bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved health or improved decision making? The ethical goals of EBM
Authors: Gupta Mona
Published: August 2011

Evidence‐based medicine (EBM) is frequently portrayed as a value‐free approach to knowing what kinds of treatment ‘really work.’ Since practitioners should help patients to improve their health, and EBM tells us which interventions will work, then it follows that wemustpractice EBM, offering only those interventions supported by evidence. The primary goal of EBM, then, is an ethical one – to improve health. More recently, EBM's authors have also committed themselves to ‘shared decision making’ in which evidence plays a role in the clinical encounter, but where patients, motivated by their own values, should have final decision‐making authority. Envisioned this way, strengthening the informed consent process, rather than improved health per se, is viewed as the goal of EBM. In this paper, I will explore this shift in EBM's ethics from the goal of improved health towards the goal of strengthened informed consent. Drawing upon data from a qualitative enquiry of scholars involved in the development of EBM, I will argue that EBM is now committed tobothof these ethical goals. Where they conflict, the aim of the intervention will determine which goal practitioners should pursue. Having increased the ethical complexity of EBM, we are left with the question of whether EBM would still be judged a success if it did not lead to much in the way of improvements in health, but primarily strengthened informed consent. This paper will conclude by arguing that this more nuanced version of EBM's ethics accurately reflects the dynamics of real clinical practice but undermines the original, perceived need for EBM.
Validity and reliability study on traditional Chinese FACT‐C in Chinese patients with colorectal neoplasm
Authors: Wong Carlos K. H. , Lam Cindy L. K. , Law Wai‐Lun , Poon Jensen T. C. , Chan Pierre , Kwong Dora L. W. , Tsang Janice
Published: August 2011

Objective  To establish the validity and reliability of traditional Chinese version of the Functional Assessment of Cancer Therapy‐Colorectal (FACT‐C).

Methods  A total of 536 subjects self‐administered (n = 331) or interviewer‐administered (n = 205) FACT‐C (version 4), EORTC QLQ‐C30/CR38 and SF‐12v2 instruments for health‐related quality of life assessment. Construct validity was examined by item–scale correlation, scaling success and concurrent validity. Reliability was evaluated by test–retest reliability and internal consistency. Sensitivity was assessed by known‐groups comparisons.

Results  The completion rates for FACT‐C were almost perfect (>98%). The FACT‐C demonstrated item‐internal consistency and item discriminant validity through item–scale correlation. Scaling success and concurrent validity were satisfactory to support the construct validity. The five subscales of the FACT‐C showed good internal consistency with Cronbach alpha coefficient and substantial reproducibility, demonstrating good reliability. Sensitivity was supported when there were significant differences in scores related to physical condition between patients who were receiving treatment and those who were not.

Conclusion  Traditional Chinese version of the FACT‐C was demonstrated to have satisfactory psychometric properties in terms of applicability, reliability, validity and sensitivity in Chinese patients with colorectal neoplasm. The FACT‐C was valid colorectal‐specific health‐related quality of life tool for the Chinese population.
Development of the vagal innervation of the gut: steering the wandering nerve
Authors: Ratcliffe E. M. , Farrar N. R. , Fox E. A.
Published: August 2011

Background  The vagus nerve is the major neural connection between the gastrointestinal tract and the central nervous system. During fetal development, axons from the cell bodies of the nodose ganglia and the dorsal motor nucleus grow into the gut to find their enteric targets, providing the vagal sensory and motor innervations respectively. Vagal sensory and motor axons innervate selective targets, suggesting a role for guidance cues in the establishment of the normal pattern of enteric vagal innervation.

Purpose  This review explores known molecular mechanisms that guide vagal innervation in the gastrointestinal tract. Guidance and growth factors, such as netrin‐1 and its receptor, deleted in colorectal cancer, extracellular matrix molecules, such as laminin‐111, and members of the neurotrophin family of molecules, such as brain‐derived neurotrophic factor have been identified as mediating the guidance of vagal axons to the fetal mouse gut. In addition to increasing our understanding of the development of enteric innervation, studies of vagal development may also reveal clinically relevant insights into the underlying mechanisms of vago‐vagal communication with the gastrointestinal tract.
Functional genomics of dichloromethane utilization in Methylobacterium extorquens DM4
Authors: Muller Emilie E. L. , Hourcade Edith , Louhichi‐Jelail Yousra , Hammann Philippe , Vuilleumier Stéphane , Bringel Françoise
Published: August 2011

Dichloromethane (CH2Cl2, DCM) is a chlorinated solvent mainly produced by industry, and a common pollutant. Some aerobic methylotrophic bacteria are able to grow with this chlorinated methane as their sole carbon and energy source, using a DCM dehalogenase/glutathione S‐transferase encoded by dcmA to transform DCM into two molecules of HCl and one molecule of formaldehyde, a toxic intermediate of methylotrophic metabolism. In Methylobacterium extorquens DM4 of known genome sequence, dcmA lies on a 126 kb dcm genomic island not found so far in other DCM‐dechlorinating strains. An experimental search for the molecular determinants involved in specific cellular responses of strain DM4 growing with DCM was performed. Random mutagenesis with a minitransposon containing a promoterless reporter gfp gene yielded 25 dcm mutants with a specific DCM‐associated phenotype. Differential proteomic analysis of cultures grown with DCM and with methanol defined 38 differentially abundant proteins. The 5.5 kb dcm islet directly involved in DCM dehalogenation is the only one of seven gene clusters specific to the DCM response to be localized within the dcm genomic island. The DCM response was shown to involve mainly the core genome of Methylobacterium extorquens, providing new insights on DCM‐dependent adjustments of C1 metabolism and gene regulation, and suggesting a specific stress response of Methylobacterium during growth with DCM. Fatty acid, hopanoid and peptidoglycan metabolisms were affected, hinting at the membrane‐active effects of DCM due to its solvent properties. A chloride‐induced efflux transporter termed CliABC was also newly identified. Thus, DCM dechlorination driven by the dcm islet elicits a complex adaptive response encoded by the core genome common to dechlorinating as well as non‐dechlorinating Methylobacterium strains.
Structural, mass and elemental analyses of storage granules in methanogenic archaeal cells
Authors: Toso Daniel B. , Henstra Anne M. , Gunsalus Robert P. , Zhou Z. Hong
Published: August 2011

