bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling relationships: Hospital occupancy levels, discharge timing and emergency department access block
Authors: Khanna Sankalp , Boyle Justin , Good Norm , Lind James
Published: August 2012

Objectives

To investigate the effect of hospital occupancy levels on inpatient and ED patient flow parameters, and to simulate the impact of shifting discharge timing on occupancy levels.

Methods

Retrospective analysis of hospital inpatient data and ED data from 23 reporting public hospitals in Queensland, Australia, across 30 months. Relationships between outcome measures were explored through the aggregation of the historic data into 21 912 hourly intervals. Main outcome measures included admission and discharge rates, occupancy levels, length of stay for admitted and emergency patients, and the occurrence of access block. The impact of shifting discharge timing on occupancy levels was quantified using observed and simulated data.

Results

The study identified three stages of system performance decline, or choke points, as hospital occupancy increased. These choke points were found to be dependent on hospital size, and reflect a system change from ‘business‐as‐usual’ to ‘crisis’. Effecting early discharge of patients was also found to significantly (P < 0.001) impact overcrowding levels and improve patient flow.

Conclusions

Modern hospital systems have the ability to operate efficiently above an often‐prescribed 85% occupancy level, with optimal levels varying across hospitals of different size. Operating over these optimal levels leads to performance deterioration defined around occupancy choke points. Understanding these choke points and designing strategies around alleviating these flow bottlenecks would improve capacity management, reduce access block and improve patient outcomes. Effecting early discharge also helps alleviate overcrowding and related stress on the system.
Various infection status and molecular evidence for horizontal transmission and recombination of Wolbachia and Cardinium among rice planthoppers and related species
Authors: Zhang Kai‐Jun , Han Xiao , Hong Xiao‐Yue
Published: August 2012

Wolbachia and Cardinium are widely distributed and are considered important for their ability to disturb reproduction and affect other fitness‐related traits of their hosts. By using multilocus sequence typing (MLST), RFLP (restriction fragment length polymorphism) and 16S ribosomal DNA gene sequencing methods, we extensively surveyed Wolbachia and Cardinium infection status of four predominant rice planthoppers and one kind of leafhopper in different rice fields. The results demonstrated that Sogatella furcifera (Horváth) and Laodelphax striatellus (Fallén) were infected with the same Wolbachia strain (wStri), while Nilaparvata lugens (Stål) and its closely related species Nilaparvata muiri China were infected with two phylogeneticlly distant strains, wLug and wMui, respectively. Three new Wolbachia strains (provisionally named wMfas1, wMfas2 and wMfas3) were detected in the leafhopper Macrosteles fascifrons (Stål). Only S. furcifera was co‐infected with Cardinium, which indicated that the distribution of Cardinium in these rice planthoppers was narrower than that of Wolbachia. Unambiguous intragenic recombination events among these Wolbachia strains and incongruent phylogenetic relationships show that the connections between different Wolbachia strains and hosts were more complex than we expected. These results suggest that horizontal transmission and host associated specialization are two factors affecting Wolbachia and Cardinium infections among planthoppers and their related species.
Effects of Tomato Powder on Color, Lipid Oxidation and Sensory Properties of Comminuted Meat Products
Authors: Modzelewska‐Kapituła Monika
Published: August 2012

The objective of the study was to investigate the effects of commercially available tomato powder (TP) (Altoma 9010, Diana Naturals, Antrain, France) on production yield, cooking loss, acidity, color, lipid oxidation and sensory properties of meatloaf, and to determine the optimal level of TP addition. Six batches of meatloaves were produced: with 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0% TP. The addition of TP did not affect the production yield and cooking loss of the products. The batters, in which higher amount than 0.4% of TP was used, had pH values significantly lower as compared to the control (
P < 0.05). The addition of TP did not affect lightness (L*) of products but it increased redness (a*), yellowness (b*), hue and saturation index. All meatloaves gained high scores (4 and above on the 1–5 scale) for all sensory attributes, which indicates their good sensory quality. The addition of TP did not retard lipid oxidation in meatloaves, but actually promoted it in the products containing 1.0% TP. Based on the factors that are most important to the meat processors (pH value, production yield, sensory quality), the recommended level of TP addition is 0.4–0.8%.

Practical Applications

This study will inform producers on the possibilities to manufacture comminuted meat products with the addition of tomato powder as a lycopene source. Moreover, it indicates a consumer preference for comminuted meat products containing tomato powder, as well as the influence of the additive on acidity, lipid oxidation and color of the products. As far as commercial tomato powders differ in terms of chemical composition, including lycopene concentration, their influence on product quality is also diverse. The results of the study will help producers to design their new meat products with tomato powder, which has the same or similar chemical characteristics as used in the study.
Mortality and Causes of Death in the Familial Intracranial Aneurysm Study
Authors: Sauerbeck Laura , Hornung Richard , Woo Daniel , Moomaw Charles J. , Anderson Craig , Connolly E. Sander , Rouleau Guy A. , Brown Robert D. , Broderick Joseph P. ,   the FIA Study Investigators
Published: August 2012

Background

Higher mortality for patients with aneurysmal subarachnoid haemorrhage has been reported.

Aims

In families with intracranial aneurysms, we sought to determine whether mortality among subjects with intracranial aneurysm (affected) was higher and related to rupture, compared with unaffected family members.

