bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous surface charge polarizable continuum models of solvation. I. General formalism
Authors: Scalmani Giovanni , Frisch Michael J.
Published: March 2010

Continuum solvation models are appealing because of the simplified yet accurate description they provide of the solvent effect on a solute, described either by quantum mechanical or classical methods. The polarizable continuum model (PCM) family of solvation models is among the most widely used, although their application has been hampered by discontinuities and singularities arising from the discretization of the integral equations at the solute-solvent interface. In this contribution we introduce a continuous surface charge (CSC) approach that leads to a smooth and robust formalism for the PCM models. We start from the scheme proposed over ten years ago by York and Karplus and we generalize it in various ways, including the extension to analytic second derivatives with respect to atomic positions. We propose an optimal discrete representation of the integral operators required for the determination of the apparent surface charge. We achieve a clear separation between “model” and “cavity” which, together with simple generalizations of modern integral codes, is all that is required for an extensible and efficient implementation of the PCM models. Following this approach we are now able to introduce solvent effects on energies, structures, and vibrational frequencies (analytical first and second derivatives with respect to atomic coordinates), magnetic properties (derivatives with respect of magnetic field using GIAOs), and in the calculation more complex properties like frequency-dependent Raman activities, vibrational circular dichroism, and Raman optical activity.
Dissociation of NaCl in water from ab initio molecular dynamics simulations
Authors: Timko Jeff , Bucher Denis , Kuyucak Serdar
Published: March 2010

We perform ab initio molecular dynamics simulations to study the dissociation of NaCl in water. The potential of mean force (PMF) between the two ions is determined using the constrained-force method. The simulation windows corresponding to the contact and solvent-separated minima, and the transition state in between, are further analyzed to determine the changes in the properties of hydration waters such as coordination number, dipole moment, and orientation. The ab initio results are compared with those obtained from classical molecular dynamics simulations of aqueous NaCl using several common force fields. The ab initio PMF is found to have a shallower contact minimum and a smaller transition barrier compared with the classical ones. Also the binding free energy calculated from the ab initio PMF almost vanishes whereas it is negative for all the classical PMFs. Water dipole moments are observed to exhibit little change during dissociation, indicating that description of NaCl with a nonpolarizable force field may be feasible. However, overcoordination of the ion pair at all distances remains as a serious shortcoming of the current classical models. The ab initio results presented here provide useful guidance for alternative parametrizations of the nonpolarizable force fields as well as the polarizable ones currently under construction.
Photochromism and visible light induced H2 generation in Sr2TiO4:Cr complexes
Authors: Yi Z. G. , Iwai H. , Ye J. H.
Published: March 2010

Sr 2 TiO 4 : Cr complexes are found to possess photochromism. After the photochromism, the catalytic performance of the complexes for H2 generation increases markedly. In fact, it was found that the performance increased more than 20 times compared to the original Sr2TiO4: 10 mol % Cr complex. These results suggest that it is worthwhile searching and optimizing visible-light-sensitive photocatalysts by investigating possible photochromism.
Efficient local fixing of photorefractive polymer hologram using a laser beam
Authors: Li Guoqiang , Wang Peng
Published: March 2010

We propose and demonstrate a novel technique for efficient local fixing of photorefractive polymer hologram using a laser beam. In the technique, a CO2 laser beam is used to heat the sample and a local hologram can be fixed easier than previous methods. By using thinner glass substrates for the photorefractive device, the hologram can be fixed efficiently and at much faster speed. The fixation efficiency can be greater than 80% and the hologram can be fixed in the order of a second. This technique is critical for dynamic holographic three-dimensional display and holographic data storage.
Continuous-wave backward frequency doubling in periodically poled lithium niobate
Authors: Stivala S. , Busacca A. C. , Curcio L. , Oliveri R. L. , Riva-Sanseverino S. , Assanto Gaetano
Published: March 2010

We report on backward second-harmonic-generation in bulk periodically poled congruent lithium niobate with a 3.2 μm period. A tunable continuous-wave Ti:sapphire laser allowed us exciting two resonant quasi-phase-matching orders in the backward configuration. The resonances were also resolved by temperature tuning and interpolated with standard theory to extract relevant information on the sample.
Irreversibility of field-induced magnetostructural transition in NiCoMnSb shape memory alloy revealed by magnetization, transport and heat capacity studies
Authors: Nayak Ajaya K. , Suresh K. G. , Nigam A. K.
Published: March 2010

The effects of magnetic field on the martensitic transition have been studied in Ni45Co5Mn38Sb12. We find a large field-induced irreversibility in this system, as revealed by the field dependence of resistivity, magnetization, and heat capacity data. At the critical temperature, the field-induced conversion of the martensitic to austenite phase is not reversible under any field variation. At this temperature any energy fluctuation induces nucleation and growth of the equilibrium austenite phase at the expense of the metastable martensitic phase and gets arrested. All these three measurements completely rule out the coexistence of austenite and martensitic phases in the irreversibility regime.
Achieving a balanced life in the face of chronic illness
Authors: Jeon Yun-Hee , Jowsey Tanisha , Yen Laurann , Glasgow Nicholas J. , Essue Beverley , Kljakovic Marjan , Pearce-Brown Carmen , Mirzaei Masoud , Usherwood Tim , Jan Stephen , Kraus Stefan G. , Aspin Clive
Published: March 2010

