bluuebunny/crossref_metadata_2025 huggingface dataset:
Meningococcal purpura fulminans in children: I. Initial orthopedic management
Authors: Nectoux E. , Mezel A. , Raux S. , Fron D. , Maillet M. , Herbaux B.
Published: August 2010

Background

Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis frequently causing early orthopedic lesions. Few studies have reported on the initial surgical management of acute purpura fulminans. The aim of this study is to look at the predictive factors in orthopedic outcome in light of the initial surgical management in children surviving initial resuscitation.

Methods

Nineteen patients referred to our institution between 1987 and 2005 were taken care of at the very beginning of the purpura fulminans. All cases were retrospectively reviewed so as to collect information on the total skin necrosis, vascular insufficiency, gangrene, and total duration of vasopressive treatment.

Results

All patients had multiorgan failure; only one never developed any skin necrosis or ischemia. Eighteen patients lost tissue, leading to 22 skin grafts, including two total skin grafts. There was only one graft failure. Thirteen patients were concerned by an amputation, representing, in total, 54 fingers, 36 toes, two transmetatarsal, and ten transtibial below-knee amputations, with a mean delay of 4 weeks after onset of the disease. Necrosis seems to affect mainly the lower limbs, but there is no predictive factor that impacted on the orthopedic outcome. We did not perform any fasciotomy or compartment pressure measurement to avoid non-perfusion worsening; nonetheless, our outcome in this series is comparable to existing series in the literature. V.A.C.® therapy could be promising regarding the management of skin necrosis in this particular context. While suffering from general multiorgan failure, great care should be observed not to miss any additional osseous or articular infection, as some patients also develop local osteitis and osteomyelitis that are often not diagnosed.

Conclusions

We do not advocate very early surgery during the acute phase of purpura fulminans, as it does not change the orthopedic outcome in these children. By performing amputations and skin coverage some time after the acute phase, we obtained similar results to those found in the literature.
ENDPOINT ESTIMATES FOR COMMUTATORS OF RIESZ TRANSFORMS ASSOCIATED WITH SCHRÖDINGER OPERATORS
Authors: LI PENGTAO , PENG LIZHONG
Published: August 2010

In this paper, we discuss the H1L-boundedness of commutators of Riesz transforms associated with the Schrödinger operator L=−△+V, where H1L(Rn) is the Hardy space associated with L. We assume that V (x) is a nonzero, nonnegative potential which belongs to Bq for some q>n/2. Let T1=V (x)(−△+V )−1, T2=V1/2(−△+V )−1/2 and T3 =∇(−△+V )−1/2. We prove that, for b∈BMO (Rn) , the commutator [b,T3 ] is not bounded from H1L(Rn) to L1 (Rn) as T3 itself. As an alternative, we obtain that [b,Ti ] , ( i=1,2,3 ) are of (H1L,L1weak) -boundedness.
UK Food Standards Agency Workshop Consensus Report: the choice of method for measuring 25-hydroxyvitamin D to estimate vitamin D status for the UK National Diet and Nutrition Survey
Authors: Hunty Anne de la , Wallace A. Michael , Gibson Sigrid , Viljakainen Heli , Lamberg-Allardt Christel , Ashwell Margaret
Published: August 2010

The consensus workshop, organised on behalf of the Food Standards Agency, was convened to recommend the most appropriate and secure method for measuring vitamin D status in the UK. Workshop participants (the Expert Panel) were invited on the basis of expertise in current 25-hydroxyvitamin D (25OHD) assays, or expertise in vitamin D nutrition and metabolism or detailed knowledge and experience in the National Diet and Nutrition Survey (NDNS). A decision support matrix, which set out the particular criteria by which the different options were scored and evaluated, was used to structure the discussion. The Expert Panel agreed that five methods for measuring 25OHD should be evaluated according to eleven criteria, selected on the basis of their relevance to the NDNS. All three of the evaluating subgroups of the Expert Panel produced similar total scores over the eleven criteria for the different methods; they scored LC–MS/MS and HPLC-UV similarly highly, while the scores for the immunoassay methods were lower. The Expert Panel recommended that an LC–MS/MS method should be the preferred method for the NDNS. A detailed specification for the method will be required to ensure comparability between NDNS and the National Health and Nutrition Examination Survey in the US facilitating future comparisons. The Expert Panel also recommended that the method should be carried out in a laboratory with appropriate expertise, competency and history of records of good performance. The method should be standardised against the National Institute of Standards and Technology SRM 972. If the recommended LC–MS/MS is adopted, the Expert Panel indicated that the method should be able to discriminate the C-3 epimer of 25OHD3, especially if used to measure 25OHD in young infants in the forthcoming Diet and Nutrition Survey of Infants and Young Children, who are known to have high circulating concentrations of the C-3 epimer.
Minimalist models for proteins: a comparative analysis
Authors: Tozzini Valentina
Published: August 2010

The last decade has witnessed a renewed interest in the coarse-grained (CG) models for biopolymers, also stimulated by the needs of modern molecular biology, dealing with nano- to micro-sized bio-molecular systems and larger than microsecond timescale. This combination of size and timescale is, in fact, hard to access by atomic-based simulations. Coarse graining the system is a route to be followed to overcome these limits, but the ways of practically implementing it are many and different, making the landscape of CG models very vast and complex.