Methods

Subjects enrolled in the Familial Intracranial Aneurysm protocol were contacted yearly and their status was obtained. If reported to be deceased, the cause of death was verified by available records. A Cox proportional hazards model was utilized to compare mortality rates.

Results

Of the 2794 subjects, 1073 were affected and 1721 were unaffected. There were 8525 person-years of follow-up (mean 3·05 ± 1·73 years) and 85 deaths. Age at study entry for the affected (58·4 ±11·9 years) was significantly older ( P < 0·0001) than for the unaffected (52·2 ± 16·1). After adjusting for age, the overall mortality rate for the affected subjects was not significantly different from that for the unaffected (Rate Ratio [RR] 1·26, 95% confidence interval 0·82–1·93, P = 0·292). There was a strong effect modification due to age. The mortality rate ratio of the affected to the unaffected who were ≤60 years of age was RR = 3·48 (95% confidence interval: 1·59–7·63, P = 0·002), the rate for the affected subjects who were ≥60 was less than the rate for the unaffected (RR = 0·69, 95% confidence interval: 0·404–1·19, P = 0·178). The affected who had ruptures had 2·62 times the mortality rate as those without ruptures (95% confidence interval 1·43–4·80, P = 0·002).

Conclusion

The overall mortality was similar for the affected and unaffected subjects in this cohort. Among the affected only, those with ruptured intracranial aneurysm had a higher mortality rate than those without ruptured.
Comparison of Quantitative Estimation of Intracerebral Hemorrhage and Infarct Volumes after Thromboembolism in an Embolic Stroke Model
Authors: Eriksen Nina , Rasmussen Rune S. , Overgaard Karsten , Johansen Flemming F. , Pakkenberg Bente
Published: August 2012

Background

Strokes have both ischemic and hemorrhagic components, but most studies of experimental stroke only address the ischemic component. This is likely because investigations of hemorrhagic transformation are hindered by the lack of methods based on unbiased principles for volume estimation.

Aims

We evaluated different methods for estimating the volume of infarcts, hemorrhages, after embolic middle cerebral artery occlusion with or without thrombolysis.

Methods

An experimental thromboembolytic rat model was used in this study. The rats underwent surgery and were placed in two groups. Group 1 was treated with saline, and group 2 was treated with 20 mg/kg recombinant tissue plasminogen activator to promote intracerebral hemorrhages. Stereology, semiautomated computer estimation, and manual erythrocyte counting were used to test the precision and efficiency of determining the size of the infarct and intracerebral hemorrhage.

Results

No differences were observed in the infarct volume or amount of bleeding when comparing the three methods of volume estimation. Although semiautomated computer estimation and manual erythrocyte counting provided similar results as the stereological measurements, the stereological method was the most efficient and advantageous.

Conclusions

We found that stereology was the superior method for quantification of hemorrhagic volume, especially for rodent petechial bleeding, which is otherwise difficult to measure. Our results suggest the possibility of measuring both the ischemic and the hemorrhagic components of stroke, two parameters that may be differentially regulated when therapeutic regimens are tested.
Prediction of Vascular Risk after Stroke — Protocol and Pilot Data of the Prospective Cohort with Incident Stroke (PROSCIS)
Authors: Liman Thomas G. , Zietemann Vera , Wiedmann Silke , Jungehuelsing Gerhard J. , Endres Matthias , Wollenweber Frank A. , Wellwood Ian , Dichgans Martin , Heuschmann Peter U.
Published: August 2012

Rationale

Long-term risk of vascular disease is substantially increased after stroke with several models proposed to predict subsequent stroke and other vascular events after an index event. However, recent validation studies demonstrate limited predictive properties of available prognostic models.

Aims

We aim to determine prediction models of different complexity for the combined vascular end-point of stroke, myocardial infarction, and vascular death at three-years after first-ever stroke. An independent external validation of the developed models will be performed.

Design

Prospective observational hospital-based cohort study of patients after first-ever stroke.

Methods

The new predictive models will be developed using the following steps: ( 1 ) Development of a basic score based on clinical history data (e.g. hypertension, myocardial infarction, and atrial fibrillation); ( 2 ) Development of an advanced score including additional factors such as blood-based biomarkers and results of vascular imaging; ( 3 ) Comparing the models fit using different methods (discrimination, calibration); ( 4 ) Assessment of clinical utility of an advanced score using methods based on reclassification tables (e.g. net reclassification improvement, integrated discrimination improvement, decision curve analysis); and ( 5 ) Investigation of external validity.

Outcomes

Primary outcome is a combined vascular end-point composed of stroke, myocardial infarction, and vascular death at three-years after stroke. Furthermore, each component of the composite end-point will be investigated individually and the patterns and time points of risk transitions between vascular end-points and stroke sub-types will be determined.
Validation of the Totaled Health Risks in Vascular Events (THRIVE) Score for Outcome Prediction in Endovascular Stroke Treatment
Authors: Flint Alexander C. , Kamel Hooman , Rao Vivek A. , Cullen Sean P. , Faigeles Bonnie S. , Smith Wade S.
Published: August 2012

Background

We recently developed the Totaled Health Risks In Vascular Events (THRIVE) score to predict outcomes after endovascular stroke treatment. The THRIVE score, which incorporates age, National Institutes of Health Stroke Scale score, and three medical comorbidities (hypertension, diabetes mellitus, and atrial fibrillation), was developed using data from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials.