Storage granules are an important component of metabolism in many organisms spanning the bacterial, eukaryal and archaeal domains, but systematic analysis of their organization inside cells is lacking. In this study, we identify and characterize granule‐like inclusion bodies in a methanogenic archaeon, Methanospirillum hungatei, an anaerobic microorganism that plays an important role in nutrient recycling in the ecosystem. Using cryo electron microscopy, we show that granules in mature M. hungatei are amorphous in structure with a uniform size. Energy dispersive X‐ray spectroscopy analysis establishes that each granule is a polyphosphate body (PPB) that consists of high concentrations of phosphorous and oxygen, and increased levels of iron and magnesium. By scanning transmission electron tomography, we further estimate that the mass density within a PPB is a little less than metal titanium at room temperature and is about four times higher than that of the surrounding cytoplasm. Finally, three‐dimensional cryo electron tomography reveals that PPBs are positioned off‐centre in their radial locations relative to the cylindrical axis of the cell, and almost uniformly placed near cell ends. This positioning ability points to a genetic program that spatially and temporally directs the accumulation of polyphosphate into a storage granule, perhaps for energy‐consuming activities, such as cell maintenance, division or motility.
Household Liquidity and Incremental Financing Decisions: Theory and Evidence
Authors: Cunha M. Ricardo , Lambrecht Bart M. , Pawlina Grzegorz
Published: August 2011

Abstract:  In this paper we develop a stochastic model for household liquidity. In the model, the optimal liquidity policy takes the form of a liquidity range. Subsequently, we use the model to calibrate the upper bound of the predicted liquidity range. Equipped with knowledge about the relevant control barriers, we run a series of empirical tests on a panel data set of Dutch households covering the period 1992‐2007. The results broadly validate our theoretical predictions that households (i) exhaust most of their short‐term liquid assets prior to increasing net debt, and (ii) reduce outstanding net debt at the optimally selected upper liquidity barrier. However, a small minority of households appear to act sub‐optimally. Poor and vulnerable households rely too frequently on expensive forms of credit (such as overdrafts) hereby incurring substantial amounts of fees and fixed borrowing costs. Elderly households and people on social benefits tend to accumulate too much liquidity. Finally, some households take on expensive short‐term credit while having substantial amounts of low‐yielding liquid assets.
Rivaroxaban for the prevention and treatment of venous thromboembolism
Authors: Turpie Alexander G.G.
Published: August 2011

Venous thromboembolism (VTE) is a common and often life‐threatening cardiovascular disorder. Patients undergoing total hip replacement or total knee replacement surgery are at increased risk of VTE. In this setting, clinical practice guidelines recommend the use of low molecular weight heparins, vitamin K antagonists or fondaparinux for the prevention of VTE. However, the use of these anticoagulants is beset by practical difficulties that reduce compliance to therapy and adherence to recommended guidelines. New oral anticoagulants (OACs) that are administered in fixed doses without the need for monitoring are now being introduced to clinical practice. Rivaroxaban, dabigatran and apixaban are either approved or in advanced stages of clinical development for the prevention and/or treatment of VTE. This article provides an overview of the phase III clinical development programmes for these novel OACs, with special focus on rivaroxaban. With encouraging data already emerging, the promise of a simplified single‐drug approach for VTE treatment is on the horizon.
Response patterns to bronchodilator and quantitative computed tomography in chronic obstructive pulmonary disease
Authors: Lee Jae Seung , Huh Jin Won , Chae Eun Jin , Seo Joon Beom , Ra Seung Won , Lee Ji‐Hyun , Kim Eun‐Kyung , Lee Young Kyung , Kim Tae‐Hyung , Kim Woo Jin , Lee Jin Hwa , Lee Sang‐Min , Lee Sangyeub , Lim Seong Yong , Shin Tae Rim , Yoon Ho Il , Sheen Seung Soo , Oh Yeon‐Mok , Lee Sang‐Do
Published: August 2011

Background:  Patients with chronic obstructive pulmonary disease (COPD) show different spirometric response patterns to bronchodilator, such that some patients show improvement principally in expiratory flow (forced expiratory volume in 1 s; FEV1), whereas others respond by improvement of lung volume (forced vital capacity; FVC). The mechanisms of these different response patterns to bronchodilator remain unclear. We investigated the associations between bronchodilator responsiveness and quantitative computed tomography (CT) indices in patients with COPD.

Methods:  Data on a total of 101 patients with stable COPD were retrospectively analysed. Volume and flow responses to bronchodilator were assessed by FVC and FEV1 changes before and after inhalation of salbutamol (400 μg). Volumetric CT was performed to quantify emphysema, air trapping and large airway thickness. Emphysema was assessed by the volume fraction of the lung under −950 Hounsfield units (HU; V950) at full inspiration and air trapping by the ratio of mean lung density (MLD) at full expiration and inspiration. Airway wall thickness and wall area percentage (WA%; defined as wall area/[wall area + lumen area] × 100), were measured near the origin of right apical and left apico‐posterior bronchus.