In this paper, the CG models are reviewed and their features, applications and performances compared. This analysis, restricted to proteins, focuses on the minimalist models, namely those reducing at minimum the number of degrees of freedom without losing the possibility of explicitly describing the secondary structures. This class includes models using a single or a few interacting centers (beads) for each amino acid.

From this analysis several issues emerge. The difficulty in building these models resides in the need for combining transferability/predictive power with the capability of accurately reproducing the structures. It is shown that these aspects could be optimized by accurately choosing the force field (FF) terms and functional forms, and combining different parameterization procedures. In addition, in spite of the variety of the minimalist models, regularities can be found in the parameters values and in FF terms. These are outlined and schematically presented with the aid of a generic phase diagram of the polypeptide in the parameter space and, hopefully, could serve as guidelines for the development of minimalist models incorporating the maximum possible level of predictive power and structural accuracy.
The value of nature in Indian (Hindu) traditions
Authors: FRAMARIN CHRISTOPHER G.
Published: August 2010

Many authors claim that certain Indian (Hindu) texts and traditions deny that nature has intrinsic value. If nature has value at all, it has value only as a means tomokṣa(liberation). This view is implausible as an interpretation of any Indian tradition that accepts the doctrines ofahiṃsā(non-harm) andkarma. The proponent must explain the connection betweenahiṃsāand merit by citing the connection betweenahiṃsāandmokṣa:ahiṃsāis valuable, and therefore produces merit, becauseahiṃsāis instrumentally valuable as a means tomokṣa. Ahiṃsāis a means tomokṣa, however, because it produces merit. Hence the explanation is circular. Additionally, this view entails that morality is strictly arbitrary – it might just as well be thathiṃsā(harm) produces merit, andahiṃsāproduces demerit. An alternative interpretation that avoids these problems states that the value ofahiṃsāderives from the intrinsic value of the unharmed entities.
Counter-cultural religious experiences
Authors: DUMSDAY TRAVIS
Published: August 2010

Discussions of the evidential import of religious experiences have tended to focus on the intra-cultural variety: that is, experiences the content of which accord with the religious/cultural background of the experiencer (eg. someone raised in a Buddhist culture might experience the oneness of all, whereas someone from a Christian background might have a vision of Jesus). But what of counter-cultural experiences? That is, experiences which fall outside of the individual's religious/cultural background? Little attention has been paid to these, though such experiences are far from unheard of in the case study literature. In this paper I explore some preliminary questions surrounding the evidential import of counter-cultural religious experiences.
The global context for public health nutrition taxation
Authors: Thow Anne Marie , Heywood Peter , Leeder Stephen , Burns Lee
Published: August 2010

Objective

To assess critically the scope for public health nutrition taxation within the framework of the global tax reform agenda.

Design

Review of the tax policy literature for global policy priorities relevant to public health nutrition taxation; critical analysis of proposals for public health nutrition taxation judged against the global agenda for tax reform.

Setting

The global tax reform agenda shapes decisions of tax policy makers in all countries. By understanding this agenda, public health nutritionists can make feasible taxation proposals and thus improve the development, uptake and implementation of recommendations for nutrition-related taxation.

Results

The priorities of the global tax reform agenda relevant to public health nutrition taxation are streamlining of taxes, adoption of value-added tax (VAT), minimisation of excise taxes (except to correct for externalities) and removal of import taxes in line with trade liberalisation policies. Proposals consistent with the global tax reform agenda have included excise taxes, extension of VAT to currently exempted (unhealthy) foods and tariff reductions for healthy foods.

Conclusions

Proposals for public health nutrition taxation should (i) use existing types and rates of taxes where possible, (ii) use excise taxes that specifically address externalities, (iii) avoid differential VAT on foods and (iv) use import taxes in ways that comply with trade liberalisation priorities.
DEGREE SUPERVALUATIONAL LOGIC
Authors: WILLIAMS J. ROBERT G.
Published: August 2010

Supervaluationism is often described as the most popular semantic treatment of indeterminacy. There’s little consensus, however, about how to fill out the bare-bones idea to include a characterization of logical consequence. The paper explores one methodology for choosing between the logics: pick a logic thatnorms beliefas classical consequence is standardly thought to do. The main focus of the paper considers a variant of standard supervaluational, on which we can characterizedegrees of determinacy. It applies the methodology above to focus ondegree logic. This is developed first in a basic, single-premise case; and then extended to the multipremise case, and to allowdegreesof consequence. The metatheoretic properties of degree logic are set out. On the positive side, the logic is supraclassical—all classical valid sequents are degree logic valid. Strikingly, metarules such as cut and conjunction introduction fail.
Prokaryotic diversity pattern in high‐altitude ecosystems of the Chilean Altiplano
Authors: Demergasso Cecilia , Dorador Cristina , Meneses Daniela , Blamey Jenny , Cabrol Nathalie , Escudero Lorena , Chong Guillermo
Published: August 2010