Aims

We set out to perform external validation of the THRIVE score using data from the largest registry of endovascular stroke treatment performed to date, the Merci Registry.

Methods

We compared the performance of the THRIVE score in two different data sets: the development cohort (the MERCI and Multi MERCI trials, n = 305) and a validation cohort (the Merci Registry, a prospective multicenter registry of patients undergoing endovascular stroke treatment, n = 1000). We examined the predictive utility of the THRIVE score across the range of clinical outcomes and used receiver–operator characteristics curve analysis to compare score performance in the two data sets.

Results

The THRIVE score predicted good outcome, death, and the full range of the modified Rankin Scale in a similar fashion between the MERCI trials and the Merci Registry. Receiver–operator characteristics curve comparisons showed no statistically significant difference in the performance of the THRIVE score between the two data sets: for good outcome, the receiver–operator characteristics area under the curve was 0.293 for the MERCI trials and 0.266 for the Merci Registry ( P = 0.47) and for death, the receiver–operator characteristics area under the curve was 0.692 for the MERCI trials and 0.717 for the Merci Registry ( P = 0.48). The THRIVE score and vessel recanalization were also found to be independent and unrelated predictors of clinical outcome.

Conclusions

The THRIVE score reliably predicts outcomes after endovascular stroke treatment and may be useful as a clinical prognostic tool and to perform severity adjustments in stroke clinical research.
Adaptation of the Natural Resources Conservation Service (NRCS) curve number (CN) model in estimating direct run‐off from humid tropical forest catchments
Authors: Mware Mugo , Mwasi Benjamin , Mburu Francis , Sirma Peter , Koech Eric
Published: August 2012

Suitability of the Natural Resources Conservation Service (NRCS) curve number (CN) model of run‐off prediction was evaluated on three humid tropical forested catchments in Kimakia, Kenya. The catchments were dominated by Pinus patula (catchment A), Arundinaria alpina (catchment C) and Pennisetum clandestinum (catchment M). The study used discharge and rainfall data collected between 1958 and 1986. Seventy‐three (73) isolated storms were graphically separated into baseflow, interflow and surface run‐off. Forest cover types significantly improved catchments characteristics that influence baseflow and interflow generation in catchment C but not those that influence surface run‐off production. In its original form, the NRCS CN model resulted in direct run‐off estimates that deviated from observed ones by between 43.8% and 55.3%. These discrepancies were minimized through modification of the β and CN parameters. CN generated empirically using storm rainfall predicted the direct run‐off satisfactorily. Therefore, the modified NRCS CN model adequately estimates direct run‐off from humid tropical forested catchments.
Detection of pathogenic Escherichia coli strains in groundwater in the Yaoundé region (Cameroon, Central Africa)
Authors: Nola Moïse , Nougang Mireille E. , Noah Ewoti Olive V. , Moungang Luciane M. , Krier François , Chihib Nour‐Eddine
Published: August 2012

This study was aimed at assessing the prevalence of pathogenic Escherichia coli strains, relative to the total count of E. coli, faecal coliforms and other heterotrophic mesophilic aerobic bacteria (HMAB) isolated in groundwater in the equatorial region of Cameroon (Central Africa). Bacteria were isolated using standard methods. Pathogenic E. coli strains were then identified using haemagglutination and antisera tests. The maximum abundance of HMAB, faecal coliforms and E. coli strains were 4.9 × 106, 5.6 × 103 and 1 × 103 colony‐forming units (CFU)/100 mL, respectively. The count of pathogenic E. coli strains reached 3 CFU/100 mL. The counts of commensal and pathogenic E. coli strains underwent temporal and spatial fluctuations. In 21% of sampling sites, the abundance of faecal coliforms was significantly correlated to that of E. coli (P < 0.05). However, the isolated bacterial count was not significantly correlated to that of the pathogenic E. coli strains (P > 0.05). The bacteria abundance dynamics may be impacted by many interacting factors.
Anti-inflammatory effect of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol, a new derivative of 4-nerolidylcatechol
Authors: Lino Roberta Campos , Martins Fabiula Ines , Florentino Iziara Ferreira , Nascimento Marcus Vinicius Mariano , Galdino Pablinny Moreira , Andrade Carolina H , Rezende Kênnia Rocha , Menegatti Ricardo , Costa Elson Alves
Published: August 2012

Objectives

We have investigated the anti-inflammatory and antinociceptive effects of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol (LQFM-015), which was designed through molecular simplification strategy from 4-nerolidylcatechol.

Methods

The possible anti-inflammatory and antinociceptive effects were assayed on carrageenan-induced paw oedema and pleurisy, acetic acid-induced abdominal writhing and formalin tests in mice.

Key findings

LQFM-015 reduced the activity of PLA2 enzyme in vitro by 18%. Docking studies into the catalytic site of PLA2 were used to identify the binding mode of the LQFM-015. LQFM-015 showed a moderate antinociceptive effect, since this compound reduced the number of writhings by approximately up to 40% in the acetic acid-induced pain model; this antinociceptive activity also emerged in the second phase of the formalin-induced pain model (58% of inhibition). The anti-inflammatory action of LQFM-015 was confirmed in acute inflammation models, in which it reduced the formation of oedema to 52.78 ± 8.6 and 46.64 ± 5.2 at the second and third hour of carrageenan-induced paw oedema, respectively. Also in the carrageenan-induced pleurisy model, LQFM-015 reduced the migration of leucocytes by 26.0% and decrease myeloperoxidase activity by 50%. LQFM-015 showed different concentrations to inhibit 50% of isoenzyme cyclooxygenase activity (IC50); COX-1 IC50 = 36 μm) and COX-2 IC50 = 28 μm.