The increasing prevalence of chronic disease is a driver of health system reform in most economically advanced nations. A consistent theme within these reforms is building greater patient-centredness into the health care delivery. This study aims to develop an in-depth understanding of the experience of patients and family carers affected by chronic illness that will be the basis on which to propose policy and health system interventions that are patient-centred. Participants struggled with the ongoing tasks of balancing their lives with the increasing demands and intrusion of chronic illness. Their attempts to achieve a balance were seriously hampered by fragmented services, complexity in navigating health services, relationships with health professionals and others, and co-morbidity. Future policy directions include designing models of care and infrastructure that enable patients and their family carers to balance life and illness, and aligning patient-centred care not only within health services but also with community and social support services.
What do general practitioners consider support? Findings from a local pilot initiative
Authors: Sankaranarayanan Anoop , Allanson Kerry , Arya Dinesh K.
Published: March 2010

This paper reports the findings of a local pilot that was aimed to assess if making a local psychiatrist available would improve GP satisfaction with regard to responsiveness and access to specialist mental health services. A psychiatrist was made available via a telephone advice line for 1 h every day. Pre- and post-survey of all GPs was conducted to elicit GP satisfaction and suggestions. The pilot was conducted from Maitland, the base of Hunter Valley Mental Health Service. A total of 202 GPs in the area were contacted and surveyed; 17% responded to the pre-survey and 27% to the post-survey. Only 8% of the GPs used the telephone advice service. Despite low use, most responding GPs indicated that they would like to see the services continue. Most of the responding GPs (both users and non-users of this service) were not aware of or had not used the Royal Australian College of General Practitioners’ GP Psych Support initiative. Results from this pilot indicate that making a local psychiatrist available improves GP satisfaction with regard to responsiveness and access, despite low use. Further research is needed to establish if such a service can be made available at an area level and whether this would be cost effective.
Partner or perish: experiences from the field about collaborations for reform
Authors: Boyer Kim , Orpin Peter , Walker Judith
Published: March 2010

Collaborations between researchers, policy makers, service providers and community members are critical to the journey of health service reform. Challenges are multifaceted and complex. Partners come with a variety of challenging agendas, value sets and imperatives, and see the drivers for reform from different perspectives. Different skills are required for managing the partnership and for providing academic leadership, and different structural frameworks need to be put in place for each task in each project. We have found through a series of partnerships across our research theme of healthy ageing, and consequent translation into policy and practice, that significant and innovative effort is required for both the collaboration and the research to succeed. A shared understanding of the issues and challenges is a start, but not sufficient for longer-term success. In addition to managing the research, our experience has demonstrated the need to understand the different challenges faced by each of the partners, recognise and respect personal and organisational value systems, and to establish separate mechanisms to manage strong egos alongside, but outside of, the research process.
What doctors want? A consultation method when the patient is a doctor
Authors: Kay Margaret , Mitchell Geoffrey , Clavarino Alexandra
Published: March 2010

Doctors face many barriers accessing health care. Even after a doctor has adopted the patient role, quality health care can remain elusive. This study investigated the consultation between the treating doctor and the doctor-patient. We aimed to determine what doctors want within the consultation, their preferred consultation method. This qualitative study involved 37 GPs who participated in one of six independently facilitated focus groups. Data were recorded, transcribed and analysed for recurrent themes using an iterative inductive framework. Participants emphasised the importance of, and the difficulty in, establishing a relationship with a GP. This involved determining who to see and when to go to the doctor. Specific ways of strengthening the doctor–patient relationship were discussed, including understanding the illness experience, acknowledging the whole patient, setting boundaries, providing holistic care, developing rapport and participating in shared decision making. Empathy was especially important. Analysis revealed strong similarities with the ‘patient-centred consultation method’. Understanding the preferred consultation method for doctors will assist doctors in providing quality care to their peers. This is an important step in enhancing health access for doctors. Doctors want what patients want: care delivered within a patient-centred consultation. These insights may help other health professionals when treating or receiving care from their colleagues.
A complexity perspective on health care improvement and reform in general practice and primary health care
Authors: Booth Barbara J. , Zwar Nicholas , Harris Mark
Published: March 2010

Health care improvement is always on the planning agenda but can prove frustrating when ‘the system’ seems to have a life of its own and responds in unpredictable ways to reform initiatives. Looking back over 20 years of general practice and primary health care in Australia, there has been plenty of planning and plenty of change, but not always a direct cause and effect relationship between the two. This article explores in detail an alternative view to the current orthodoxy of design, control and predictability in organisational change. The language of complexity is increasingly fashionable in talking about the dynamics of organisational behaviour and health care improvement, but its popular use often ignores challenging implications. However, when interpreted through human sociology and psychology, a complexity perspective offers a better match with everyday human experience of change. As such, it offers some suggestions for leaders, policy makers and managers in health care: that uncertainty and paradox are inherent in organisational change; that health care reform must pay attention to the constraints and politics of the everyday; and that change in health systems results from the complex processes of relating among those involved and that neither ‘the system’ nor a few individuals can be accountable for overall performance and outcomes.
Reading First in Pennsylvania: Achievement Findings after Five Years
Authors: Bean Rita , Draper Jason , Turner Greg , Zigmond Naomi
Published: March 2010