The Chilean Altiplano is the westernmost part of a large volcanic‐sedimentary plateau in the central Andes. High solar irradiance and rapid increase of temperature have contributed to make it a hot spot of global climatic change. In this study, we describe microbial diversity in the summit lake of the Simba volcano (5,870 m) and the evaporitic basins of Salar de Aguas Calientes (4,200 m) and Laguna Lejía (4,325 m) using both culture and culture‐independent methods. The results obtained were analyzed together with available information from related environments to describe the traits of the microbial community driven by main environmental factors. Isolated cultures exhibit high resistance to all three types of UV radiation, further supporting the adaptation of microorganisms to the high altitude environment. The microbial community structures at Salar de Aguas Calientes and Laguna Lejía are similar to those from other saline systems and cold environments where Bacteroidetes is the major bacterial group. The abundance of sequences related to alphaproteobacteria and methanogenic populations likely reflects the importance of aerobic anoxigenic phothosynthesis and the cycling of one‐carbon compounds in the high altitude lake ecosystems. Geochemistry and microbial communities at Simba as well as those reported in the Licancabur summit lake provide evidence for sulfur‐rich environments but under different conditions. Those differences between neighboring mountain lake ecosystems highlight the effect of volcanic activity on microbial communities. The hypothetical ecosystem model described in this work provides a clue to follow the microbial community responses to geophysical environment coupled with rapid climate change.
The global carbon cycle in the Canadian Earth system model (CanESM1): Preindustrial control simulation
Authors: Christian J. R. , Arora V. K. , Boer G. J. , Curry C. L. , Zahariev K. , Denman K. L. , Flato G. M. , Lee W. G. , Merryfield W. J. , Roulet N. T. , Scinocca J. F.
Published: August 2010

The preindustrial carbon cycle is described for the Canadian Centre for Climate Modelling and Analysis Earth system model (CanESM1). The interhemispheric gradient of surface atmospheric CO2 concentration (xCO2) is reversed from the present day, with higher concentrations in the Southern Hemisphere, and southward interhemispheric transport by the ocean, estimated at 0.38 Pg C yr−1. The seasonal cycles of xCO2 and surface CO2 exchange are dominated by Northern Hemisphere terrestrial processes; the ocean contribution to CO2 flux is in phase with the larger terrestrial flux in the tropics and out of phase in the extratropics. Ocean processes dominate the relatively small Southern Hemisphere variability. Interannual variability of land carbon exchange is much larger than ocean exchange; both are comparable to results from previously published models with possibly larger variability in the terrestrial flux. Terrestrial net primary production (NPP) is determined largely by water availability at low latitudes, with temperature becoming more important at high latitudes. Temperature and moisture affect both NPP and heterotrophic respiration such that respiration effects tend to dampen the effect of fluctuations in NPP on CO2 exchange. Ocean CO2 flux variability is controlled by a variety of physical and biological processes with greater control by physical processes in the tropics and a larger biological contribution in the extratropics. Ocean CO2 flux is more strongly correlated with tropical sea surface temperature (SST) than terrestrial, but the variance associated with tropical SST is larger on land, in absolute terms, because of the much greater total variance of the land carbon flux. A novel hypothesis is advanced to explain how biological drawdown can cause recently upwelled water to be a net sink rather than source for atmospheric CO2. This process occurs over large areas of extratropical ocean and forms a natural sink for atmospheric CO2 that is potentially sensitive to both ocean acidification and anthropogenic perturbations of the aeolian iron flux.
Comparison of the open‐closed separatrix in a global magnetospheric simulation with observations: The role of the ring current
Authors: Rae I. J. , Kabin K. , Lu J. Y. , Rankin R. , Milan S. E. , Fenrich F. R. , Watt C. E. J. , Zhang J.‐C. , Ridley A. J. , Gombosi T. I. , Clauer C. R. , Tóth G. , DeZeeuw D. L.
Published: August 2010

The development of global magnetospheric models, such as Space Weather Modeling Framework (SWMF), which can accurately reproduce and track space weather processes has high practical utility. We present an interval on 5 June 1998, where the location of the polar cap boundary, or open‐closed field line boundary (OCB), can be determined in the ionosphere using a combination of instruments during a period encompassing a sharp northward to southward interplanetary field turning. We present both point‐ and time‐varying comparisons of the observed and simulated boundaries in the ionosphere and find that when using solely the coupled ideal magnetohydrodynamic magnetosphere‐ionosphere model, the rate of change of the OCB to a southward turning of the interplanetary field is significantly faster than that computed from the observational data. However, when the inner magnetospheric module is incorporated, the modeling framework both qualitatively, and often quantitatively, reproduces many elements of the studied interval prior to an observed substorm onset. This result demonstrates that the physics of the inner magnetosphere is critical in shaping the boundary between open and closed field lines during periods of southward interplanetary magnetic field (IMF) and provides significant insight into the 3‐D time‐dependent behavior of the Earth's magnetosphere in response to a northward‐southward IMF turning. We assert that during periods that do not include the tens of minutes surrounding substorm expansion phase onset, the coupled SWMF model may provide a valuable and reliable tool for estimating both the OCB and magnetic field topology over a wide range of latitudes and local times.
Satellite thermal observations of the Bezymianny lava dome 1993–2008: Precursory activity, large explosions, and dome growth
Authors: van Manen S. M. , Dehn J. , Blake S.
Published: August 2010