Conclusions

LQFM-015 demonstrated inhibition of both PLA2 and COX enzymes; thus, the moderate antinociceptive effect of this compound could be attributed to its anti-inflammatory activity.
Enhanced evaluation of selective androgen receptor modulators in vivo
Authors: Otto‐Duessel M. , He M. , Adamson T. W. , Jones J. O.
Published: August 2012

Selective androgen receptor modulators (SARMs) are a class of drugs that control the activity of the androgen receptor (AR), which mediates the response to androgens, in a tissue‐selective fashion. They are specifically designed to reduce the possible complications that result from the systemic inhibition or activation of AR in patients with diseases that involve androgen signalling. However, there are no ideal in vivo models for evaluating candidate SARMs. Therefore, we created a panel of androgen‐responsive genes in clinically relevant AR expressing tissues including prostate, skin, bone, fat, muscle, brain and kidney. We used select genes from this panel to compare transcriptional changes in response to the full agonist dihydrotestosterone (DHT) and the SARM bolandiol at 16 h and 6 weeks. We identified several genes in each tissue whose expression at each of these time points correlates with the known tissue‐specific effects of these compounds. For example, in the prostate we found four genes whose expression was much lower in animals treated with bolandiol compared with animals treated with DHT for 6 weeks, which correlated well with differences in prostate weight. We demonstrate that adding molecular measurements (androgen‐regulated gene expression) to the traditional physiological measurements (tissue weights, etc.) makes the evaluation of potential SARMs more accurate, thorough and perhaps more rapid by allowing measurement of selectivity after only 16 h of drug treatment.
Acute Termination of Human Atrial Fibrillation by Identification and Catheter Ablation of Localized Rotors and Sources: First Multicenter Experience of Focal Impulse and Rotor Modulation (FIRM) Ablation
Authors: SHIVKUMAR KALYANAM , ELLENBOGEN KENNETH A. , HUMMEL JOHN D. , MILLER JOHN M. , STEINBERG JONATHAN S.
Published: August 2012

FIRM Ablation of Human AF Rotors. Introduction: Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets.

Methods:
We prospectively enrolled the first (n = 14, 11 males) consecutive patients undergoing FIRM‐guided ablation for persistent (n = 11) and paroxysmal AF at 5 centers. A 64‐pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10% cycle length prolongation). Conventional ablation was performed only after FIRM‐guided ablation.

Results:
Twelve out of 14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9 ± 0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM‐guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n = 8 (4.9 ± 3.9 minutes at the primary source), and organization in n = 4. Total FIRM time for all patients was 12.3 ± 8.6 minutes.

Conclusions:
FIRM‐guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM‐guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1277‐1285, December 2012)
Anatomical Predictors for Acute and Mid‐Term Success of Cryoballoon Ablation of Atrial Fibrillation Using the 28 mm Balloon
Authors: KNECHT SVEN , KÜHNE MICHAEL , ALTMANN DAVID , AMMANN PETER , SCHAER BEAT , OSSWALD STEFAN , STICHERLING CHRISTIAN
Published: August 2012

Anatomical Predictors for Acute and Mid‐Term Success of Cryoballoon Ablation. Introduction: Cryoballoon (CB) pulmonary vein isolation (CB‐PVI) for the treatment of paroxysmal atrial fibrillation (AF) has been demonstrated to be safe and reliable. Preprocedural patient selection to address the high variability in pulmonary vein (PV) anatomy may improve the acute and chronic success of CB‐PVI. The purpose of this study was to identify anatomical predictors for CB‐PVI failure using the 28 mm balloon.

Methods and Results
: We included 47 patients with paroxysmal AF undergoing CB‐PVI with the 28 mm CB. Anatomical global left atrial and PV selective parameters were quantified from 3‐dimensional reconstructed preprocedural computed tomography or magnetic resonance imaging data. The mean follow‐up was 26 ± 9 months (range: 12–32 months). Multivariate logistic regression analysis revealed that a continuous sharp left lateral ridge between the left PVs and the left lateral appendage (OR, 7.09; 95% CI, 1.17–43.47) and a sharp carina between the left superior and left inferior PV (OR, 5.99; 95% CI, 1.33–27.03) predict acute and mid‐term failure. For the right inferior PVs, a non‐perpendicular angle between the axis of the PV and the ostial plane (OR, 6.33; 95% CI, 1.20–33.33) and an early branching PV with change in the axis angle (OR, 7.41; 95% CI, 1.44–38.46) were predictors of acute and mid‐term failure.

Conclusion:
Anatomical variables preventing maximal heat transfer from the tissue to the CB could be identified as predictors for CB‐PVI failure with the 28 mm balloon. These findings may be a step toward a more tailored ablation strategy based on individual anatomical variations. (J Cardiovasc Electrophysiol, Vol. 24, pp. 132‐138, February 2013)
Adenosine receptor stimulation by polynucleotides (PDRN) reduces inflammation in experimental periodontitis
Authors: Bitto Alessandra , Oteri Giacomo , Pisano Michele , Polito Francesca , Irrera Natasha , Minutoli Letteria , Squadrito Francesco , Altavilla Domenica
Published: August 2012

Aim

Adenosine receptors modulate inflammation in periodontal tissues. No data are available regarding the effects of adenosine A2A receptor stimulation in experimental periodontitis (EPD). The aim of this study was to investigate the effects of polynucleotides (also known as polydeoxyribonucleotide, PDRN), a ligand of A2A receptor, in EPD in rats.