This article reports on the student achievement outcomes for third graders in Reading First (RF) schools in Pennsylvania over the five years of implementation for the group as a whole, for disaggregated groups of third graders, and for third graders who received reading instruction in RF schools for one, two, and three years. We also present a school-level growth measure for representing school improvement and for characterizing the success of RF in Pennsylvania. Results indicate that third-grade students in these RF schools are making substantially more progress in third-grade reading than are students in other schools in Pennsylvania, there is an increase of nearly 24% of students performing at proficient or advanced level over the five years, and the students in the below basic range on the achievement measure declined nearly 18%. Further, the disaggregated data show that the achievement gap, though not closed, was reduced for all groups of third graders. Finally, nearly 80% of the RF schools were successful in accomplishing the two goals of Reading First: an increase in the percentage of students at grade level, and a reduction in the percentage of students who were seriously below grade level.
Jung's cultural writing and Modern man in search of a soul (1933): spiral essays and performing symbols
Authors: Rowland Susan
Published: March 2010

C. G. Jung published in English, in 1933, Modern man in search of a soul. This book, I argue, is a response to related problems of psychologists writing cultural analysis, and to the difficulty of writing down the psyche itself. Given that Jung's most foundational belief is of the importance of the unconscious as source of creativity and of mystery, writing itself has to make room for ‘other’ voices and ‘other’ ways of arguing, in addition to rational abstract concepts, in order to fulfil Jung's vision. Symbol, myth, narrative and, crucially, spiral form embody and enact the psyche in culture.
Hydrothermal Synthesis of Rhombus-like SmCO3OH Microplates and Its Photoluminescence Property Doped with Eu3+
Authors: Yin Xiao-bin , Zhang You-jin , Fang Zhi-yong , Xu Zhen-yu
Published: March 2010

Rhombus-like SmCO3OH microplates with the edge lengths ranging from 5 μm to 10 μm and the thickness about 1.5 μm were synthesized through a simple hydrothermal method using urea as the precipitance. The structure and properties of the rhombus-like SmCO3OH microplates were characterized by X-ray diffraction, field-emission scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The optical property of the rhombus-like SmCO3OH microplates doped with Eu3+ was investigated by photoluminescence. A broad and strong emission band at 677 nm was obtained, which can be contributed to producing light conversion film.
Electronic Structure Research on Lattice Stability of V, Nb, and Ta by Density Functional Theory
Authors: Tao Hui-jin , Wan Fang-ming , Chen Wei-min
Published: March 2010

The difference of energy and electronic structure of V, Nb, and Ta in different crystalline structures were investigated by different methods in density functional theory (DFT). Lattice constants, total energies, and densities of states of these metals were calculated using the plane-wave pseudopotential method in DFT. Results were compared with those of projector augmented wave method, CALPHAD method, and experiments. Total energy and electronic structure analyses showed that valence electrons mostly transferred from s to p or d state, changing obviously with both the crystal structure and the elemental period number from V to Ta and leading to stronger cohesion, higher cohesive energy and more stable lattice of heavier metals.
Effect of Calcination Temperature on La-Modified Al2O3 Catalysts for Vapor Phase Hydrofluorination of Acetylene to Vinyl Fluoride
Authors: Bi Qing-yuan , Lu Ji-qing , Xing Li-qiong , Guo Ming , Luo Meng-fei
Published: March 2010

A La-modified Al2O3 catalyst was prepared with deposition-precipitation method. The effect of calcination temperature on the reactivity for vapor phase hydrofluorination of acetylene to vinyl fluoride. The catalysts calcined at different temperatures were characterized using NH3-TPD, pyridine-FTIR, X-ray diffraction, and Raman techniques. It was found that the calcination process could not only change the structure of these catalysts but also modify the amount of surface acidity on the catalysts. The catalyst calcined at 400 °C exhibited the highest conversion of acetylene (94.6%) and highest selectivity to vinyl fluoride (83.4%) and lower coke deposition selectivity (0.72%). The highest activity was related to the largest amount of surface acidity on the catalyst, and the coke deposition was also related to the total amount of surface acidic sites.
A Regulated Complex of the Scaffolding Proteins PDZK1 and EBP50 with Ezrin Contribute to Microvillar Organization
Authors: LaLonde David P. , Garbett Damien , Bretscher Anthony
Published: March 2010