Fifteen years worth of Advanced Very High Resolution Radiometer (AVHRR) data is presented and used to quantitatively assess processes occurring at Bezymianny. This andesitic volcano is one of Kamchatka's most dangerous volcanoes with 16 eruptions in the last decade that have dispersed ash into North Pacific air routes. All known episodes of increased activity for which data were available were detected in band 3 (3.53–3.93 μm) AVHRR thermal data. Twenty‐three peaks can be seen in the data; nineteen peaks correspond to known explosions, while the remaining three peaks correspond to known phases of dome growth that were not believed to have been accompanied by explosive activity. Start and end dates of extrusive phases defined by the thermal data are presented. Repose times between phases of extrusion vary from four months to just over two and half years with an average of just less than a year. Using rank‐order statistics a ‘maximum’ time interval between consecutive explosions of 1288 ± 170 days is determined; this could serve as a cut‐off time for declaring the current dome‐growth activity over. The calculated cumulative erupted volume (0.28 km3) and time‐averaged extrusion rate (0.6 m3 s−1) from 1993 to 2008 corresponds to values found at Bezymianny from 1956 to 1976, showing that the satellite‐based methodology provides a good way of quantitatively assessing dome growth. Three different types of precursors to explosive behavior have been identified at Bezymianny: (1) values that cluster around the mode of the data set prior to explosion, potentially due to endogenous dome growth, (2) upward trends that commence 15–20 days prior to explosion and reach sensor saturation levels are due to significant extrusion, and (3) a gradual upward trend that starts 5 days prior to explosion, probably due to ramping up of extrusion. This work shows that retrospectively analyzing and modeling of a volcano's thermal signal provides increased insight into its characteristic behavior. The methods used in this paper can be used at other dome‐building volcanoes around the world. The insights presented here can be used to improve monitoring capabilities to aid in providing early warnings to large explosions at Bezymianny.
Acetone in the upper troposphere/lowermost stratosphere measured by the CARIBIC passenger aircraft: Distribution, seasonal cycle, and variability
Authors: Sprung Detlev , Zahn Andreas
Published: August 2010

Mass‐spectrometric measurements of acetone (CH3COCH3) have been performed monthly using a Lufthansa Airbus A340‐600 passenger aircraft between February 2006 and December 2008. In total, 106 measurement flights (4 per month) were conducted between Germany and South America, North America, South Asia, and East Asia. Here measurements collected between 33°N and 56°N in the upper troposphere (UT) and lowermost stratosphere (LMS) at 9–12 km altitude are analyzed. By integrating data collected at 12 ozonesonde stations, ozone concentrations measured on flight are translated into a representative (mixing‐based) altitude above the thermal tropopause. A strong seasonal variation of acetone occurs at the midlatitude tropopause with maxima of ∼900 parts per 1012 vol (pptv) in summer and minima of ∼200 pptv in midwinter. This seasonality propagates into the LMS in approximately 6 weeks with rapidly decreasing concentrations and increasing phase shifts reaching 2 km above the tropopause. Throughout the year, acetone and ozone are highly negatively correlated in the LMS with a mean linear correlation coefficient (R) of −0.93. This linear relationship marks the O3–acetone‐based extratropical tropopause mixing layer (exTL). A “stratospheric intrusion height of acetone” (Zacetone) is defined that concurs with the vertical depth of the O3–CO‐based exTL, namely, averaging ∼2.2 km but with slightly lower values in winter. Probability density functions (PDFs) and the course of the seasonal variation of acetone relative to the tropopause are interpreted regarding the in‐mixing and subsequent dispersion of acetone in the LMS.
A century of climate variability in central Dronning Maud Land, East Antarctica, and its relation to Southern Annular Mode and El Niño‐Southern Oscillation
Authors: Naik Sushant S. , Thamban Meloth , Laluraj C. M. , Redkar B. L. , Chaturvedi Arun
Published: August 2010

Stable isotope records of oxygen and hydrogen were studied from a 65 m long ice core retrieved from central Dronning Maud Land, East Antarctica, in order to reconstruct the coastal Antarctic climate variability during the last century and its relation to the Southern Annular Mode (SAM) and El Niño‐Southern Oscillation (ENSO). The δ18O records showed a significant relation to the SAM with a dominant ∼4 years variability, except during specific periods (1918–1927, 1938–1947, and 1989–2005) when ENSO teleconnection was established through the in‐phase relation between SAM and Southern Oscillation Index (SOI). The combined influence of ENSO and SAM was seen on surface air temperatures in this region mainly during the austral summer season from 1989 to 2005. Further, a significant relationship between δ18O and SAM was observed on a decadal scale, which overrides the intermittent influence of ENSO. Major shifts in the deuterium excess record were observed during periods of ENSO teleconnections, which support a shift in moisture source regions during the periods of stronger ENSO teleconnections. Surface air temperatures estimated using the δ18O‐T spatial slope for this region depicted a significant warming of 1°C for the past century. The study reveals that throughout the last century, SAM was the dominant mode of climatic variability in the coastal region of central Dronning Maud Land on a decadal scale.
Variations in surface ozone at Nainital: A high‐altitude site in the central Himalayas
Authors: Kumar Rajesh , Naja Manish , Venkataramani S. , Wild O.
Published: August 2010