Materials and Methods

EPD was induced ligating the cervix of the lower left first molar. Sham‐EPD had no ligature. After 7 days, EPD animals were randomized to a daily treatment with vehicle gel or 0.75% PDRN gel or PDRN gel with a specific A2A antagonist (DMPX). Treatments lasted 7 days. Animals were then euthanized and the periodontium and surrounding gingival tissue were excised for histological evaluation and bio‐molecular analysis of inflammatory (p‐JNK, p‐ERK, TNF‐α, IL‐6, HMGB‐1) and apoptotic proteins (BAX and Bcl‐2).

Results

Vehicle‐treated EPD rats showed severe inflammatory infiltrate in both gingival and periodontal ligament, as well as an enhanced expression of p‐JNK, p‐ERK, TNF‐α, IL‐6, HMGB‐1 and BAX and a reduction in Bcl‐2. PDRN gel restored the histological features, blunted inflammatory and apoptotic proteins expression and preserved Bcl‐2 expression. DMPX abrogated PDRN positive effects.

Conclusion

Our data suggest that adenosine receptor stimulation by PDRN might represent a new therapeutic strategy for periodontitis.
Bronchial intubation could be detected by the visual stethoscope techniques in pediatric patients
Authors: Kimura Tetsuro , Suzuki Akira , Mimuro Soichiro , Makino Hiroshi , Sato Shigehito
Published: August 2012

Background

We created a system that allows the visualization of breath sounds (visual stethoscope).

Aim

We compared the visual stethoscope technique with auscultation for the detection of bronchial intubation in pediatric patients.

Methods

In the auscultation group, an anesthesiologist advanced the tracheal tube, while another anesthesiologist auscultated bilateral breath sounds to detect the change and/or disappearance of unilateral breath sounds. In the visualization group, the stethoscope was used to detect changes in breath sounds and/or disappearance of unilateral breath sounds. The distance from the edge of the mouth to the carina was measured using a fiberoptic bronchoscope.

Results

Forty pediatric patients were enrolled in the study. At the point at which irregular breath sounds were auscultated, the tracheal tube was located at 0.5 ± 0.8 cm on the bronchial side from the carina. When a detectable change of shape of the visualized breath sound was observed, the tracheal tube was located 0.1 ± 1.2 cm on the bronchial side (not significant). At the point at which unilateral breath sounds were auscultated or a unilateral shape of the visualized breath sound was observed, the tracheal tube was 1.5 ± 0.8 or 1.2 ± 1.0 cm on the bronchial side, respectively (not significant).

Conclusions

The visual stethoscope allowed to display the left and the right lung sound simultaneously and detected changes of breath sounds and unilateral breath sound as a tracheal tube was advanced.
Ultrasound detection of guidewires in‐plane during pediatric central venous catheterization
Authors: Kayashima Kenji , Imai Keiko , Sozen Reiko
Published: August 2012

Objective/Aim

To assess the usefulness of longitudinal ultrasound images of guidewires for pediatric central venous catheter (CVC) placement.

Background

To avoid arterial placement of a CVC, it is important to ensure that the guidewires are in the internal jugular vein (IJV) before inserting the dilators. Ultrasound confirmation of the guidewire position may eliminate accidental arterial dilation during CVC cannulation.

Methods

Fifty pediatric patients undergoing general endotracheal anesthesia for cardiovascular surgery were enrolled. The mean ± sd value for age was 14.8 ± 16.8 months; height, 69.1 ± 14.6 cm; and weight, 7.1 ± 3.2 kg. Longitudinal ultrasound images of guidewires in or around the right IJV during pediatric CVC placement were acquired using an L10‐5 MHz probe (TiTAN®; SonoSite Co., Tokyo, Japan), with the neck of the patient fully extended and the head turned 15–30 degree to the left.

Results

In 42 (84%) patients, guidewires were visible in the lumen of the IJV. However, in 8 (16%) patients, guidewires were not visible. Longitudinal imaging of guidewires was achieved with high probability (100%) in children in whom the distance from the clavicle to the angle of the mandible was more than 59 mm, in whom the distance from the clavicle to the puncture site was more than 30 mm, or in children taller than 65 cm. All cannulations were confirmed to be CVCs by chest radiography.

Conclusions

To confirm the insertion of dilators into veins in children, we recommend that longitudinal images of the guidewires should be initially acquired.
Physical exercise reduces cardiac defects in type 2 spinal muscular atrophy‐like mice
Authors: Biondi Olivier , Lopes Philippe , Desseille Céline , Branchu Julien , Chali Farah , Salah Amina Ben , Pariset Claude , Chanoine Christophe , Charbonnier Frédéric
Published: August 2012

Key points

The present study provides evidence that the cardiomyopathy observed in spinal muscular atrophy (SMA) model mice is mainly due to intrinsic cardiac alteration but not to autonomic impairment.