Results:  Among quantitative CT indices, the CT emphysema index (V950 insp) showed a significant negative correlation with postbronchodilator FEV1 change (R = −0·213, P = 0·004), and the CT air‐trapping index correlated positively with postbronchodilator FVC change(R = 0·286, P≤0·001). Multiple linear regression analysis showed that CT emphysema index had independent association with postbronchodilator FEV1 change and CT air‐trapping index with postbronchodilator FVC change.

Conclusion:  The degrees of emphysema and air trapping may contribute to the different response patterns to bronchodilator in patients with COPD.
Impact of technical assistants for venepuncture and intravenous cannulation on overall emergency department performance
Authors: Dinh Michael M , Green Timothy C , Newsome David , Bein Kendall J
Published: August 2011

Objective: The objective of the article was to determine the effect of a technical assistant for venepuncture and i.v. cannulation on triage performance and patient length of stay in an ED.

Methods: An observational study of daily ED performance was conducted at an inner city tertiary referral ED. Over a period of 158 consecutive days, data on triage performance and average length of stay were collected. A technical assistant was employed for 8–10 h per day to perform venepuncture, i.v. cannulation and electronic order entry. Study groups compared were days staffed by a technical assistant and days that were not staffed.

Results: Days staffed by a technical assistant were associated with significantly higher triage performance for triage category three (mean 0.66, 95% CI 0.63–0.69 vs 0.58, 95% CI 0.54–0.62; P= 0.003) and lower average length of stay per patient for triage category two patients (mean length of stay 390 min, 95% CI 369–411 vs 425 min, 95% CI 399–451; P= 0.04). Triage performance thresholds for triage category three (75% of patients seen within 30 min) were met over twice as often on staffed days compared with control (39/96 [38%]vs 10/62 [16%], P= 0.004).

Conclusion: Staffing the ED with a technical assistant was associated with improved ED performance for triage category three and average length of stay for triage category two patients.
Pain, analgesia and genetics
Authors: Muralidharan Arjun , Smith Maree T
Published: August 2011

Objectives

In the clinical setting, there is marked intersubject variability in the intensity of pain reported by patients with apparently similar pain states, as well as widely differing analgesic dosing requirements between individuals to produce satisfactory pain relief with tolerable side-effects. Genetic and environmental factors as well as their interaction are implicated, and these are discussed in this review.

Key findings

Pioneering work undertaken in mice more than a decade ago, showed a strong genetic contribution to levels of nociception/hypersensitivity as well as levels of antinociception produced by commonly available analgesic agents. To date more than 300 candidate ‘pain’ genes have been identified as potentially contributing to heritable differences in pain sensitivity and analgesic responsiveness in animals and humans, with this information available in a publicly accessible database http://www.jbldesign.com/jmogil/enter.html. Since then, many genetic association studies have been conducted in humans to investigate the possibility that single nucleotide polymorphisms (SNPs) in an individual gene may explain drug inefficacy or excessive toxicity experienced by a small subset of the whole population who have the rare allele for a particular SNP.

Despite the fact that SNPs in more than 20 genes that affect pain sensitivity or contribute to interindividual variability in responses to analgesic medications have been identified in the human genome, much of the data is conflicting. Apart from deficiencies in the design and conduct of human genetic association studies, recent research from other fields has implicated epigenetic mechanisms that facilitate dynamic gene-environment communication, as a possible explanation.
Azithromycin suppresses proliferation, interleukin production and mitogen-activated protein kinases in human peripheral-blood mononuclear cells stimulated with bacterial superantigen
Authors: Hiwatashi Yoko , Maeda Masaki , Fukushima Hisayo , Onda Kenji , Tanaka Sachiko , Utsumi Hiroya , Hirano Toshihiko
Published: August 2011

Objectives

Macrolide antibiotics are used for the treatment of immunological disorders such as psoriasis. However, few studies have investigated the immunoregulatory efficacy of macrolides in bacterial superantigen-stimulated immune cells.

Methods

The suppressive efficacies of azithromycin, clarithromycin, roxithromycin and prednisolone were evaluated in vitro against the concanavalin A- or toxic shock syndrome toxin 1 (TSST-1)-induced proliferation of peripheral-blood mononuclear cells (PBMCs) obtained from nine healthy subjects. The concentrations of six cytokines in a PBMC-culture medium were measured using bead-array procedures followed by flow cytometry. Cellular c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activity were measured using cell-based ELISA procedures.

Key findings

Azithromycin, clarithromycin and roxithromycin inhibited the proliferation of both the concanavalin A- and superantigen-stimulated PBMCs dose-dependently. The effect of azithromycin was the strongest, with IC50 values of less than 5 µg/ml. Furthermore, the suppressive efficacy of prednisolone against concanavalin A- or TSST-1-stimulated PBMCs was significantly promoted in combination with 5 µg/ml azithromycin (P < 0.002). The concentrations of TNF-α, interleukin (IL)-2, −4, −5 and −10 in the supernatant of concanavalin A- or TSST-1-stimulated PBMCs cultured for 72 h decreased by 65–98% in the presence of 5 µg/ml azithromycin. The stimulation of PBMCs with concanavalin A or TSST-1 increased cellular JNK and ERK activity, and 5 µg/ml azithromycin significantly attenuated the increased activity of JNK in the TSST-1-stimulated cells and ERK in the concanavalin A- and TSST-1-stimulated PBMCs, respectively (P < 0.05).