Surface ozone measurements have been made for the first time at Nainital (29.37°N, 79.45°E, 1958 m amsl), a high‐altitude site in the central Himalayas, between October 2006 and December 2008. Diurnal variations in ozone do not show the daytime photochemical build‐up typical of urban or rural sites. The seasonal variation shows a distinct ozone maximum in late spring (May; 67.2 ± 14.2 ppbv) with values sometimes exceeding 100 ppbv and a minimum in the summer/monsoon season (August; 24.9 ± 8.4 ppbv). Springtime ozone values in the central Himalayas are significantly higher than those at another high‐altitude site (Mt. Abu) in the western part of India. Seasonal variations in ozone and the processes responsible for the springtime peak are studied using meteorological parameters, insolation, spatial and temporal classifications of air mass trajectories, fire counts, and simulations with a chemical transport model. Net ozone production over the Northern Indian Subcontinent in regionally polluted air masses is estimated to be 3.2 ppbv/day in spring but no clear build‐up is seen at other times of year. Annual average ozone values in regionally polluted air masses (47.1 ± 16.7 ppbv) and on high insolation days (46.8 ± 17.3 ppbv) are similar. Background ozone levels are estimated to be 30–35 ppbv. Regional pollution is shown to have maximum contribution (16.5 ppbv) to ozone levels during May–June and is about 7 ppbv on an annual basis, while the contribution of long‐range transport is greatest during January–March (8–11 ppbv). The modeled stratospheric ozone contribution is 2–16 ppbv. Both the trajectory analysis and the model suggest that the stratospheric contribution is 4–6 ppbv greater than the contribution from regional pollution. Differences in the seasonal variation of ozone over high‐altitude sites in the central Himalayas (Nainital) and western India (Mt. Abu) suggest diverse regional emission sources in India and highlight the large spatial and temporal variability in ozone over the Indian region.
Lateral Pressure Profiles in Lipid Membranes: Dependence on Molecular Composition
Authors: Ollila O. H. Samuli , Vattulainen Ilpo
Published: August 2010

The lateral pressure profile is one of the central quantities of lipid membranes, as it governs membrane elasticity and consequently the activation of certain membrane protein types such as mechanosensitive channels. Nonetheless, the understanding of the dependence of the pressure profile on molecular membrane composition is limited. In this review, we discuss the present understanding of pressure profiles in model membranes, discussing data from both computational and experimental approaches that have dealt with this complex physical observable. We consider pressure profiles in both single- and many-component lipid membranes, paying attention to effects due to polyunsaturated lipids, sterols, and anesthetics. The role of the pressure profile in membrane elasticity and membrane protein activation is given particular attention.
Multi-scale Simulations of Membrane Sculpting by N-BAR Domains
Authors: Yin Ying , Arkhipov Anton , Schulten Klaus
Published: August 2010

Cells contain membranes of various shapes, often formed with the help of cellular proteins. In particular, proteins of the BAR domain superfamily participate in various membrane sculpting processes, bending membranes through the concerted action of multiple BAR domains arranged in lattices. Despite extensive experimental studies, information on the dynamics of membrane bending and an explanation of the lattices' role are still lacking. Computational studies can furnish such information. Here we summarize recent work on the dynamics of membrane bending by N-BAR domains, a well-studied member of the BAR domain superfamily, at four levels of resolution: described by all-atom molecular dynamics, residue-based coarse graining (resolving single amino acids and lipid molecules), shape-based coarse graining (resolving overall protein and membrane shapes), and a continuum elastic membrane model. Simulations showed how the membrane curvature generated depends on the arrangement of N-BAR domains on the membrane surface. The lattice arrangements found to be optimal for producing high membrane curvature are composed of protein rows separated by ~5 nm, stability of the rows being maintained through electrostatic interactions between N-BAR domains. Formation of entire membrane tubes by lattices of N-BAR domains over time scales of ~200 μs was observed in coarse-grained simulations; an all-atom simulation of a 2.3 million atom system covering 0.3 μs complemented the coarse-grained simulations.
Continuum Electrostatics and Modeling of K+ Channels
Authors: Robertson Janice L. , Jogini Vishwanath , Roux Benoît
Published: August 2010

Continuum electrostatics applications of the PB equation, and the modified PB-V equation to include the influence of a transmembrane potential, have been reviewed with respect to three electrostatic features of K+ channels. These studies enable us to highlight how structural features of K+ channels are related to their function. Regarding permeation, the static field energy from the pore helices that surround the selectivity filter is key in providing a favorable stabilization for an ion inside the pore. The magnitude of the static field is more prominent for the closed state and reduces when the intracellular gate is opened. One of the most striking features is the large aqueous cavity located near the center of the bilayer, which helps reduce the electrostatic penalty of transferring an ion from bulk solution into the membrane. When the intracellular gate is open, the shape of the cavity is altered into an opened vestibule, which then further reduces the magnitude of the unfavorable reaction field. In the case of Kir channels, an additional cytoplasmic domain lengthens the ion permeation pathway more than two-fold. The extension of the low dielectric into the cytoplasm potentiates the static field inside the entire pore, indicating that residues have long-range electrostatic effects on ion behavior inside the channel. The cytoplasmic domain creates a very favorable environment for cations that has both electrostatic as well as specific molecular roles in regulating conductance and rectification properties. Finally, the transmembrane potential calculated by solution of the PB-V equation along the K+ channel pore is dependent on the channel state and corresponds well with experimental estimates of the voltage profile from permeation studies. Regarding voltage-gating, the PB-V provides a powerful route to assess the physical validity of proposed structural models. Calculation of the transmembrane potential along the voltage sensor of Kv1.2 shows that the key gating charges are localized near the region where the voltage gradient is the steepest, as if optimized for sensitivity. Altogether, the use of continuum electrostatics in the study of K+ channel structure has provided useful and robust analysis in understanding how these channels facilitate the permeation of K+ ions across the membrane and undergo voltage dependent activation.
Molecular Dynamics Studies of the Interactions Between Carbon Nanotubes and Biomembranes
Authors: Wallace E. Jayne , Sansom Mark S. P.
Published: August 2010