We demonstrated a non‐pathological sympathetic activity on the heart of type 2 SMA‐like mice, which likely counteracts the dramatic alteration of the cardiac function, such as arrhythmia and reduced heart rate.

We demonstrated for the first time that physical exercise partially restores cardiac conduction efficiency, prevents fibrosis, attenuates defects in protein expression, bradycardia and arrhythmias leading to the partial recovery of heart and respiratory rates in exercised SMA‐like mice.

This study indicates a profound involvement of cellular, structural and vascular cardiac dysfunction in the pathogenesis of SMA, widely opening alternative pharmacological and non‐pharmacological therapeutic strategies that would most certainly include physical exercise.

Abstract  Spinal muscular atrophy (SMA), the leading genetic cause of death in infants worldwide, is due to the misexpression of the survival of motor neuron protein, causing death of motor neurons. Several clinical symptoms suggested that, in addition to motor neurons, the autonomic nervous systems could be implicated in the cardiac function alterations observed in patienst with SMA. These alterations were also found in a severe SMA mouse model, including bradycardia and a reduction of sympathetic innervation, both associated with autonomic imbalance. In the present study, we investigate the extent of autonomic dysfunction and the effects of a running‐based exercise on the altered cardiorespiratory function in type 2 SMA‐like mice. We observed that the SMA induced: (1) a dramatic alteration of intrinsic cardiac conduction associated with bradycardia; (2) a severe cardiomyopathy associated with extensive ventricular fibrosis; and (3) a delay in cardiac muscle maturation associated with contractile protein expression defects. Furthermore, our data indicate that the sympathetic system is not only functioning, but also likely contributes to alleviate the bradycardia and the arrhythmia in SMA‐like mice. Moreover, physical exercise provides many benefits, including the reduction of cardiac protein expression defect, the reduction of fibrosis, the increase in cardiac electrical conduction velocity, and the drastic reduction in bradycardia and arrhythmias resulting in the partial restoration of the cardiac function in these mice. Thus, modulating the cardiorespiratory function in SMA could represent a new target for improving supportive care and for developing new pharmacological and non‐pharmacological interventions that would most certainly include physical exercise.
Homeostatic metaplasticity of corticospinal excitatory and intracortical inhibitory neural circuits in human motor cortex
Authors: Murakami Takenobu , Müller‐Dahlhaus Florian , Lu Ming‐Kuei , Ziemann Ulf
Published: August 2012

Key points

Homeostatic metaplasticity is an important mechanism for maintaining overall synaptic weight of a neuronal network in the physiological range.

Homeostatic metaplasticity has been demonstrated, so far largely exclusively, for excitatory synaptic neurotransmission.

New non‐invasive transcranial magnetic theta burst stimulation (TBS) experiments at the systems level of human motor cortex demonstrate for the first time that homeostatic metaplasticity is also present in inhibitory intracortical circuits.

In addition, manipulation of intracortical inhibition by priming TBS contributes to the homeostatic regulation of metaplasticity in the corticospinal excitatory pathway.

Findings are important for therapeutic applications of non‐invasive brain stimulation that aim at correcting excitatory or inhibitory neurotransmission outside the physiological range in humans with neuropsychiatric disorders.

Abstract  Homeostatic metaplasticity, a fundamental principle for maintaining overall synaptic weight in the physiological range in neuronal networks, was demonstrated at the cellular and systems level predominantly for excitatory synaptic neurotransmission. Although inhibitory networks are crucial for regulating excitability, it is largely unknown to what extent homeostatic metaplasticity of inhibition also exists. Here, we employed intermittent and continuous transcranial magnetic theta burst stimulation (iTBS, cTBS) of the primary motor cortex in healthy subjects for induction of long‐term potentiation (LTP)‐like and long‐term depression (LTD)‐like plasticity. We studied metaplasticity by testing the interactions of priming TBS with LTP/LTD‐like plasticity induced by subsequent test TBS. Changes in excitatory neurotransmission were measured by the input–output curve of motor‐evoked potentials (IO‐MEP), and changes in GABAAergic inhibitory neurotransmission by the IO of short‐interval intracortical inhibition (IO‐SICI, four conditioning stimulus intensities of 70–100% active motor threshold, interstimulus interval 2.0 ms). Non‐primed iTBS increased IO‐MEP, while non‐primed cTBS decreased IO‐MEP. Pairing of identical protocols (iTBS→iTBS, cTBS→cTBS) resulted in suppression of the non‐primed TBS effects on IO‐MEP, and pairing of different protocols (cTBS→iTBS, iTBS→cTBS) enhanced the test TBS effects on IO‐MEP. While non‐primed TBS did not result in significant changes of IO‐SICI, iTBS→iTBS resulted in IO‐SICI decrease, and cTBS→cTBS in IO‐SICI increase compared with the non‐primed conditions. The changes in SICI induced by priming TBS correlated with the changes in MEP induced by subsequent test TBS. Findings demonstrate that plasticity in both excitatory and inhibitory circuits in the human motor cortex are regulated by homeostatic metaplasticity, and that priming effects on inhibition contribute to the homeostatic regulation of metaplasticity in excitatory circuits.
Pull Force and Displacement of Cu/Au Wire Interconnects
Authors: Lau J. , Wu S. , Lau J. M.
Published: August 2012