PDZK1 and ezrin, radixin, moesin binding phosphoprotein 50 kDa (EBP50) are postsynaptic density 95/disc-large/zona occludens (PDZ)-domain–containing scaffolding proteins found in the apical microvilli of polarized epithelial cells. Binary interactions have been shown between the tail of PDZK1 and the PDZ domains of EBP50, as well as between EBP50 and the membrane–cytoskeletal linking protein ezrin. Here, we show that these molecules form a regulated ternary complex in vitro and in vivo. Complex formation is cooperative because ezrin positively influences the PDZK1/EBP50 interaction. Moreover, the interaction of PDZK1 with EBP50 is enhanced by the occupancy of EBP50's adjacent PDZ domain. The complex is further regulated by location, because PDZK1 shuttles from the nucleus in low confluence cells to microvilli in high confluence cells, and this regulates the formation of the PDZK1/EBP50/ezrin complex in vivo. Knockdown of EBP50 decreases the presence of microvilli, a phenotype that can be rescued by EBP50 re-expression or expression of a PDZK1 chimera that is directly targeted to ezrin. Thus, when appropriately located, PDZK1 can provide a function necessary for microvilli formation normally provided by EBP50. By entering into the ternary complex, PDZK1 can both enhance the scaffolding at the apical membrane as well as augment EBP50's role in microvilli formation.
Malpractice Claims Associated with Medication Management for Chronic Pain
Authors: Fitzgibbon Dermot R. , Rathmell James P. , Michna Edward , Stephens Linda S. , Posner Karen L. , Domino Karen B.
Published: March 2010

Background

Medication management is an integral part of chronic pain management. Prompted by an increase in the role of medication management in anesthesia chronic pain liability, we investigated the characteristics of malpractice claims collected from 2005 to 2008.

Methods

After Institutional Review Board approval, we compared medication management claims with other chronic pain claims from the American Society of Anesthesiologists Closed Claims Database of 8,954 claims. Claims for death underwent in-depth analysis.

Results

Medication management represented 17% of 295 chronic non-cancer pain claims. Compared with other chronic pain claims, medication management patients tended to be younger men (P < 0.01) with back pain. Most patients were prescribed opioids (94%) and also additional psychoactive medications (58%). Eighty percent of patients had at least one factor commonly associated with medication misuse and 24% had >or= 3 factors. Most claims (82%) involved patients who did not cooperate in their care (69%) or inappropriate medication management by physicians (59%). Death was the most common outcome in medication management claims (57% vs. 9% in other chronic pain claims, P < 0.01). Factors associated with death included long-acting opioids, additional psychoactive medications, and >or= 3 factors commonly associated with medication misuse. Alleged addiction from prescribed opioids was the complaint in 24%. Appropriateness of care and payments was similar for medication management versus other chronic pain claims.

Conclusions

Most anesthesia malpractice claims for medication management problems involved patients with a history of risk behaviors commonly associated with medication misuse. Malpractice claims arising from medication management had a high proportion of deaths with both patient and physician contributions to the outcome.
Limb Remote Ischemic Preconditioning Protects the Spinal Cord from Ischemia–Reperfusion Injury
Authors: Dong Hai-Long , Zhang Yi , Su Bin-Xiao , Zhu Zheng-Hua , Gu Qiu-Han , Sang Han-Fei , Xiong Lize
Published: March 2010

Background

It remains to be established whether spinal cord ischemic tolerance can be induced by limb remote ischemic preconditioning (RIPC), and the mechanisms underlying the neuroprotective effects of RIPC on the spinal cord need to be clarified.

Methods

Spinal cord ischemia was studied in New Zealand White rabbits. In experiment 1, all rabbits were subjected to 20-min spinal cord ischemia by aortic occlusion. Thirty minutes before ischemia, rabbits were subjected to sham intervention or RIPC achieved by bilateral femoral artery occlusion (10 min ischemia/10 min reperfusion, two cycles). Dimethylthiourea (500 mg/kg, intravenously), a hydroxyl radical scavenger, or vehicle was given 1 h before RIPC. Antioxidant enzyme activity was measured along with spinal cord histology and neurologic function. In experiment 2, rabbits were subjected to spinal cord ischemia, with or without RIPC. In addition, rabbits were pretreated with various doses of hexamethonium.

Results

RIPC improved neurologic function and reduced histologic damage. This was associated with increased endogenous antioxidant activity. Dimethylthiourea inhibited the protective effects of RIPC. In contrast, there was no effect of hexamethonium on the protective effect of RIPC.

Conclusions

An initial oxidative stress acts as a trigger to upregulate antioxidant enzyme activity, rather than the neural pathway, and plays an important role in the formation of the tolerance against spinal cord ischemia by limb RIPC.
Plasma Proteome to Look for Diagnostic Biomarkers of Early Bacterial Sepsis after Liver Transplantation
Authors: Paugam-Burtz Catherine , Albuquerque Miguel , Baron Gabriel , Bert Frederic , Voitot Hélène , Delefosse Didier , Dondero Federica , Sommacale Daniele , Francoz Claire , Hanna Nadine , Belghiti Jacques , Ravaud Philippe , Bedossa Pierre , Mantz Jean , Paradis Valérie
Published: March 2010

Background

While outcome continuously improves after liver transplantation, sepsis remains the leading cause of early postoperative mortality. Diagnosis of infections remains particularly difficult in these patients. This study used plasma profiling coupling Proteinchip array with surface-enhanced laser desorption ionization time-of-fly mass spectrometry to search for biomarkers of postoperative sepsis in patients who underwent liver transplantation.