Conclusions

Azithromycin suppresses mitogen- or superantigen-induced proliferation of PBMCs by possibly inhibiting both cellular JNK and ERK activity.
Myrtenal inhibits acetylcholinesterase, a known Alzheimer target
Authors: Kaufmann Dorothea , Dogra Anudeep Kaur , Wink Michael
Published: August 2011

Objectives

Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer's disease. In this study selected components of essential oils, which carry a variety of important functional groups, were tested for their in-vitro anti-acetylcholinesterase activity.

Methods

In-vitro anti-acetylcholinesterase activity was measured by an adapted version of Ellman's colorimetric assay.

Key findings

1,8-cineole, carvacrol, myrtenal and verbenone apparently inhibited AChE; the highest inhibitory activity was observed for myrtenal (IC50 = 0.17 mm). This is the first study showing the AChE inhibitory activity of myrtenal.

Conclusions

Our investigations provided evidence for the efficacy of monoterpenes as inhibitors of AChE.
Experimental Analysis, Modeling, and Control of Volumetric Radial-Piston Pumps
Authors: Catania Andrea E. , Ferrari Alessandro
Published: August 2011

An experimental-theoretical study has been carried out on high-pressure volumetric radial-piston pumps for diesel fuel injection systems. The dependence of the pump inducted flow rate on speed and load was investigated and the characteristic curve of the pump cooling-lubrication circuit was derived. The head-capacity curves were determined for different types of pumps at different revolution speeds and compared with the injector flow requirements in order to evaluate the pressure-control strategy efficiency. An insight into the ageing effects on the pump performance was also provided. Furthermore, the dynamic pump behavior was investigated, with specific reference to the flow-rate ripple at the delivery port. A general analytical expression has been derived for the volumetric efficiency. Furthermore, a specific procedure has been developed and applied to the experimental evaluation of the fuel leakages in pressure control valve (PCV) integrated pumps. Finally, the mechanical-hydraulic efficiency of the pump has experimentally been assessed as a function of head and speed in order to obtain a reliable evaluation of the pump shaft power and torque at different working conditions.
A Micro Investigation Into Electro Discharge Machining Industrial Applications Processing Parameters and Product Surface Profile Using Piezoelectric Ultrasonic Feed Drive
Authors: Shafik M. , Abdalla H. S. , Wilmshurst T. J.
Published: August 2011

This paper presents a micro investigation into electrodischarge-machining system, using piezoelectric ultrasonic motor feed drive. The drive was designed to improve the electrodischarge-machining servo control system stability of machining, quality of surface profiles of the machined products, and system dynamic time response. Research has been undertaken to examine the developed servo control feed drive in two industrial applications, electrodischarge-machining, and electrodischarge-texturing. Two arrangements were used, in this investigation. The existing servo control feed drive system, which uses a dc servomotor, and the developed system, which uses piezoelectric feed drive. The electrodischarge machining parameters including current level, on-off time, and duty cycle of the machining pulse were the main machining parameters of this investigation. The electron microscopic micro investigation into the machined samples showed that: piezoelectric ultrasonic feed drive showed a clear improvement in the quality of surface finish of the machined samples, due to the fast dynamic time response of the ultrasonic feed drive. This was accompanied by a notable reduction in the arcing and short-circuiting teething processes. This was verified by examining the electrode movements, the variations in the interelectrode gap voltage, current, and feedback control signals.
Recently Formed Polyploid Plants Diversify at Lower Rates
Authors: Mayrose Itay , Zhan Shing H. , Rothfels Carl J. , Magnuson-Ford Karen , Barker Michael S. , Rieseberg Loren H. , Otto Sarah P.
Published: August 2011

The doubling of genomes does not cause increased plant speciation unless the progenitor lineages are highly fit.
Ice Flow of the Antarctic Ice Sheet
Authors: Rignot E. , Mouginot J. , Scheuchl B.
Published: August 2011

A high-resolution map of ice motion in Antarctica shows the details of ice movement in a warming climate.
Unfolded Proteins Are Ire1-Activating Ligands That Directly Induce the Unfolded Protein Response
Authors: Gardner Brooke M. , Walter Peter
Published: August 2011

A newly synthesized secretory protein quality control pathway is activated by direct binding of misfolded proteins to a sensor in the endoplasmic reticulum.
Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models
Authors: Khodai Tansi , Chappell Debbie , Christy Clare , Cockle Paul , Eyles Jim , Hammond Daisy , Gore Katrina , McCluskie Michael J. , Evans Dana M. , Lang Susanne , Loudon Peter T. , Townend Tim , Wright Paul , West Kate , Bright Helen
Published: August 2011