The pull force and displacement of gold (Au) and copper (Cu) wires in microelectronics are investigated in this study. Emphasis is placed on (1) the development of a set of equations for determining the internal forces and deformations of wires when subjected to an external pull force, (2) the determination of the maximum pull force (when the wire breaks) based on some failure criteria of the wires, and (3) the experimental verification of the present equations.
Inductively coupled plasma deep etching of InP/InGaAsP in Cl2/CH4/H2 based chemistries with the electrode at 20 °C
Authors: Wieczorek Andreas , Djara Vladimir , Peters Frank H. , O’Callaghan James , Thomas Kevin , Corbett Brian
Published: August 2012

A Cl2/CH4/H2 inductively coupled plasma process without additional heating or wafer bonding is developed for the InP/InGaAsP material system. Vertical and smooth sidewalls can be observed in the scanning electron microscope images. The main factors of etch rate, selectivity, and sidewall roughness are analyzed relative to the gas concentration in a full factorial design of the experimental procedure. Under optimized conditions, an etch depth of more than 3 μm with smooth and vertical sidewalls can be obtained. A strong indication of a passivation effect of CH4 is obtained.
Impact of flat panel‐imager veiling glare on scatter‐estimation accuracy and image quality of a commercial on‐board cone‐beam CT imaging system
Authors: Lazos Dimitrios , Williamson Jeffrey F.
Published: August 2012

Purpose:

The purposes of this study is to measure the low frequency drop (LFD) of the modulation transfer function (MTF), associated with the long tails of the detector point spread function (PSF) of an on‐board flat panel imager and study its impact on cone‐beam CT (CBCT) image quality and scatter measurement accuracy.

Methods:

Two different experimental methods were used to characterize LFD and its associated PSF of a Varian OBI flat‐panel detector system: the edge response function (ERF) method and the disk transfer function (DTF) method. PSF was estimated by fitting parametric models to these measurements for four values of the applied voltage (kVp). The resultant PSF was used to demonstrate the effect of LFD on image contrast and CT number accuracy in CBCT images reconstructed from synthetic datasets, as well as, accuracy of scatter measurements with the beam‐stop method.

Results:

The MTFs derived from the measured ERF data revealed LFDs varying from 8% (at 60 kVp) to 10.5% (at 120 kVp), while the intensity of the long PSF tails was found to increase with increasing kVp. The veiling glare line spread functions derived from the ERF and DTF methods were in excellent agreement. Uncorrected veiling glare reduced contrast and the image intensity in CBCT reconstruction, near the phantom periphery (by 67 Hounsfield units in a 20 cm‐in‐diameter water phantom) and (to a smaller degree) near inhomogeneities. Use of the bow‐tie filter mitigated these effects. Veiling glare also resulted in about 10%–15% overestimation of the scatter‐to‐primary ratio when measured with the beam‐stop or beam‐stop array method.

Conclusions:

The long tails of the detector PSF were found to have a modest dependence of beam spectrum, which is reflected on the MTF curve LFD. Our findings show that uncorrected veiling glare can affect quantitative accuracy and contrast in CBCT imaging, based on flat panel imager. In addition, it results in overestimation of the scatter‐to‐primary ratio, measured with the beam‐stop methods.
Comparison of signal to noise ratios from spatial and frequency domain formulations of nonprewhitening model observers in digital mammography
Authors: Sisini Francesco , Zanca Federica , Marshall Nicholas W. , Taibi Angelo , Cardarelli Paolo , Bosmans Hilde
Published: August 2012

Purpose:

Image quality indices based upon model observers are promising alternatives to laborious human readings of contrast‐detail images. This is especially appealing in digital mammography as limiting values for contrast thresholds determine, according to some international protocols, the acceptability of these systems in the radiological practice. The objective of the present study was to compare the signal to noise ratios (SNR) obtained with two nonprewhitening matched filter model observer approaches, one in the spatial domain and the other in the frequency domain, and with both of them worked out for disks as present in the CDMAM phantom.

Methods:

The analysis was performed using images acquired with the Siemens Novation and Inspiration digital mammography systems. The spatial domain formulation uses a series of high dose CDMAM images as the signal and a routine exposure of two flood images to calculate the covariance matrix. The frequency domain approach uses the mathematical description of a disk and modulation transfer function (MTF) and noise power spectrum (NPS) calculated from images.

Results:

For both systems most of the SNR values calculated in the frequency domain were in very good agreement with the SNR values calculated in the spatial domain. Both the formulations in the frequency domain and in the spatial domain show a linear relationship between SNR and the diameter of the CDMAM discs.

Conclusions:

The results suggest that both formulations of the model observer lead to very similar figures of merit. This is a step forward in the adoption of figures of merit based on NPS and MTF for the acceptance testing of mammography systems.
FDA Oversight of Cell Therapy Clinical Trials
Authors: Au Patrick , Hursh Deborah A. , Lim Agnes , Moos Malcolm C. , Oh Steven S. , Schneider Bruce S. , Witten Celia M.
Published: August 2012

U.S. Food and Drug Administration applies regulatory flexibility to balance benefits and risks to subjects in cell-therapy clinical trials.
Author Response to Comment on “Characterization of Circulating Endothelial Cells in Acute Myocardial Infarction”
Authors: Damani Samir , Topol Eric
Published: August 2012

A substantial number of patients with the appropriate clinical phenotypes must be studied to disprove previous findings that circulating endothelial cell counts and morphology can predict atherosclerotic plaque rupture.
Leukocyte Recruitment: Getting on Inflammation’s Nerves
Authors: Yipp Bryan G.
Published: August 2012

