bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients
Authors: Sherlock M , O’Sullivan E , Agha A , Behan L A , Owens D , Finucane F , Rawluk D , Tormey W , Thompson C J
Published: May 2009

Background

Hyponatraemia is a well-recognised complication of neurosurgical conditions, but the incidence and implications have not been well documented.

Objective

To define the incidence, pathophysiology and clinical implications of significant hyponatraemia in several neurosurgical conditions.

Methods

All patients admitted to the Irish National Neurosciences Centre at Beaumont Hospital, Dublin with traumatic brain injury, subarachnoid haemorrhage, intracranial neoplasm, pituitary disorders and spinal disorders who developed significant hyponatraemia (plasma sodium <130 mmol/l) from January 2002 to September 2003 were identified from computerised laboratory records. Data were collected by retrospective case note analysis.

Results

Hyponatraemia was more common in patients with pituitary disorders (5/81, 6.25%; p = 0.004), traumatic brain injury (44/457, 9.6%; p<0.001), intracranial neoplasm (56/355, 15.8%; p<0.001) and subarachnoid haemorrhage (62/316, 19.6%; p<0.001) than in those with spinal disorders (4/489, 0.81%). The pathophysiology of hyponatraemia was: syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 116 cases (62%) (31 (16.6%) drug-associated), hypovolaemic hyponatraemia in 50 cases (26.7%) (which included patients with insufficient data to assign to the cerebral salt-wasting group (CSWS)), CSWS in nine cases (4.8%), intravenous fluids in seven cases (3.7%) and mixed SIADH/CSWS in five cases (2.7%). Hyponatraemic patients with cerebral irritation had significantly lower plasma sodium concentrations (mean (SD) 124.8 (0.34) mmol/l) than asymptomatic patients (126.6 (0.29) mmol/l) (p<0.0001). Hyponatraemic patients had a significantly longer hospital stay (median 19 days (interquartile range (IQR) 12–28)) than normonatraemic patients (median 12 days (IQR 10.5–15)) (p<0.001).

Conclusions

Hyponatraemia is common in intracerebral disorders and is associated with a longer hospital stay. Cerebral irritation is associated with more severe hyponatraemia. SIADH is the most common cause of hyponatraemia and is often drug-associated.
Nicotine: does it have a role in the treatment of skin disease?
Authors: Ingram J R
Published: May 2009

Epidemiological evidence suggests that, although smoking is detrimental in some skin diseases, it is of benefit in others such as pemphigus and Behcet disease. Evidence that nicotine is of therapeutic value in selected skin diseases is limited to case reports. There has been renewed interest in nicotinic acetylcholine receptor agonists, such as nicotine, after the discovery of a “nicotinic anti-inflammatory pathway”. Nicotinic acetylcholine receptors exist in abundance in human skin, but it is unknown whether they exert an anti-inflammatory effect. Randomised controlled trials of nicotine preparations in those skin conditions that occur less often in smokers are necessary to establish the value of nicotine, if any, in the treatment of skin disease.
Respecting autonomy in young people
Authors: Beach R , Proops R
Published: May 2009

Paediatricians have a duty to protect the life and health of their patients and to respect their autonomy. Usually, there will be no conflict between these duties. Both children and parents want effective care and agree to the medical interventions that that are most likely to provide it. However, when children refuse or resist such interventions, it may be unclear when the duty to protect trumps the duty to respect. This is because children may have differing levels of autonomy, sometimes making them competent to make medical decisions for themselves and at other times not. Further, there may be conflict between the children and their parents in such circumstances. Children may refuse treatments that parents desire or vice versa. Sometimes paediatricians may agree with the child in the face of legal powers of parental guardianship. At other times they may agree with the parents, facing the prospect of forcing treatment on an unwilling child with potentially devastating psychological consequences. This paper will explore this potential ethical and legal minefield by evaluating some practical clinical cases based on the experiences of the primary author. It provides a range of examples of these different types of conflicts, including especially problematic “hard cases” that concern the withdrawal of life-sustaining treatment and child protection. The goal of the article is not simply to morally and legally outline the boundaries of such tensions in paediatric care. It also provides concrete advice about how they should best be resolved in everyday clinical practice.
α-CLUSTER STATES AND 4α-PARTICLE BOSE CONDENSATE IN 16O
Authors: FUNAKI Y. , YAMADA T. , HORIUCHI H. , RÖPKE G. , SCHUCK P. , TOHSAKI A.
Published: May 2009