Despite several attempts to develop an effective prophylactic vaccine for HSV-2, all have failed to show efficacy in the clinic. The most recent of these failures was the GlaxoSmithKline (GSK) subunit vaccine based on the glycoprotein gD with the adjuvant monophosphoryl lipid A (MPL). In a phase 3 clinical trial, this vaccine failed to protect from HSV-2 disease, even though good neutralizing antibody responses were elicited. We aimed to develop a superior, novel HSV-2 vaccine containing either gD or gB alone or in combination, together with the potent adjuvant CpG oligodeoxynucleotides (CPG). The immunogenic properties of these vaccines were compared in mice. We show that gB/CPG/alum elicited a neutralizing antibody response similar to that elicited by gD/CPG/alum vaccine but a significantly greater gamma interferon (IFN-γ) T cell response. Furthermore, the combined gB-gD/CPG/alum vaccine elicited significantly greater neutralizing antibody and T cell responses than gD/MPL/alum. The efficacies of these candidate vaccines were compared in the mouse and guinea pig disease models, including a novel male guinea pig genital disease model. These studies demonstrated that increased immune response did not correlate to improved protection. First, despite a lower IFN-γ T cell response, the gD/CPG/alum vaccine was more effective than gB/CPG/alum in mice. Furthermore, the gB-gD/CPG/alum vaccine was no more effective than gD/MPL/alum in mice or male guinea pigs. We conclude that difficulties in correlating immune responses to efficacy in animal models will act as a deterrent to researchers attempting to develop effective HSV vaccines.
Evaluation of the Recombinant 10-Kilodalton Immunodominant Region of the BP26 Protein of Brucella abortus for Specific Diagnosis of Bovine Brucellosis
Authors: Tiwari Arvind Kumar , Kumar Subodh , Pal Vijai , Bhardwaj Bhupendra , Rai Ganga Prasad
Published: August 2011

Brucellosis is a disease with worldwide distribution affecting animals and human beings.Brucella abortusis the causative agent of bovine brucellosis. The cross-reactions of currently available diagnostic procedures forB. abortusinfection result in false-positive reactions, which make the procedures unreliable. These tests are also unable to differentiateBrucella-infected and -vaccinated animals. The present work is focused on the use of a nonlipopolysaccharide (LPS) diagnostic antigen, a recombinant 10-kDa (r10-kDa) protein ofB. abortus, for specific diagnosis of brucellosis. The purified recombinant protein was used as a diagnostic antigen in plate enzyme-linked immunosorbent assay (p-ELISA) format to screen 408 bovine serum samples (70 presumptively negative, 308 random, and 30 vaccinated), and the results were compared with those of the Rose Bengal plate agglutination test (RBPT) and the standard tube agglutination test (STAT). Statistical analysis in presumptive negative samples revealed 100 and 98.41% specificity of p-ELISA with RBPT and STAT, and an agreement of 91.43% with the tests using Cohen's kappa statistics. In random samples, the agreement of p-ELISA was 77.92% and 80.52% with RBPT and STAT, respectively. p-ELISA investigation of vaccinated samples reported no false-positive results, whereas RBPT and STAT reported 30% and 96.6% false-positive results, respectively. The data suggest that p-ELISA with r10-kDa protein may be a useful method for diagnosis of bovine brucellosis. Furthermore, p-ELISA may also be used as a tool for differentiatingBrucella-vaccinated and naturally infected animals.
Refinement of a Human Challenge Model for Evaluation of Enterotoxigenic Escherichia coli Vaccines
Authors: Harro Clayton , Chakraborty Subhra , Feller Andrea , DeNearing Barbara , Cage Alicia , Ram Malathi , Lundgren Anna , Svennerholm Ann-Mari , Bourgeois August L. , Walker Richard I. , Sack David A.
Published: August 2011

EnterotoxigenicEscherichia coli(ETEC) strain H10407 (serotype O78:H11 producing heat-labile toxin [LT], heat-stable toxin [ST], and colonization factor I [CFA/I]) induces reliably high diarrheal attack rates (ARs) in a human challenge model at doses of ≥109CFU. A descending-dose challenge study was conducted with changes to the standard fasting time and buffer formulation, seeking conditions that permit lower inocula while maintaining reproducibly high ARs. In cohort 1, 20 subjects were fasted overnight and randomized 1:1:1:1 to receive H10407 at doses of 108CFU with bicarbonate, 108CFU with CeraVacx, 107CFU with bicarbonate, or 107CFU with CeraVacx. Subsequent cohorts received H10407 (107CFU with bicarbonate) with similar fasting conditions. Cohort 2 included 15 ETEC-naïve volunteers. Cohort 3 included 10 ETEC-naïve volunteers and 10 rechallenged volunteers. In all, 25/35 (71%) ETEC-naïve recipients of 107CFU of H10407 developed moderate or severe diarrhea (average maximum stool output/24 h = 1,042 g), and most (97%) shed H10407 (maximum geometric mean titer = 7.5 × 107CFU/gram of stool). Only one of 10 rechallenged volunteers developed diarrhea. These rechallenged subjects had reduced intestinal colonization, reflected by quantitative microbiology of fecal samples. Among the 35 ETEC-naïve subjects, anti-lipopolysaccharide (LPS) O78 serum antibody responses were striking, with positive IgA and IgG antibody responses in 33/35 (94%) and 25/35 (71%), respectively. Anti-heat-labile enterotoxin (LTB) serum IgA and IgG responses developed in 19/35 (54%) and 14/35 (40%) subjects, respectively. Anti-CFA/I serum IgA and IgG responses were detected in 15/35 (43%) and 8/35 (23%) subjects. After the second challenge, participants exhibited blunted anti-LPS and -LTB responses but a booster response to CFA/I. This ETEC model should prove useful in the future evaluation of ETEC vaccine candidates.
Chronic hepatitis in the English springer spaniel: clinical presentation, histological description and outcome
Authors: Bexfield N. H. , Andres‐Abdo C. , Scase T. J. , Constantino‐Casas F. , Watson P. J.
Published: August 2011