Methods

Diagnosis of sepsis at day 5 relied on widely accepted clinical signs and positive culture of microbiologic samples. Profiles of day 5 plasma were obtained from SELDI-TOF CM10 chip (BioRad, Marnes-la-Coquette, France) analysis. Mean peak intensity of proteins was compared between septic and nonseptic plasma by U test followed by analysis of the area under the receiver-operating characteristic for the significant peaks. Diagnostic performance of significant proteins was established in a derivation set and in a validation set.

Results

In the derivation set of 31 patients with and 30 without infection, 23 plasma protein peaks were differentially expressed between patients with and without sepsis. Combination of five peaks allowed sepsis diagnosis with a positive likelihood ratio of 12.5 and a C-statistics of 0.72, 95% CI 0.57-0.85. In the validation set of 31 patients with infection and 34 without infection, the five peaks were differentially expressed as well and allowed day 5 sepsis diagnosis with a positive likelihood ratio of 5.1 and C-statistics of 0.74 (0.58-0.85).

Conclusion

A combination of five plasma protein peaks may provide material for useful diagnostic biomarkers of postoperative sepsis in patients undergoing liver transplantation. However, these proteins remain to be identified.
Pharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in Dogs
Authors: Heerdt Paul M. , Malhotra Jaideep K. , Pan Brian Y. , Sunaga Hiroshi , Savarese John J.
Published: March 2010

Background

CW002 is a novel neuromuscular blocking drug with a duration dependent on the rate of cysteine adduction to the molecule. The current study characterized the pharmacodynamics and cardiopulmonary side effects of CW002 in dogs.

Methods

In eight beagles, the dose required to produce 95% neuromuscular blockade (ED95) for CW002 was first determined and cysteine reversibility was confirmed. Five to 7 days later, incrementally larger doses were injected starting with 6.25 x ED95 and doubling the dose every 15 min. Before and after injection, blood was obtained for histamine analysis. Systemic and pulmonary arterial pressures, cardiac output, and left ventricular pressure and volume were recorded along with inspiratory pressure and pulmonary compliance. Ventricular contractility and lusitropy were indexed from pressure and volume data.

Results

The ED95 for CW002 from pooled data was 0.009 mg/kg. At 3 x ED95, onset time was 2.6 +/- 0.9 min and duration was 47 +/- 9 min. The duration was shortened to 3.7 +/- 0.6 min by 50 mg/kg L-cysteine injected 1 min after CW002. At 25 x ED95, CW002 reduced mean arterial pressure with concomitant decreases in systemic vascular resistance, mean pulmonary artery pressure, cardiac output, contractility, and lusitropy, beginning at 50 x ED95. However, even at a dose of 100 x ED95, the average change in any variable was less than 20%. There were no changes in pulmonary vascular resistance or ventilation mechanics at any dose, and histamine release occurred in only two of eight animals.

Conclusions

CW002 is a potent neuromuscular blocking drug that at doses up to 100 x ED95 produces modest hemodynamic effects that are not associated with bronchoconstriction or consistent histamine release.
Anesthesiology Residents' Performance of Pediatric Resuscitation during a Simulated Hyperkalemic Cardiac Arrest
Authors: Howard-Quijano Kimberly J. , Stiegler Marjorie A. , Huang Yue Ming , Canales Cecilia , Steadman Randolph H.
Published: March 2010

Background

Anesthesiologists are responsible for the management of perioperative cardiopulmonary arrest in children. This study used simulation to assess the pediatric resuscitation skills of experienced anesthesia residents.

Methods

Nineteen anesthesia residents were evaluated using a pediatric pulseless electrical activity scenario. The authors used a standardized checklist to evaluate the residents' diagnostic and therapeutic interventions.

Results

After the onset of pulseless electrical activity, 79% of residents initiated cardiopulmonary resuscitation within 1 min. Approximately one third (31%) performed chest compressions at the recommended rate. Epinephrine was administered by 95% of residents, but only one third used the correct pediatric dose. All residents administered fluid boluses, but only 16% administered the recommended volume. Only one fourth of the residents considered hyperkalemia as a cause of pulseless electrical activity. None of the residents asked for dosing aids.

Conclusion

During this simulated pediatric emergency, anesthesia residents demonstrated an acceptable knowledge of general resuscitation maneuvers. However, a subset of resuscitation skills was incorrectly performed, mostly related to age or weight. Importantly, many residents did not consider the full differential diagnosis of pulseless electrical activity. Anesthesia residents may benefit from additional pediatric resuscitation training and practice using cognitive aids to access dosages and complicated diagnostic algorithms.
Gantacurium and CW002 Do Not Potentiate Muscarinic Receptor-mediated Airway Smooth Muscle Constriction in Guinea Pigs
Authors: Sunaga Hiroshi , Zhang Yi , Savarese John J. , Emala Charles W.
Published: March 2010

Background

Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors, undesirable airway effects (i.e., bronchoconstriction) can result from neuromuscular blocking agents' affinity for airway muscarinic receptors. We questioned whether two new members of a bisquaternary nondepolarizing muscle relaxant family, gantacurium and CW002, demonstrated detrimental effects of airway muscarinic receptors using an in vivo model in guinea pig airways.