In order to explore the 4α-particle condensate state in 16 O , we solve a full four-body equation of motion based on the 4α OCM (Orthogonality Condition Model) in a large 4α model space spanned by Gaussian basis functions. A full spectrum up to the [Formula: see text] state is reproduced consistently with the lowest six 0+ states of experimental spectrum. The [Formula: see text] state is obtained at 2 MeV above the 4α breakup threshold and has a dilute density structure, where the rms radius is more than 5 fm. The state has an appreciably large α condensate fraction 61 %, and a highly amount of [Formula: see text] components, both of which are strong pieces of evidence of the state being the 4α condensate state.
MICROSCOPIC WAVE FUNCTION OF ALPHA CONDENSATION
Authors: TOHSAKI AKIHIRO , FUNAKI YASURO , HORIUCHI HISASHI , RÖPKE GERD , SCHUCK PETER , YAMADA TAIICHI
Published: May 2009

We explain how to treat a microscopic wave function of α-condensation named THSR taking 3α-condensation as a typical example. The microscopic model, which fully takes into account the Pauli principle between all the constituent nucleons and effective inter-nucleon forces simultaneously, can play an important role in reproducing an α-gas-like nature thanks to α-condensation. We study its typical features by giving numerical results of the norm kernel for 3α-condensation.
THE APPLICATION OF THSR WAVE FUNCTION USING MONTE CARLO TECHNIQUE
Authors: ITAGAKI NAOYUKI , KIMURA MASAAKI , ITO MAKOTO , AOYAMA SHIGEYOSHI , HIRATA YUICHI
Published: May 2009

The condensed states of α-clusters or di-neutrons are studied by introducing a Monte Carlo technique for the description of the THSR (Tohsaki Horiuchi Schuck Röpke) wave function. The condensed state of five alpha particles is shown to be stable around the threshold energy even after taking into account the coupling effect between normal cluster states with 16 O +α configurations. Next, the mixing of di-neutron components in 8 He is studied. The ground state of 8 He corresponds to the sub-closed-shell configuration of the spin-orbit favored orbits (p3/2) for the neutrons, and the shell-model-like configuration is considered to be dominant. However, 8 He is a drip-line nucleus with a two-neutron separation energy of 2.1 MeV, and the di-neutron configuration, which is a characteristic feature of the weakly bound systems, mixes in the ground state. Finally, characteristic mechanism for the binding of clusters in neutron-rich nuclei (s2 bond) is discussed.
ALPHA CLUSTERING AND WEAK COUPLING IN THE 93Nb REGION
Authors: OHKUBO S.
Published: May 2009

From the viewpoint of a unified description of cluster structure and scattering in the A = 90 region, α scattering from 89 Y is investigated. α clustering and weak coupling in 93 Nb is discussed.
STAU-CATALYZED BIG-BANG NUCLEOSYNTHESIS AND NUCLEAR CLUSTER MODEL
Authors: KAMIMURA M. , KINO Y. , HIYAMA E.
Published: May 2009