Medical records and liver histology of 68 English springer spaniels (ESS) with a histological diagnosis of CH were reviewed retrospectively. PCR was performed on liver tissue for canine adenovirus‐1 (CAV‐1), canine parvovirus, canine herpesvirus and pathogenicLeptospiraspecies. Follow‐up information was obtained to calculate survival times. Median age at presentation was three years seven months (range, seven months to eight years five months) and there were 48 female and 20 male dogs. Clinical signs were non‐specific and five dogs were asymptomatic. All dogs had an increase in serum activity of one or more hepatobiliary enzymes. Histopathology demonstrated hepatocyte necrosis and apoptosis with varying amounts of fibrosis. A predominantly lymphoplasmacytic infiltrate throughout the hepatic parenchyma was found in all 68 dogs, but 45 of these dogs also had a neutrophilic component to the inflammatory infiltrate. There was no significant copper accumulation and no aetiological agent was identified by PCR. The median survival time was 189 days (range, 1 to 1211 days), 38 dogs died within three months and 12 dogs survived more than a year following diagnosis.
Capturing cold-stress-related sequence diversity from a wild relative of common bean (Phaseolus angustissimus)
Authors: Vijayan P. , Parkin I.A.P. , Karcz S.R. , McGowan K. , Vijayan K. , Vandenberg A. , Bett K.E.
Published: August 2011

One restriction to the cultivation of common bean, Phaseolus vulgaris L., is its limited tolerance to low temperatures. In the present study, subtraction suppression hybridization was employed to enrich for stress responsive genes in both a chilling-susceptible common bean and a relatively more chilling-tolerant wild bean species, Phaseolus angustissimus. For each species, approximately 11 000 expressed sequence tags were generated. Comparative sequence analysis of the EST collection with the available annotated genome sequences of the model Fabaceae species Medicago truncatula and Glycine max identified protein homologues for approximately 65% and 80% of the Phaseolus sequences, respectively. This difference reflects the closer phylogenetic relationship between the genera Phaseolus and Glycine compared with Medicago. Annotation of the Phaseolus sequences was facilitated through this comparative analysis and indicated that several heat shock proteins, cytochrome P450s, and DNA binding factors were uniquely found among the sequences from the wild species P. angustissimus. The Phaseolus sequences have been made available on a GBrowse implementation using M. truncatula as the reference genome, providing rapid access to the sequence data and associated comparative genome data.
Diversity and evolution of the Hordeum murinum polyploid complex in Algeria
Authors: Ourari Malika , Ainouche Abdelkader , Coriton Olivier , Huteau Virginie , Brown Spencer , Misset Marie-Thérèse , Ainouche Malika , Amirouche Rachid
Published: August 2011

Population diversity and evolutionary relationships in the Hordeum murinum L. polyploid complex were explored in contrasted bioclimatic conditions from Algeria. A multidisciplinary approach based on morphological, cytogenetic, and molecular data was conducted on a large population sampling. Distribution of diploids (subsp. glaucum) and tetraploids (subsp. leporinum) revealed a strong correlation with a North–South aridity gradient. Most cytotypes exhibit regular meiosis with variable irregularities in some tetraploid populations. Morphological analyses indicate no differentiation among taxa but high variability correlated with bioclimatic parameters. Two and three different nuclear sequences (gene coding for an unspliced genomic protein kinase domain) were isolated in tetraploid and hexaploid cytotypes, respectively, among which one was identical with that found in the diploid subsp. glaucum. The tetraploids (subsp. leporinum and subsp. murinum) do not exhibit additivity for 5S and 45S rDNA loci comparative with the number observed in the related diploid (subsp. glaucum). The subgenomes in the tetraploid taxa could not be differentiated using genomic in situ hybridization (GISH). Results support an allotetraploid origin for subsp. leporinum and subsp. murinum that derives from the diploid subsp. glaucum and another unidentified diploid parent. The hexaploid (subsp. leporinum) has an allohexaploid origin involving the two genomes present in the allotetraploids and another unidentified third diploid progenitor.
VERTEX OPERATOR ALGEBRAS AND WEAK JACOBI FORMS
Authors: KRAUEL MATTHEW , MASON GEOFFREY
Published: August 2011

Let V be a strongly regular vertex operator algebra. For a state h ∈ V1 satisfying appropriate integrality conditions, we prove that the space spanned by the trace functions Tr M qL(0)-c/24ζh(0) (M a V-module) is a vector-valued weak Jacobi form of weight 0 and a certain index 〈h, h〉/2. We discuss refinements and applications of this result when V is holomorphic, in particular we prove that if g = eh(0) is a finite-order automorphism then Tr V qL(0)-c/24g is a modular function of weight 0 on a congruence subgroup of SL 2(ℤ).
APPROXIMATIONS OF SOBOLEV NORMS IN CARNOT GROUPS
Authors: BARBIERI DAVIDE
Published: August 2011

This paper deals with a notion of Sobolev space W1, pintroduced by Bourgain, Brezis and Mironescu by means of a seminorm involving local averages of finite differences. This seminorm was subsequently used by Ponce to obtain a Poincaré-type inequality. The main results that we present are a generalization of these two works to a non-Euclidean setting, namely that of Carnot groups. We show that the seminorm expressed in terms of the intrinsic distance is equivalent to the Lp-norm of the intrinsic gradient, and provide a Poincaré-type inequality on Carnot groups by means of a constructive approach which relies on one-dimensional estimates. Self-improving properties are also studied for some cases of interest.
BREZIS–MERLE INEQUALITIES AND APPLICATION TO THE GLOBAL EXISTENCE OF THE CAUCHY PROBLEM OF THE KELLER–SEGEL SYSTEM
Authors: NAGAI TOSHITAKA , OGAWA TAKAYOSHI
Published: August 2011