Molecular simulations can be used to explore possible of bionanotechnology applications of biomembranes. In this chapter we review the use of both atomistic and coarse grained simulations to explore interactions between carbon nanotubes (CNTs) and model biomembranes. Issues of parameterization of CNTs for simulations are of especial importance, and are likely to be an area of future methodological refinement. Simulations have been used to characterize the interactions of CNTs with detergent and lipid molecules, and with model lipid bilayers. Once embedded within a bilayer, CNTs may form transbilayer pores. Simulations have been used to explore the behaviour of water and ions in CNT pores, and to explore their potential as ‘nanosyringes' for injection across cell membranes.
Issues in Subgroup Analyses and Meta‐Analyses of Clinical Trials
Authors: BIGGER J. THOMAS
Published: August 2010

This commentary discusses two techniques commonly used to analyze clinical trials: subgroup analysis and meta‐analysis. Subgroup analysis is used to evaluate the consistency of a treatment across multiple groups, usually within a clinical trial. Subgroup analysis often is used to generate or test an hypothesis about risk factors or treatment responses. Meta‐analysis (overview) is used primarily to summarize data from several randomized clinical trials and to evaluate consistency among trials. Meta‐analysis is a formal way of summarizing the totality of information coming from well‐conducted randomized clinical trials. The use and limitations of these two techniques are discussed. (J Cardiovasc Electrophysiol, Vol. 14, pp. S6‐S8, September 2003, Suppl.)
Cost‐Effectiveness of the Implantable Cardioverter Defibrillator:
Authors: LYND LARRY D. , O'BRIEN BERNIE J.
Published: August 2010

Introduction: Implantable cardioverter defibrillator (ICD) therapy is indicated for patients at risk for sudden cardiac death (SCD) due to ventricular tachycardia (VT) or ventricular fibrillation (VF). The high relative cost of therapy with the ICD versus antiarrhythmic drugs has raised questions regarding its cost‐effectiveness. To address these questions, we review the literature on ICD cost‐effectiveness.

Methods and Results: MEDLINE and other databases were searched for articles published since 1980 reporting original data on the cost‐effectiveness of ICD versus drug therapy for patients at risk for SCD. Data on costs and life‐years were abstracted and studies grouped into decision analysis models and trial‐based analyses. Cost‐effectiveness ratios were inflated to 2002 US dollars. Thirteen economic studies were included in this review: 6 decision‐analytic models, 4 economic analysis alongside randomized controlled trials, and 1 observational study. Two additional studies evaluated the cost‐effectiveness of ICDs stratified by mortality risk. Studies varied in time horizon, and in all but one study ICD therapy was more costly than drug therapy. Early models assumed larger survival benefits than were observed in subsequent trials; therefore, ICDs appeared to be more cost‐effective (i.e., $28,000–$60,000 per life‐year gained). Three large clinical trial‐based studies estimated that the cost per life‐year gained was between $30,181 and $185,000. Stratified analyses show that patients at higher risk for mortality due to structural heart disease (e.g., left ventricular ejection fraction <35%) benefit more from ICD therapy, resulting in lower cost‐effectiveness ratios.

Conclusion: ICD therapy continues to evolve with changing methods of implantation and improving technology. Current evidence suggests that ICDs may be a cost‐effective option in patients at high risk for VT/VF. The cost‐effectiveness of ICD therapy for primary and secondary prevention of SCD depends upon patient characteristics that influence their prior risk of mortality. Further research on patient selection criteria and the measurement of health‐related quality of life is required. (J Cardiovasc Electrophysiol, Vol. 14, pp. S99‐S103, September 2003, Suppl.)
Translation of Clinical Trials into Clinical Practice:
Authors: CAMM A. JOHN
Published: August 2010

The “evidence base” for arrhythmology is enormous and highly variable in quality and relevance. Every day, more information becomes available from basic science, bedside research, randomized trials, structured registries, and clinical experience. It has become critically important to develop methods for collating and synthesizing all of these strands of evidence into a useful and applicable format. The guideline is an increasingly valuable tool for this purpose. Guidelines are constructed in a formal and approved manner such that the evidence is graded and combined to produce appropriately classified practical recommendations. Arrhythmology guidelines now must be funded, implemented, value tested, and regularly revised. (J Cardiovasc Electrophysiol, Vol. 14, pp. S9‐S14, September 2003, Suppl.)
Anterograde Slow Pathway Is Not the Same as Retrograde Slow Pathway Conducted in the Reverse Direction in Patients with Uncommon Atrioventricular Nodal Reentrant Tachycardia
Authors: Ooie Tatsuhiko , Tsuchiya Takeshi , Ashikaga Keiichi , Honda Toshihiro , Takahashi Naohiko
Published: August 2010

Introduction: The aim of this study was to examine the location of anterograde and retrograde slow pathways in 16 patients with uncommon atrioventricular nodal reentrant tachycardia (AVNRT), including the fast‐slow form in 10, slow‐slow form in 5, and both fast‐slow and slow‐slow forms in 1.