Methods

Urethane-anesthetized male guinea pigs were ventilated through a tracheostomy with continuous digital recordings of pulmonary inflation pressure and heart rate. The dose for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium was defined in the guinea pig. Transient and reproducible changes in pulmonary inflation pressure and heart rate were recorded after vagal nerve stimulation or intravenous injection of acetylcholine before and after pretreatment with cumulatively increasing concentrations of gantacurium, CW002, cisatracurium or a single concentration of rapacuronium.

Results

The doses for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium were 0.064 +/- 0.006, 0.012 +/- 0.0006, 0.10 +/- 0.003, and 0.31 +/- 0.05 mg/kg, respectively. Gantacurium, CW002, and cisatracurium were without effects on baseline pulmonary inflation pressures and were devoid of significant interactions with M2 and M3 muscarinic receptors in vivo.

Conclusion

These findings suggest that gantacurium and CW002 are devoid of significant effects at airway muscarinic receptors particularly M3 receptors on bronchial smooth musculature at doses several fold higher than those required for functional muscle paralysis.
Role of Intraoperative and Postoperative Blood Glucose Concentrations in Predicting Outcomes after Cardiac Surgery
Authors: Duncan Andra E. , Abd-Elsayed Alaa , Maheshwari Ankit , Xu Meng , Soltesz Edward , Koch Colleen G.
Published: March 2010

Background

Severe hyperglycemia is associated with adverse outcomes after cardiac surgery. Whether intraoperative and postoperative glucose concentrations equally impact outcomes is unknown. The objective of this investigation was to compare the ability of perioperative glucose concentrations and glycemic variability to predict adverse outcomes. Risk associated with decreasing increments of glucose concentrations, hypoglycemia, and diabetic status was also examined.

Methods

This retrospective analysis of prospectively collected data included 4,302 patients who underwent cardiac surgery between October 3, 2005 and May 31, 2007 at the Cleveland Clinic. Time-weighted mean intraoperative (GlcOR) and postoperative (GlcICU) glucose concentrations were calculated. Patients were categorized as follows: Glc more than 200, 171-200, 141-170, and less than or equal to 140 mg/dl. Coefficient of variation was used to calculate glycemic variability. Logistic regression model with backward selection assessed the relationship between glucose concentrations, variability, and adverse outcomes while adjusting for potential confounders. Another model assessed the predictability of GlcOR and GlcICU on adverse outcomes.

Results

Both GlcOR and GlcICU predicted risk for mortality and morbidity. Increased postoperative glycemic variability was associated with increased risk for adverse outcomes. Severe hyperglycemia (GlcOR and GlcICU > 200 mg/dl) was associated with worse outcomes; however, decreasing increments of GlcOR did not consistently reduce risk. GlcOR less than or equal to 140 mg/dl was not associated with improved outcomes compared with severe hyperglycemia, despite infrequent hypoglycemia. Diabetic status did not influence the effects of hyperglycemia.

Conclusion

Perioperative glucose concentrations and glycemic variability are important in predicting outcomes after cardiac surgery. Incremental decreases of intraoperative glucose concentrations did not consistently reduce risk. Despite rare hypoglycemia, intraoperative glucose concentrations closest to normoglycemia were associated with worse outcomes.
Simulation-based Training Improves Physicians' Performance in Patient Care in High-stakes Clinical Setting of Cardiac Surgery
Authors: Bruppacher Heinz R. , Alam Syed K. , LeBlanc Vicki R. , Latter David , Naik Viren N. , Savoldelli Georges L. , Mazer C. David , Kurrek Matt M. , Joo Hwan S.
Published: March 2010

Background

Simulation-based training is useful in improving physicians' skills. However, no randomized controlled trials have been able to demonstrate the effects of simulation teaching in real-life patient care. This study aimed to determine whether simulation-based training or an interactive seminar resulted in better patient care during weaning from cardiopulmonary bypass (CPB)-a high stakes clinical setting.

Methods

This study was conducted as a prospective, single-blinded, randomized controlled trial. After institutional research board approval, 20 anesthesiology trainees, postgraduate year 4 or higher, inexperienced in CPB weaning, and 60 patients scheduled for elective coronary artery bypass grafting were recruited. Each trainee received a teaching syllabus for CPB weaning 1 week before attempting to wean a patient from CPB (pretest). One week later, each trainee received a 2-h training session with either high-fidelity simulation-based training or a 2-h interactive seminar. Each trainee then weaned patients from CPB within 2 weeks (posttest) and 5 weeks (retention test) from the intervention. Clinical performance was measured using the validated Anesthesiologists' Nontechnical Skills Global Rating Scale and a checklist of expected clinical actions.

Results

Pretest Global Rating Scale and checklist performances were similar. The simulation group scored significantly higher than the seminar group at both posttest (Global Rating Scale [mean +/- standard error]: 14.3 +/- 0.41 vs. 11.8 +/- 0.41, P < 0.001; checklist: 89.9 +/- 3.0% vs. 75.4 +/- 3.0%, P = 0.003) and retention test (Global Rating Scale: 14.1 +/- 0.41 vs. 11.7 +/- 0.41, P < 0.001; checklist: 93.2 +/- 2.4% vs. 77.0 +/- 2.4%, P < 0.001).