We discuss the existence of the global solution for two types of nonlinear parabolic systems called the Keller–Segel equation and attractive drift–diffusion equation in two space dimensions. We show that the system admits a unique global solution in [Formula: see text]. The proof is based upon the Brezis–Merle type inequalities of the elliptic and parabolic equations. The proof can be applied to the Cauchy problem which is describing the self-interacting system.
COMBINATORIAL YAMABE FLOW ON HYPERBOLIC SURFACES WITH BOUNDARY
Authors: GUO REN
Published: August 2011

This paper studies the combinatorial Yamabe flow on hyperbolic surfaces with boundary. It is proved by applying a variational principle that the length of boundary components is uniquely determined by the combinatorial conformal factor. The combinatorial Yamabe flow is a gradient flow of a concave function. The long-time behavior of the flow and the geometric meaning is investigated.
MULTIPLE BOUNDED VARIATION SOLUTIONS OF A PERIODICALLY PERTURBED SINE-CURVATURE EQUATION
Authors: OBERSNEL FRANCO , OMARI PIERPAOLO
Published: August 2011

We prove the existence of at least two T-periodic solutions, not differing from each other by an integer multiple of 2π, of the sine-curvature equation [Formula: see text] We assume that A ∈ ℝ and [Formula: see text] is a T-periodic function such that [Formula: see text] and, e.g. ‖h‖L∞< 4/T. Our approach is variational and makes use of basic results of non-smooth critical point theory in the space of bounded variation functions.
AN ANISOTROPIC INFINITY LAPLACIAN OBTAINED AS THE LIMIT OF THE ANISOTROPIC (p, q)-LAPLACIAN
Authors: PEREZ-LLANOS MAYTE , ROSS JULIO D.
Published: August 2011

In this work we study the behavior of the solutions to the following Dirichlet problem related to the anisotropic (p, q)-Laplacian operator [Formula: see text] as p, q → ∞. Here Ω ⊂ ℝN× ℝKand [Formula: see text] and [Formula: see text] denote the gradient of u with respect to the first N variables (x variables) and with respect to the last K variables (y variables). We consider a sequence of exponents (pn, qn) that goes to infinity with pn/qn→ R. We prove that un, the solution with p = pn, q = qn, verifies un→ u∞uniformly in [Formula: see text], where u∞is the unique viscosity solution to [Formula: see text] Here [Formula: see text] and [Formula: see text] are the infinity Laplacian in x variables and in y variables, respectively.
ASYMPTOTIC AXISYMMETRY OF THE SUBSONIC TRAVELING WAVES TO THE GROSS–PITAEVSKII EQUATION
Authors: WEI JUNCHENG , YAO WEI
Published: August 2011

In this paper we show the asymptotic axisymmetry of subsonic traveling waves of finite energy to the Gross–Pitaevskii equation. In particular, using a new Hamiltonian identity, we prove that the momentum in the orthogonal directions must vanish.
THE POST-BUCKLED BEHAVIOR IN THIN-WALLED CONSTRUCTION AND ITS PARTIAL "EROSION" UNDER REPEATED LOADING
Authors: ŠKALOUD MIROSLAV , ZÖRNEROVÁ MARIE
Published: August 2011

There are two ways to make steel construction more competitive: (i) to save steel (via thin-walled structures) and (ii) to save fabrication costs (via economic-fabrication structures). The authors' studies on post-buckled behavior in thin-walled construction and its partial "erosion" under many times repeated loading are described. S–N curves are established by the authors based on their numerous tests, such as to be used in the design of webs breathing under repeated loading. A reduction of some fabrication procedures as a way to economic-fabrication construction is discused, e.g. the possibility to avoid straightening of plate elements involved. Formulae for a user-friendly design of the webs of economic-fabrication steel girders, such as to make it possible to disregard their breathing, are also presented.
GLOBAL IMPERFECTIONS AND DIMENSIONAL VARIATIONS IN COLD-FORMED STEEL MEMBERS
Authors: ZEINODDINI VAHID , SCHAFER BENJAMIN W.
Published: August 2011

The objective of this paper is to provide the results from an experimental program to measure global imperfections and dimensional variations in cold-formed steel-lipped channel members. Measurements were conducted at seven different manufacturing plants in the United States. A total of 210 cross sections were measured for global imperfections. Each cross section was measured at three locations, and every 305 mm (12 in.) along the length. The data is used to characterize global bow, camber, and twist. The majority of the data exhibits global imperfections well approximated by a half sine-wave. Further, global bow imperfections are shown to have a systematic bias in the direction of bow. The measured data is compared with manufacturing tolerances (e.g., L/384) and assumed imperfection sizes from column curves (e.g., L/960) as utilized in design practice in the United States. The measured imperfections served as justification for tightening manufacturing tolerances in the United States (e.g., to L/960). Dimensional variation of typical cold-formed steel members is also measured and compared with tolerances. The measured data provides much needed input for nonlinear analysis of cold-formed steel structures.
STABILITY BEHAVIOR AND DESIGN OF NONCONVENTIONAL COLD-FORMED STEEL STRUCTURES — RESEARCH REVIEW
Authors: DUNAI LÁSZLÓ , JAKAB GÁBOR
Published: August 2011

In the paper, the methodology and main results of two research projects on nonconventional cold-formed thin-walled steel structures are presented. Laboratory tests, standard-based calculations, numerical models, and the connection of these to design method development are summarized. The implementation of the methodology is presented on two areas in detail: CompressionC-section members and a truss made of C-section members.