Three-body cluster-model calculations are performed for the new types of big-bang nucleosynthesis (BBN) reactions that are calalyzed by a supersymmetric (SUSY) particle stau, a scalar partner of the tau lepton. If a stau has a lifetime ≳ 103s, it would capture a light element previously synthesized in standard BBN and form a Coulombic bound state. The bound state, an exotic atom, is expected to induce various reactions, such as (αX-) + d → 6 Li + X-, in which a negatively charged stau (denoted as X-) works as a catalyzer. Recent literature papers have claimed that some of these stau-catalyzed reactions have significantly large cross sections so that inclusion of the reactions into the BBN network calculation can change drastically abundances of some elements, giving not only a solution to the 6 Li -7 Li problem (calculated underproduction of 6 Li by ~ 1000 times and overproduction of 7 Li +7 Be by ~ 3 times) but also a constraint on the lifetime and the primordial abundance of the elementary particle stau. However, most of these literature calculations of the reaction cross sections were made assuming too naive models or approximations that are unsuitable for those complicated low-energy nuclear reactions. We use a few-body calculational method developed by the authors, and provides precise cross sections and rates of the stau-catalyzed BBN reactions for the use in the BBN network calculation.
ON THE STRUCTURE OF VORTICES IN THE INNER CRUST OF NEUTRON STARS
Authors: AVOGADRO P. , BARRANCO F. , BROGLIA R. A. , VIGEZZI E.
Published: May 2009

We study the structure of vortices and their interaction with nuclei in the inner crust of neutron stars. Vortices carry most of the angular momentum of the crust and according to some models are expected to play a key role in the phenomenon of glitches. The quantities of interest (the energy, the pairing gap, the density and the velocity field) are calculated in the framework of the Hartree-Fock-Bogoliubov (HFB) quantum mean field theory. We solve the HFB equations testing four different Skyrme functionals in the particle hole-channel and using a density-dependent contact interaction in the particle-particle channel. We find that the structure of a vortex is strongly affected by the presence of the nucleus, a fact which reflects itself in the density dependence of the pinning energy we calculate.
HYPERNUCLEAR PHYSICS STUDIED WITH THE SHELL AND CLUSTER MODELS
Authors: MOTOBA TOSHIO
Published: May 2009

Prospects of interesting hypernuclear structures are discussed for typical light p-shell systems with the cluster model application and also for the medium-heavy systems with shell-model applications. Corresponding to the recent experimental progress, importance of production reaction spectroscopy are emphasized.
STRUCTURE OF K-pp SYSTEM AND SUPER-STRONG NUCLEAR FORCE BY MIGRATING K- MESON: ITS THEORETICAL BACKGROUND
Authors: AKAISHI YOSHINORI , YAMAZAKI TOSHIMITSU
Published: May 2009

We have studied the structure of K-pp by solving this system in a variational method, starting from the ansatz that Λ* = Λ(1405) is a K-p quasi-bound state. The structure of K-pp reveals a molecular feature, namely, the K- in Λ* as an "atomic center" plays a key role in producing strong covalent bonding with the other proton. Deeply bound [Formula: see text] nuclear systems are formed by this "super-strong" nuclear force due to migrating real bosons [Formula: see text]a la Heitler-London-Heisenberg, which overcompensates the stiff nuclear incompressibility. Theoretical background of our phenomenological [Formula: see text] interaction is discussed, in connection with "decaying-state" description of kaonic nuclear clusters, concerning the effective [Formula: see text] interaction based on chiral SU (3) dynamics. It is of virtual importance to determine whether the Λ* mass is 1405 MeV or 1420 MeV. It is found that a K- absorption at rest in 3 He provides a testing ground better than that in 4 He .
FOUR-BODY CALCULATION FOR EXCITED STATES OF 4HE
Authors: HORIUCHI WATARU , SUZUKI YASUYUKI
Published: May 2009

Four-body calculations with explicitly correlated Gaussian bases are performed for excited states of 4 He . All the levels below E x =26 MeV are reproduced reasonably well using realistic potentials. An analysis is made to show how the [Formula: see text] state becomes a resonance but those having almost the same structure as this state in different spin-isospin channels are not observed as resonances. The calculation of spectroscopic amplitudes, nucleon decay widths, and spin-dipole transition strengths demonstrates that the [Formula: see text] state and the three lowest-lying negative-parity states with 0- and 2- have 3 H +p and 3 He +n cluster configurations, leading to the interpretation that these negative-parity states are the inversion-doublet partners of the [Formula: see text] state.
CLUSTER STRUCTURE STUDY BASED ON REALISTIC NUCLEAR FORCE: BRUECKNER-AMD
Authors: TOGASHI TOMOAKI , KATŌ KIYOSHI , MURAKAMI TAKAOMI
Published: May 2009