Methods and Results: Patients were divided into two groups according to the approach used for slow pathway ablation in the initial radiofrequency catheter ablation (RFCA): one approach used earliest atrial activation during tachycardia (ES group, n = 9), and the other used a slow potential during sinus rhythm (SP group, n = 7). When the initial RFCA failed to eliminate slow pathway conduction in the ES group, an additional RFCA guided by a slow potential was performed. The ratio of lengths from the His‐bundle region to the RFCA site and coronary sinus ostium (Abl/His‐CS ratio) and the ratio of amplitudes of atrial and ventricular potentials at the RFCA site (A/V ratio) were compared between the two groups. In the initial RFCA, retrograde slow pathway conduction was eliminated without impairment of anterograde slow pathway conduction in 8 (89%) patients from the ES group, and bidirectional slow pathway conduction was eliminated in 6 (86%) patients from the SP group. Residual anterograde slow pathway conduction that was preserved after the initial RFCA in 8 of 9 patients was eliminated by an additional slow potential‐guided RFCA. Both the Abl/His‐CS ratio (0.86 ± 0.07 vs 0.73 ± 0.11, P = 0.01) and A/V ratio (0.80 ± 0.31 vs. 0.14 ± 0.01, P < 0.001) were higher in the ES group than the SP group. The ratios for the residual anterograde slow pathway ablation in the ES group were similar to those in the SP group.

Conclusion: The results of this study suggest that the retrograde slow pathway runs more on the atrial side of the tricuspid valve annulus at the level of the coronary sinus ostium compared with the anterograde slow pathway, although both pathways run parallel or are fused in portions more proximal to the His bundle. (J Cardiovasc Electrophysiol, Vol. 14, pp. 722‐727, July 2003)
Heart Rate Versus Heart Rate Variability in Risk Prediction after Myocardial Infarction
Authors: ABILDSTROM STEEN Z. , JENSEN BERIT T. , AGNER ERIK , TORP‐PEDERSEN CHRISTIAN , NYVAD OLE , WACHTELL KRISTIAN , OTTESEN MICHAEL M. , KANTERS JØRGEN K. ,   BEAT Study Group
Published: August 2010

Heart Rate versus Heart Rate Variability.
Introduction: The aim of this study was to evaluate and compare heart rate and heart rate variability (HRV) in risk prediction after acute myocardial infarction (MI) and to evaluate the effect of beta‐blocker treatment on the prognostic performance of heart rate and HRV.

Methods and Results: Three hundred sixty‐six patients underwent 24‐hour Holter recording 1 to 6 days after an MI. HRV was expressed as the standard deviation of all normal‐to‐normal intervals. Left ventricular systolic function was evaluated using the wall motion index. Half of the patients were taking a beta‐blocker at the time of Holter recording. Mean follow‐up was 44 months (median 34) after MI. By the end of follow‐up, 82 patients had died. Mortality at 1 and 3 years was 12.5% and 22.6%, respectively. HRV, heart rate, wall motion index, number of ventricular premature beats per hour, and ventricular tachycardia were all significantly (P < 0.05) associated with mortality in univariate analysis, independent of beta‐blocker therapy. In multivariate Cox analysis, only heart rate, wall motion index, number of ventricular premature beats per hour, and age had independent prognostic value (P < 0.001). In any model, including heart rate, HRV had no predictive value.

Conclusion: The prognostic information of HRV is contained completely in heart rate, which carries prognostic information further than that of HRV. This result was independent of beta‐blocker treatment. (J Cardiovasc Electrophysiol, Vol. 14, pp. 168‐173, February 2003)
Novel Brugada SCN5A Mutation Leading to ST Segment Elevation in the Inferior or the Right Precordial Leads
Authors: POTET FRANCK , MABO PHILIPPE , LE COQ GUILLAUME , PROBST VINCENT , SCHOTT JEAN‐JACQUES , AIRAUD FABRICE , GUIHARD GILLES , DAUBERT JEAN‐CLAUDE , ESCANDE DENIS , LE MAREC HERVÉ
Published: August 2010

SCN5A Mutation and ST Segment Elevation in Inferior Leads. Mutations in the SCN5A gene can lead to the Brugada syndrome, a genetically inherited form of idiopathic ventricular fibrillation that has a characteristic ECG phenotype usually restricted to precordial leads V1–V3. We identified a novel G752R SCN5A missense mutation leading to various degrees of the Brugada ECG phenotype in members of a French family. In the proband, the G752R mutation produced ST segment elevation and prominent J wave in leads II, III, and aVF. In four other relatives, ST segment elevation in the right precordial but not in the inferior leads was observed either spontaneously or under flecainide challenge. Recombinant G752R mutant exhibited a markedly reduced Na+ current amplitude and a voltage shift in both activation and inactivation curves. The mutant was found in all affected but not in nonaffected family members. One additional gene‐carrier had an almost normal ECG (silent gene‐carrier). We provide genetic demonstration that Brugada ECG anomalies related to a unique SCN5A mutation can be observed either in the inferior or the right precordial leads. (J Cardiovasc Electrophysiol, Vol. 14, pp. 200‐203, February 2003)
Electrophysiologically Guided Pulmonary Vein Isolation During Sustained Atrial Fibrillation
Authors: MACLE LAURENT , JAÏS PIERRE , SCAVÉE CHRISTOPHE , WEERASOORIYA RUKSHEN , SHAH DIPEN C. , HOCINI MÉLÈZE , CHOI KEE‐JOON , RAYBAUD FLORENCE , CLÉMENTY JACQUES , HAÏSSAGUERRE MICHEL
Published: August 2010

Introduction: Sustained atrial fibrillation (AF) is frequently encountered during pulmonary vein (PV) isolation. The aim of this study was to evaluate the feasibility and safety of PV isolation during sustained AF.