The studied CompressionC-section members are of various cross-sectional arrangement and end- and lateral-supporting conditions. They consist of single or double asymmetric C-section members; in the latter case, either a back-to-back arrangement is applied or two sections are stuck in each other, forming a box-like closed section. The applied load is in each case compression with different eccentricities. Test arrangement, program, and results are presented; measured load-bearing capacities are compared to resistances calculated according to Eurocode 3, Part 1–3 where applicable, design rules for the cases not covered by the code are proposed.

Trusses made of C-sections from the same product line are analyzed in the light of full-scale laboratory tests. EC3-based design formulae are derived for the failure modes obtained in the tests either by modifying existing application rules or by deriving new ones from these.

Advanced numerical models of both structures are presented with focus on modeling imperfections, bolted connections, and joint rigidities.
GEOMETRICALLY NONLINEAR ANALYSIS OF STEEL STORAGE RACKS SUBMITTED TO EARTHQUAKE LOADING
Authors: DEGEE HERVE , ROSSI BARBARA , JEHIN DENIS
Published: August 2011

Steel storage racks are light and flexible structures. When submitted to earthquake loading, they can exhibit very large transverse displacements and are thus prone to significant consequences of second-order geometrical effects. In the context of the drafting of European recommendations for the design of steel pallet racks for their seismic resistance, this paper presents a parameter study comparing the various methods commonly used in practice for analyzing the seismic structural behavior of racks (i.e. "modal response spectrum analysis" and "lateral force method analysis") as well as the different ways to account for geometrically nonlinear effects in these conventional methods of analysis in the case of structures designed for low ductility.
Hyaluronan in intestinal homeostasis and inflammation: implications for fibrosis
Authors: de la Motte Carol A.
Published: August 2011

The causes of fibrosis, or the inappropriate wound healing, that follows chronic intestinal inflammation are not well defined and likely involve the contributions of multiple cellular mechanisms. As other articles in this series confirm, inflammatory cytokines clearly play a role in driving cell differentiation to the myofibroblast phenotype, promoting proliferation and extracellular matrix deposition that are characteristic of fibrotic tissue. However, controlling the balance of cytokines produced and process of myofibroblast differentiation appears to be more complex. This review considers ways in which hyaluronan, an extracellular matrix component that is remodeled during the progression of colitis, may provide indirect as well as direct cues that influence the balancing act of intestinal wound healing.
Menin and JunD regulate gastrin gene expression through proximal DNA elements
Authors: Mensah-Osman Edith J. , Veniaminova Natalia A. , Merchant Juanita L.
Published: August 2011

Mutations in the MEN1 gene correlate with multiple endocrine neoplasia I (MEN1). Gastrinomas are the most malignant of the neuroendocrine tumors associated with MEN1. Because menin and JunD proteins interact, we examined whether JunD binds to and regulates the gastrin gene promoter. Both menin and JunD are ubiquitous nuclear proteins that we showed colocalize in the gastrin-expressing G cells of the mouse antrum. Transfection with a JunD expression vector alone induced endogenous gastrin mRNA in AGS human gastric cells, and the induction was blocked by menin overexpression. We mapped repression by menin to both a nonconsensus AP-1 site and proximal GC-rich elements within the human gastrin promoter. Chromatin immunoprecipitation assays, EMSAs, and DNA affinity precipitation assays documented that JunD and Sp1 proteins bind these two elements and are both targets for menin regulation. Consistent with menin forming a complex with histone deacetylases, we found that repression of gastrin gene expression by menin was reversed by trichostatin A. In conclusion, proximal DNA elements within the human gastrin gene promoter mediate interactions between JunD, which induces gastrin gene expression and menin, which suppresses JunD-mediated activation.
Atorvastatin treatment reduces exercise capacities in rats: involvement of mitochondrial impairments and oxidative stress
Authors: Bouitbir Jamal , Charles Anne-Laure , Rasseneur Laurence , Dufour Stéphane , Piquard François , Geny Bernard , Zoll Joffrey
Published: August 2011

Physical exercise exacerbates the cytotoxic effects of statins in skeletal muscle. Mitochondrial impairments may play an important role in the development of muscular symptoms following statin treatment. Our objective was to characterize mitochondrial function and reactive oxygen species (ROS) production in skeletal muscle after exhaustive exercise in atorvastatin-treated rats. The animals were divided into four groups: resting control (CONT; n = 8) and exercise rats (CONT+EXE; n = 8) as well as resting (ATO; n = 10) and exercise (ATO+EXE; n = 8) rats that were treated with atorvastatin (10 mg·kg−1·day−1for 2 wk). Exhaustive exercise showed that the distance that was covered by treated animals was reduced ( P < 0.05). Using dihydroethidium staining, we showed that the ROS level was increased by 60% in the plantaris muscle of ATO compared with CONT rats and was highly increased in ATO+EXE (226%) compared with that in CONT+EXE rats. The maximal mitochondrial respiration (Vmax) was decreased in ATO rats compared with that in CONT rats ( P < 0.01). In CONT+EXE rats, Vmaxsignificantly increased compared with those in CONT rats ( P < 0.05). Vmaxwas significantly lower in ATO+EXE rats (−39%) compared with that in CONT+EXE rats ( P < 0.001). The distance that was covered by rats significantly correlated with Vmax( r = 0.62, P < 0.01). The glycogen content was decreased in ATO, CONT+EXE, and ATO+EXE rats compared with that in CONT rats ( P < 0.05). GLUT-4 mRNA expression was higher after exhaustive exercise in CONT+EXE rats compared with the other groups ( P < 0.05). Our results show that exhaustive exercise exacerbated metabolic perturbations and ROS production in skeletal muscle, which may reduce the exercise capacity and promote the muscular symptoms in sedentary atorvastatin-treated animals.