L-364,373 (R-L3) was nominated to activate IKs in myocytes from several species; however, in some studies, it failed to activate IKs. One later study suggested opposite modulating effects from the R-L3 enantiomers as a possible explanation for this discrepancy. Therefore, we analyzed the effect of the RL-3 enantiomers on IKs in ventricular mammalian myocytes, by applying standard microelectrode and whole-cell patch-clamp techniques at 37 °C. We synthesized 2 substances, ZS_1270B (right) and ZS_1271B (left), the 2 enantiomers of R-L3. In rabbit myocytes, ZS_1270B enhanced the IKs tail current by approximately 30%, whereas ZS_1271B reduced IKs tails by 45%. In guinea pig right ventricular preparations, ZS_1270B shortened APD90 (action potential duration measured at 90% repolarization) by 12%, whereas ZS_1271B lengthened it by approximately 15%. We concluded that R-L3 enantiomers in the same concentration range indeed have opposite modulating effects on IKs, which may explain why the racemic drug R-L3 previously failed to activate IKs. ZS_1270B is a potent IKs activator, therefore, this substance is appropriate to test whether IKs activators are ideal tools to suppress ventricular arrhythmias originating from prolongation of action potentials.
An igneous-textured clast in the Peace River meteorite: insights into accretion and metamorphism of asteroids in the early solar system
Authors: Herd Christopher D.K. , Friedrich Jon M. , Greenwood Richard C. , Franchi Ian A.
Published: January 2013

The mineralogy, petrology, and geochemistry of an igneous-textured clast in the Peace River L6 chondrite meteorite was examined to determine the roles of nebular processes, accretion, and parent-body metamorphism in its origin. The centimetre-scale clast is grey and fine grained and is in sharp contact with the host chondrite. Two sub-millimetre veins cut across both the clast and host, indicating that the clast formed prior to the impact (shock) event(s) that produced the numerous veins present in the Peace River meteorite. The clast and host are indistinguishable in terms of mineral compositions. In contrast, there are differences in modal mineralogy, texture, as well as trace element and oxygen isotope composition between the clast and host. These differences strongly suggest that the clast was formed by impact melting of LL-group chondritic material involving loss of Fe–FeS and phosphate components, followed by relatively rapid cooling and incorporation into the Peace River host meteorite. Subsequent metamorphism on the Peace River parent body caused recrystallization of the clast and homogenization of mineral compositions and thermally labile element abundances between the clast and host. Shock metamorphism, including formation of shock melt veins, occurred post-metamorphism, during fragmentation of the L chondrite parent body. The results suggest that the formation of the Peace River parent asteroid included the incorporation of material from other asteroids and that the pre-metamorphic protolith was a breccia. Accordingly, we propose that the Peace River meteorite be reclassified as a polymict breccia.
BAYESIAN IMPLICATIONS OF COLLIDER AND SUSY DARK MATTER DIRECT AND INDIRECT SEARCHES
Authors: ROSZKOWSKI LESZEK , SESSOLO ENRICO MARIA , TSAI YUE-LIN SMING
Published: January 2013

In this talk we present our recent Bayesian analyses of the Constrained MSSM in which the model's parameter space is constrained by the CMS αT 1.1/fb data at the LHC, the XENON100 dark matter direct detection data, and Fermi-LAT γ-ray data from dwarf spheroidal galaxies (dSphs). We also show that the projected one-year sensitivities for annihilation-induced neutrinos from the Sun in the 86-string configuration of IceCube/DeepCore have the potential to yield additional constraining power on the parameter space of the CMSSM.
BLACK HOLES, THE GENERALIZED UNCERTAINTY PRINCIPLE AND HIGHER DIMENSIONS
Authors: CARR B. J.
Published: January 2013

We propose a new way in which black holes connect macrophysics and microphysics. The Generalized Uncertainty Principle suggests corrections to the Uncertainty Principle as the energy increases towards the Planck value. It also provides a natural transition between the expressions for the Compton wavelength below the Planck mass and the black hole event horizon size above it. This suggests corrections to the event horizon size as the black hole mass falls towards the Planck value, leading to the concept of a Generalized Event Horizon. Extrapolating this expression below the Planck mass suggests the existence of a new kind of black hole, whose size is of order its Compton wavelength. Recently it has been found that such a black hole solution is permitted by loop quantum gravity, its unusual properties deriving from the fact that it is hidden behind the throat of a wormhole. This has important implications for the formation and evaporation of black holes in the early Universe, especially if there are extra spatial dimensions.
BIRACK MODULES AND THEIR LINK INVARIANTS
Authors: BAUERNSCHMIDT REGINA , NELSON SAM
Published: January 2013