The sympathetic nervous system directs circadian oscillations of leukocyte recruitment within local tissue environments.
Residual Antibiotics Disrupt Meat Fermentation and Increase Risk of Infection
Authors: Kjeldgaard Jette , Cohn Marianne T. , Casey Pat G. , Hill Colin , Ingmer Hanne
Published: August 2012

Fermented sausages, although presumed safe for consumption, sometimes cause serious bacterial infections in humans that may be deadly. Not much is known about why and when this is the case. We tested the hypothesis that residual veterinary antibiotics in meat can disrupt the fermentation process, giving pathogenic bacteria a chance to survive and multiply. We found that six commercially available starter cultures were susceptible to commonly used antibiotics, namely, oxytetracycline, penicillin, and erythromycin. In meat, statutorily tolerable levels of oxytetracycline and erythromycin inhibited fermentation performance of three and five of the six starter cultures, respectively. In model sausages, the disruption of meat fermentation enhanced survival of the pathogens
Escherichia coli
O157:H7 and
Salmonella enterica
serovar Typhimurium compared to successful fermentations. Our work reveals an overlooked risk associated with the presence of veterinary drugs in meat.

IMPORTANCE
Antibiotics have for a long time been used as growth promoters in farm animals, and while they are banned as such in Europe, their clinical use in farm animals still accounts for the majority of consumption. Here, we examined how acceptable levels of antibiotics in meat influence fermentation. Our results show that commonly used bacterial starter cultures are sensitive to residual antibiotics at or near statutorily tolerable levels, and as a result, processed sausages may indeed contain high levels of pathogens. Our findings provide a possible explanation for outbreaks and disease cases associated with consumption of fermented sausages and offer yet another argument for limiting the use of antimicrobials in farm animals.
Comparative Genomics of Early-Diverging
Brucella
Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway
Authors: Wattam Alice R. , Inzana Thomas J. , Williams Kelly P. , Mane Shrinivasrao P. , Shukla Maulik , Almeida Nalvo F. , Dickerman Allan W. , Mason Steven , Moriyón Ignacio , O’Callaghan David , Whatmore Adrian M. , Sobral Bruno W. , Tiller Rebekah V. , Hoffmaster Alex R. , Frace Michael A. , De Castro Cristina , Molinaro Antonio , Boyle Stephen M. , De Barun K. , Setubal João C.
Published: August 2012

Brucella
species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (
Brucella inopinata
BO1
T
and
B. inopinata
-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted. Here we present a phylogenomic analysis of the draft genome sequences of BO1
T
and BO2 and of the Australian rodent strains 83-13 and NF2653 that shows that they form two groups well separated from the other sequenced
Brucella
spp. Several important differences were noted. Both BO1
T
and BO2 did not agglutinate significantly when live or inactivated cells were exposed to monospecific A and M antisera against O-side chain sugars composed of
N-
formyl-perosamine. While BO1
T
maintained the genes required to synthesize a typical
Brucella
O-antigen, BO2 lacked many of these genes but still produced a smooth LPS (lipopolysaccharide). Most missing genes were found in the
wbk
region involved in O-antigen synthesis in classic smooth
Brucella
spp. In their place, BO2 carries four genes that other bacteria use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and chemical analyses showed that BO2 carries an antigenically different O-antigen made of repeating hexose-rich oligosaccharide units that made the LPS water-soluble, which contrasts with the homopolymeric O-antigen of other smooth brucellae that have a phenol-soluble LPS. The results demonstrate the existence of a group of early-diverging brucellae with traits that depart significantly from those of the
Brucella
species described thus far.

IMPORTANCE
This report examines differences between genomes from four new
Brucella
strains and those from the classic
Brucella
spp. Our results show that the four new strains are outliers with respect to the previously known
Brucella
strains and yet are part of the genus, forming two new clades. The analysis revealed important information about the evolution and survival mechanisms of
Brucella
species, helping reshape our knowledge of this important zoonotic pathogen. One discovery of special importance is that one of the strains, BO2, produces an O-antigen distinct from any that has been seen in any other
Brucella
isolates to date.
The Role of Bacterial Enhancer Binding Proteins as Specialized Activators of σ54-Dependent Transcription
Authors: Bush Matthew , Dixon Ray
Published: August 2012

Bacterial enhancer binding proteins (bEBPs) are transcriptional activators that assemble as hexameric rings in their active forms and utilize ATP hydrolysis to remodel the conformation of RNA polymerase containing the alternative sigma factor σ54. We present a comprehensive and detailed summary of recent advances in our understanding of how these specialized molecular machines function. The review is structured by introducing each of the three domains in turn: the central catalytic domain, the N-terminal regulatory domain, and the C-terminal DNA binding domain. The role of the central catalytic domain is presented with particular reference to (i) oligomerization, (ii) ATP hydrolysis, and (iii) the key GAFTGA motif that contacts σ54for remodeling. Each of these functions forms a potential target of the signal-sensing N-terminal regulatory domain, which can act either positively or negatively to control the activation of σ54-dependent transcription. Finally, we focus on the DNA binding function of the C-terminal domain and the enhancer sites to which it binds. Particular attention is paid to the importance of σ54to the bacterial cell and its unique role in regulating transcription.