Conclusion

Skills required to wean a patient from CPB can be acquired through simulation-based training. Compared with traditional interactive seminars, simulation-based training leads to improved performance in patient care by senior trainees in anesthesiology.
Statistical Evaluation of a Biomarker
Authors: Ray Patrick , Manach Yannick Le , Riou Bruno , Houle Tim T. , Warner David S.
Published: March 2010

A biomarker may provide a diagnosis, assess disease severity or risk, or guide other clinical interventions such as the use of drugs. Although considerable progress has been made in standardizing the methodology and reporting of randomized trials, less has been accomplished concerning the assessment of biomarkers. Biomarker studies are often presented with poor biostatistics and methodologic flaws that precludes them from providing a reliable and reproducible scientific message. A host of issues are discussed that can improve the statistical evaluation and reporting of biomarker studies. Investigators should be aware of these issues when designing their studies, editors and reviewers when analyzing a manuscript, and readers when interpreting results.
Ontogenetic development of migration: Lagrangian drift trajectories suggest a new paradigm for sea turtles
Authors: Hays Graeme C. , Fossette Sabrina , Katselidis Kostas A. , Mariani Patrizio , Schofield Gail
Published: March 2010

Long distance migration occurs in a wide variety of taxa including birds, insects, fishes, mammals and reptiles. Here, we provide evidence for a new paradigm for the determinants of migration destination. As adults, sea turtles show fidelity to their natal nesting areas and then at the end of the breeding season may migrate to distant foraging sites. For a major rookery in the Mediterranean, we simulated hatchling drift by releasing 288 000 numerical particles in an area close to the nesting beaches. We show that the pattern of adult dispersion from the breeding area reflects the extent of passive dispersion that would be experienced by hatchlings. Hence, the prevailing oceanography around nesting areas may be crucial to the selection of foraging sites used by adult sea turtles. This environmental forcing may allow the rapid evolution of new migration destinations if ocean currents alter with climate change.
Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients
Authors: Grion Cintia M. C. , Cardoso Lucienne T. Q. , Perazolo Tatianna F. , Garcia Alexandre S. , Barbosa Décio S. , Morimoto Helena Kaminami , Matsuo Tiemi , Carrilho Alexandre J. F.
Published: March 2010

Eur J Clin Invest 2010; 40 (4): 330–338

Background  The magnitude of lipoprotein level reduction during the acute‐phase response may be associated with the severity and mortality of sepsis. However, it remains to be determined whether low lipoprotein levels can be considered a risk factor for developing sepsis. We aimed to investigate lipoprotein levels as risk factors for sepsis in hospitalized patients, and also describe sequential changes in lipoprotein and cholesterol ester transfer protein (CETP) levels during sepsis.

Design  This is a prospective cohort study and case–control analysis from selected hospitalized patients. Blood samples were collected at admission, and participants were monitored for severe sepsis. Total cholesterol, high density lipoprotein (HDL), low density lipoprotein, and triglyceride levels were compared between sepsis cases and controls. Cholesterol, apolipoprotein, phospholipid and CETP concentrations were monitored in the case group.

Results  Of 1719 enrolled patients, 51 developed severe sepsis and were paired with 71 controls by age, gender, presence of infection at admission and chronic disease. HDL cholesterol level at admission was a risk factor for severe sepsis (OR = 0·969; 95% CI: 0·944–0·995). Mean CETP levels diminished between hospital admission and day 3 of sepsis. The magnitude of this variation (ΔCETP) was more pronounced in non‐survivors (0·78 ± 1·08 μg mL−1) than that in survivors (0·02 ± 0·58 μg mL−1, P = 0·01).

Conclusions  HDL cholesterol may have a protective effect against sepsis. Each 1 mg dL−1 increase in HDL decreased the odds of severe sepsis by 3% during hospitalization. The reduction of plasma CETP was associated with mortality.
Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease
Authors: Lorenzen Johan , Krämer Robert , Kliem Volker , Bode‐Boeger Stefanie M. , Veldink Hendrik , Haller Hermann , Fliser Danilo , Kielstein Jan T.
Published: March 2010

Eur J Clin Invest 2010; 40 (4): 294–300

Background  The pleiotropic cytokine osteopontin (OPN) is thought to be involved in the pathogenesis of atherosclerosis. However, the relationship between OPN and renal function, a cardiovascular risk factor itself, is not known. Therefore, we assessed the relationship between OPN plasma levels and renal function in patients at different stages of chronic kidney disease (CKD).

Methods  We studied 49 non‐diabetic and non‐smoking patients with primary kidney disease at different CKD stages (K/DOQI 1‐5). True glomerular filtration rate (GFR) in patients was assessed using the inulin‐clearance technique. To examine the role of an abrupt change in GFR on circulating OPN, 15 living related kidney donors were studied before and after unilateral nephrectomy. Twenty matched non‐smoking healthy subjects served as controls.