We propose a new approach of the Brueckner-AMD that makes the antisymmetrized molecular dynamics (AMD) calculations possible with realistic nuclear forces. In this method, we solve the Bethe-Goldstone equation and calculate the G-matrix for every nucleon pair described by wave packets of AMD correctly. We report the results of applications to light nuclei with the Brueckner-AMD.
TENSOR CORRELATION IN He AND Li ISOTOPES BASED ON TENSOR OPTIMIZED SHELL MODEL WITH UNITARY CORRELATION OPERATOR
Authors: MYO TAKAYUKI , KATŌ KIYOSHI , KIKUCHI YUMA , TOKI HIROSHI , IKEDA KIYOMI
Published: May 2009

We show the importance of the tensor correlation on the structures of He and Li isotopes. We develop the tensor optimized shell model (TOSM) to describe the strong tensor correlation of the nuclear force in nuclei. We investigate the exotic structures of 9,10,11 Li based on the 9 Li +n+n model where TOSM is used for 9 Li . The coupling between the tensor correlation in 9 Li and the extra two neutrons emerges Pauli-blocking, which increases the s2 component and develops the halo structure in 11 Li .

We further treat the short range repulsion of the nuclear force by the unitary correlation operator method (UCOM), while the tensor correlation is described by TOSM. We propose a new approach of TOSM+UCOM to describe nuclei from the nuclear force.
ANOMALOUSLY HINDERED E2 STRENGTHS IN 16,18C
Authors: ONG HOOI JIN , IMAI NOBUAKI , SUZUKI DAISUKE , IWASAKI HIRONORI , ONISHI TAKEO , SUZUKI MASARU , NAKAO TARO , ICHIKAWA YUICHI , OTA SHINSUKE , SAKURAI HIROYOSHI , TAKEUCHI SATOSHI , AOI NORI , BABA HIDETADA , BISHOP SHAWN , ISHIHARA MASAYASU , KUBO TOSHIYUKI , MOTOBAYASHI TOHRU , YANAGISAWA YOSHIYUKI , TOGANO YASUHIRO , KURITA KAZUO , KONDO YOSUKE , NAKAMURA TAKASHI , OKUMURA TOSHIFUMI
Published: May 2009

Lifetime measurement of the first excited 2+ state in 18 C was performed using an upgraded recoil shadow method to determine the electric quadrupole transition. The measured mean lifetime is 18.9 ± 0.9 (stat) ± 4.4 (syst) ps, which corresponds to a [Formula: see text] value of 4.3 ± 0.2 ± 1.0 e2 fm 4, or about 1.5 Weisskopf units. The mean lifetime of the first 2+ state in 16 C was remeasured to be about 18 ps, about four times shorter than the value reported previously. By incorporating the γ-ray angular distribution measured in this work into the previous measurement, this discrepancy has been explained. The observed transition strengths in 16,18 C are hindered compared to the empirical transition strengths, indicating that the anomalous hindered E2 strength observed in 16 C persists in 18 C .
STRUCTURE OF EXCITED STATES IN 14C
Authors: SUHARA TADAHIRO , KANADA-EN'YO YOSHIKO
Published: May 2009

Structure of excited states in 14 C were investigated with a method of the antisymmetrized molecular dynamics model. Variation with constraints on the quadrupole deformations (β, γ) was performed, and the configurations were superposed within the AMD framework. Above the ground band, three excited bands with the developed 3α-cluster core structures were suggested. Characteristic structures such as a triaxial structure and a linear-chain structure appear in the excited bands. It was found that the 10 Be correlation exists in the linear-chain structure.
DELAUNAY AND DIAMOND TRIANGULATIONS CONTAIN SPANNERS OF BOUNDED DEGREE
Authors: BOSE PROSENJIT , SMID MICHIEL , XU DAMING
Published: May 2009