We extend the rack algebra ℤ[X] defined by Andruskiewitsch and Graña to the case of biracks, enabling a notion of birack modules. We use these birack modules to define an enhancement of the birack counting invariant generalizing the birack module counting invariant in [A. Haas, G. Heckel, S. Nelson, J. Yuen and Q. Zhang, Rack module enhancements of counting invariants, Osaka J. Math.49 (2012) 471–488]. We provide examples demonstrating that the enhanced invariant is not determined by the Jones or Alexander polynomials and is stronger than the unenhanced birack counting invariant.
DFT INSIGHT INTO THE UV-VIS SPECTRA AND RADICAL SCAVENGING ACTIVITY OF AURANTIO-OBTUSIN
Authors: XU SI-CONG , REN YI , WAN LI , LI WAI-KEE , WONG NING-BEW , ZHANG JIA-XIONG , LIAO QING , JI LANG
Published: January 2013

Aurantio-obtusin (2,6,8-trihydroxy-1,7-dimethoxy-3-methyl anthraquinone), an anthraquinone derivative isolated from the seeds of Cassia tora L., has been studied by DFT calculations at the B3LYP/6-311+g(2df,p)//B3LYP/6–31G(d,p) level in vacuum and in methanol polarized continuum model (PCM). Eight conformers have been located by conformational search and optimization. Our results indicate that the titled compound has planar structures, and five intramolecular hydrogen bonds are found in the lowest-energy structure, including three OH⋯O and two CH⋯O hydrogen bonds. The electronic spectra in methanol have been determined by the time-dependent density functional theory (TD-DFT) approach, showing that the first singlet exited state of the title compound arises from π → π* electron transition. The antioxidant activity of aurantio-obtusin is evaluated by means of calculating O−H bond dissociated enthalpy (BDE) and the adiabatic ionization energy (IE). The calculated BDE and IE values of aurantio-obtusin are 341.8 and 732.3 kJ mol-1, respectively, lower than the corresponding values of phenol (348.4 and 801.7 kJ mol-1) and purpurin (360.4 and 747.8 kJ mol-1), suggesting that aurantio-obtusin is a better antioxidant.
GENOME-WIDE ANALYSIS AND MODELING OF DNA METHYLATION SUSCEPTIBILITY IN 30 BREAST CANCER CELL LINES BY USING CpG FLANKING SEQUENCES
Authors: AN JAEHYUN , KIM KWANGSOO , RHEE SUNG-MIN , CHAE HEEJOON , NEPHEW KENNETH P. , KIM SUN
Published: January 2013

DNA methylation is an epigenetic modification of DNA that adds a methyl group to cytosine. Aberrant DNA methylation in the CpG context is frequently observed in cancer cells and it is known that aberrant DNA methylation silences tumor repressor genes. However, the mechanism of DNA methylation is not well understood. A widely accepted hypothesis is that DNA methylation does not randomly occur and may be controlled by some instructive mechanisms. In this paper, we conducted an extensive study on this important question by using proprietary sequencing data from methyl-binding domain protein (MBD)-Cap ChIP sequencing experiments for 30 breast cancer cell lines. The goal of our study is to investigate difference in nucleotide composition around CpG sites, where high levels of methylation are observed, and use the information for modeling DNA methylation susceptibility. First, we observed that DNA methylation is not uniform in the whole-genome region and also that the character composition of CpG flanking sequences are significantly different between hyper- and hypo-methylated groups. In an in-depth study, we used information theoretic approaches such as entropy and relative entropy to delineate character composition features and found enrichment of A (Adenine) and T (Thymine) in specific positions around hyper-methylated sites. As the methylation level is increased, A, T proportions in specific positions around hypermethylated sites are increased while A, T proportions in other positions around hypermethylated sites are decreased. Second, we built predictive models for methylation susceptibility by using characters flanking CpG sites as features and hyper-/hypo-methylation status as class. Third, we constructed predictive models using a log odds score of two profiles from DNA sequences surrounding CpG sites of hyper- and hypo-methylated groups. This analysis showed that distribution of profile scores of hyper-/hypo-methylated sites sequences is quite distinct. Our genome-wide CpG methylation study shows that nucleotides around CpG sites caries information for cytosine methylation. This is consistent with the seminal work on the instructive evidence of DNA methylation by Keshet et al. (Nature Genetics, 38(2), 149–153 2006). Our study is on the full genome scale and used the sequencing data, thus our study is significantly different in terms of resolution of data and analysis methods used for the study by Keshet et al.