Results  OPN plasma levels in patients with CKD stage 1 (i.e. GFR above 90 mL min−1 1·73 m−2) were comparable with controls. OPN levels increase in a linear fashion with declining GFR (r = −0·9, P < 0·0001), so that the increase in OPN mirrors the severity of renal impairment. After unilateral nephrectomy, circulating OPN increased significantly in parallel to the decrease in GFR. We found a direct association between OPN and other markers of renal function (serum‐creatinine, homocysteine and symmetric dimethylarginine,) as well as with cardiovascular risk factors such as asymmetric dimethylarginine (r = 0·36, P = 0·0213).

Conclusion  There is a close inverse association between GFR and circulating OPN in patients with CKD. Furthermore, OPN plasma levels correlate with established cardiovascular risk markers in patients with CKD. Assessment of renal function is important for the interpretation of OPN levels in patients with atherosclerotic disease.
The Haiti Earthquake: a salutary lesson in (non) earthquake engineering
Authors: Styles Peter
Published: March 2010

A devastating earthquake of magnitude 7 struck very close and almost beneath Port au Prince the capital of Haiti, the western half of the island of Hispaniola, early in the morning of Tuesday, 12 January 2010 (Fig. 1). While in absolute terms this was by no means the largest earthquake recorded this year globally, the death toll is around 230 000, making it one of the world's worst earthquakes in terms of casualties in recorded history, with almost uncountable economic loss to one of the poorest countries in the world.

Intensity map of 2010 Haiti earthquake (Image: USGS).

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Assessing the immunopotency of Toll‐like receptor agonists in an in vitro tissue‐engineered immunological model
Authors: Ma Yifan , Poisson Louis , Sanchez‐Schmitz Guzman , Pawar Santosh , Qu Chunfeng , Randolph Gwendalyn J. , Warren William L. , Mishkin Eric M. , Higbee Russell G.
Published: March 2010

The in vitro Peripheral Tissue Equivalent (PTE) module is a three‐dimensional tissue‐engineered endothelial cell/collagen matrix culture system, which has been reported to reproduce in vivo physiological conditions and which generates dendritic cells (DC) autonomously. In the present study, we used the PTE module to investigate the immunopotency of Toll‐like receptor (TLR) agonists, including polyinosine‐polycytidylic acid, Gardiquimod, CpG 2006 and lipopolysaccharide. Application of TLR agonists in the PTE module induced a wide range of cytokines, including interleukins 1α/β, 6, 8 and 10 and tumour necrosis factor‐α. Compared with traditional peripheral blood mononuclear cell (PBMC) cultures, the PTE module produced twofold to 100‐fold higher levels of cytokine secretion, indicating that it can be a highly sensitive assay system. This increased sensitivity is the result of the natural synergy between the leucocytes and the endothelium. Furthermore, the application of TLR agonists, such as lipopolysaccharide and Gardiquimod, to the PTE module enhanced DC differentiation and promoted DC maturation, as indicated by up‐regulated expression of CD83, CD86 and CCR7(CD197). In addition, functional assays indicated PTE‐derived DC treated with Gardiquimod, a TLR‐7 agonist, significantly augmented anti‐tetanus toxoid antibody production. Interestingly, replacing PBMC with purified myeloid cells (CD33+) significantly reduced the responsiveness of the PTE module to TLR stimulation. The reduced sensitivity was partly the result of the removal of plasmacytoid DC that participated in the response to TLR stimulation and sensitization of the PTE module. Overall, the in vitro PTE module clearly demonstrated the effects of TLR agonists on DC generation, maturation and antigen‐presenting capacity, and may serve as a sensitive and predictive test bed for the evaluation of adjuvant candidates.
Quantifying the effect of interactions between disease control, nitrogen supply and land use change on the greenhouse gas emissions associated with wheat production
Authors: Berry P. M. , Kindred D. R. , Olesen J. E. , Jorgensen L. N. , Paveley N. D.
Published: March 2010

A method for calculating the effect of disease control on greenhouse gas (GHG) emissions associated with wheat production, reported previously, was developed further to account for effects of disease control on the amount of fertilizer nitrogen (N) which should be applied and on changes in land use. Data from nine randomized and replicated field experiments from the UK and Denmark showed that the economic optimum N input to winter wheat was greater if diseases were controlled by fungicides, than for untreated wheat. The GHGs associated with this additional N largely negated the benefit to emissions per tonne of grain resulting from disease control. However, the mean grain yield obtained without fungicide treatment was 6·71 t ha−1, compared to 8·88 t ha−1 with fungicide treatment, if N input was optimal for each situation. In the absence of disease control by fungicides, and assuming that the optimum N rate was used, an additional 481 kha of wheat would be required to maintain UK wheat production at the current level. If the additional land area came from converting temperate grassland to arable production, the GHG emissions caused by ploughing grassland would cause emissions to rise from 503 to 713 kg CO2e per tonne of grain produced. This would result in an additional 3·15 Mt CO2e per year to produce the typical UK annual production of 15 Mt. This analysis reinforces the importance of winning the ‘arms race’ against pathogen evolution towards fungicide insensitivity and virulence.