Methods and Results: Thirty‐seven patients (30 men, age

54 ± 10 years

) underwent Lasso‐guided isolation of 87 PVs during sustained AF. Baseline PV electrogram patterns were classified into one of two types: organized, with consistent PV activation sequence; or disorganized, with constant variation of PV activation sequence. In disorganized activity, radiofrequency ablation was performed circumferentially around the Lasso while the earliest PV potential was targeted during organized activity. Complete left atrial (LA) to PV block during AF was identified by abolition or dissociation of all sharp potentials recorded within the vein. PV isolation then was verified during sinus rhythm. Baseline activation patterns of PV potential were organized in 32 PVs (37%) [more frequently in inferior veins than superior veins

(53% vs 26%, P = 0.01)

] and disorganized in 55 PVs (63%). In 59 of 87 PVs, isolation was begun and completed during AF. Radiofrequency ablation organized PV activation sequence in 75% prior to isolation. LA‐PV block was confirmed during sinus rhythm in 54 (92%) of 59 PVs. In 28 of 87 PVs, sinus rhythm was restored before complete LA‐PV block. Complete isolation was achieved in all 87 PVs without complications.

Conclusion: PV isolation can be effectively and safely performed during sustained AF, preceded in most cases by organization of PV electrogram activity. This strategy may be the preferred alternative to multiple intraprocedural cardioversions.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 255‐260, March 2003)
Effects of Glucose‐Induced Insulin Secretion on ST Segment Elevation in the Brugada Syndrome
Authors: NISHIZAKI MITSUHIRO , SAKURADA HARUMIZU , ASHIKAGA TAKASHI , YAMAWAKE NORIYOSHI , FUJII HIROYUKI , ARITA MASATAKA , ISOBE MITSUAKI , HIRAOKA MASAYASU
Published: August 2010

Introduction: ST segment elevation in patients with Brugada syndrome is known to fluctuate occasionally, influenced by multiple factors. Insulin has been shown to affect QT dispersion in healthy volunteers, as well as result in abnormality of ventricular repolarization in patients with congenital long QT syndrome.

Methods and Results: To assess a possible role of insulin in ST segment elevation in patients with Brugada syndrome, an oral glucose tolerance test (OGTT) was administered to 20 patients with Brugada syndrome and 20 normal patients without ST‐T changes as a control group. Plasma glucose and potassium levels, immunoreactive insulin concentration (IRI), and ST segment elevation and ST‐T wave changes on 12‐lead ECG during OGTT were analyzed. Augmentation (>1 mm) of ST elevation or morphologic changes in ST‐T waves were observed frequently in response to increased IRI during OGTT [15/20 cases (75%)] in patients with Brugada syndrome but in none of the patients in the control group [0/20 cases (0%),

P < 0.01

]. The changes returned to baseline 180 minutes after the glucose load in 9 of 15 patients. Patients who showed coved‐type ST elevation before the glucose load exhibited positive ECG changes more frequently than patients with saddleback‐type elevation or transiently normalized ST segment [8/8 cases (100%) vs 7/12 (58%),

P < 0.05

]. There was no significant difference between the two groups in terms of glucose, IRI, and potassium levels during OGTT.

Conclusion: The findings suggest that glucose‐induced insulin secretion is one of the contributing factors to fluctuation of ST segment elevation in patients with Brugada syndrome.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 243‐249, March 2003)
QT Dynamicity and Sudden Death After Myocardial Infarction:
Authors: CHEVALIER PHILIPPE , BURRI HARAN , ADELEINE PATRICE , KIRKORIAN GILBERT , LOPEZ MICHEL , LEIZOROVICZ ALAIN , ANDRÉ‐FOUËT XAVIER , CHAPON PHILIPPE , RUBEL PAUL , TOUBOUL PAUL
Published: August 2010

Introduction: The aim of this study was to determine whether impaired adaptation of the QT interval to changes in heart rate predicts sudden death after an acute myocardial infarction.

Methods and Results: The Groupe d'Etude du Pronostic de l'Infarctus du Myocarde (GREPI) trial was a prospective multicenter study designed to evaluate the long‐term outcome of myocardial infarction. QT dynamicity was evaluated in 265 patients by analyzing 24‐hour Holter recordings obtained 9 to 14 days after myocardial infarction. The linear regression slope of QT intervals measured to the apex and to the end of the T wave (QTe) plotted against RR intervals was calculated using a dedicated Holter algorithm. The value of QT/RR in predicting sudden death and total mortality was compared with those of ejection fraction, heart rate variability, and late potentials. Mean follow‐up was 81 ± 27 months. There were 73 deaths, of which 23 were sudden. Of all the parameters, an increased diurnal QTe/RR slope (>0.18) was the strongest independent predictor of sudden death (relative risk 6.07, confidence interval 1.48–24.95,

P = 0.01

).

Conclusion: Increased diurnal QTe dynamicity is independently predictive of sudden death among patients with myocardial infarction. This simple parameter may help to stratify risk and select patients who may benefit from antiarrhythmic prophylaxis.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 227‐233, March 2003)