Given a triangulation G, whose vertex set V is a set of n points in the plane, and given a real number γ with 0 < γ < π, we design an O(n)-time algorithm that constructs a connected subgraph G' of G with vertex set V whose maximum degree is at most 14 + ⌈2π/γ⌉. If G is the Delaunay triangulation of V, and γ = 2π/3, we show that G' is a t-spanner of V (for some constant t) with maximum degree at most 17, thereby improving the previously best known degree bound of 23. If G is a triangulation satisfying the diamond property, then for a specific range of values of γ dependent on the angle of the diamonds, we show that G' is a t-spanner of V (for some constant t) whose maximum degree is bounded by a constant dependent on γ. If G is the graph consisting of all Delaunay edges of length at most 1, and γ = π/3, we show that a modified version of the algorithm produces a plane subgraph G' of the unit-disk graph which is a t-spanner (for some constant t) of the unit-disk graph of V, whose maximum degree is at most 20, thereby improving the previously best known degree bound of 25.
EFFICIENT ALGORITHMS FOR THE OPTIMAL-RATIO REGION DETECTION PROBLEMS IN DISCRETE GEOMETRY WITH APPLICATIONS
Authors: WU XIAODONG
Published: May 2009

In this paper, we study several interesting optimal-ratio region detection (ORD) problems in d- D (d ≥ 3) discrete geometric spaces, which arise in high dimensional medical image segmentation. Given a d- D voxel grid of n cells, two classes of geometric regions that are enclosed by a single or two coupled smooth heighfield surfaces defined on the entire grid domain are considered. The objective functions are normalized by a function of the desired regions, which avoids a bias to produce an overly large or small region resulting from data noise. The normalization functions that we employ are used in real medical image segmentation. To our best knowledge, no previous results on these problems in high dimensions are known. We develop a unified algorithmic framework based on a careful characterization of the intrinsic geometric structures and a nontrivial graph transformation scheme, yielding efficient polynomial time algorithms for solving these ORD problems. Our main ideas include the following. We observe that the optimal solution to the ORD problems can be obtained via the construction of a convex hull for a set of O(n) unknown 2-D points using the hand probing technique. The probing oracles are implemented by computing a minimum s-t cut in a weighted directed graph. The ORD problems are then solved by O(n) calls to the minimum s-t cut algorithm. For the class of regions bounded by a single heighfield surface, our further investigation shows that the O(n) calls to the minimum s-t cut algorithm are on a monotone parametric flow network, which enables to detect the optimal-ratio region in the complexity of computing a single maximum flow.
Teaching skills and concepts for embedded systems design
Authors: Bertels Peter , D'Haene Michiel , Degryse Tom , Stroobandt Dirk
Published: May 2009

Smart devices are omnipresent today and the design of these embedded systems requires a multidisciplinary approach. It is important that students in electrical engineering and computer science learn these different aspects of embedded systems design. Our course on Complex Systems Design Methodology presents an overview of embedded systems design with a strong focus on the main concepts, preparing the students for more detailed follow-up courses on specific topics.

Imparting the theoretical concepts to the students is not sufficient, however. Hands-on sessions are indispensable for the students to acquire the necessary skills. In this article we present our approach for these hands-on sessions, which is to pose relatively small problems in separate sessions, each focusing on a single design aspect. Five years after the introduction of this new course at Ghent University, we can conclude that students not only like this course, but that their design skills have also improved by our new, aspect-focused, approach.
Use of discrete and soft processors in introductory microprocessors and embedded systems curriculum
Authors: Loo Sin Ming , Planting C. Arlen
Published: May 2009

This paper describes a sequence of two courses, starting with the teaching of introductory microprocessor concepts and extending to advanced embedded system programming. The introductory microprocessor course is taught using a soft processor with a field-programmable gate array as the development platform, a combination which allows the course to undergo continual improvement without being limited by fixed hardware. The second course builds on the foundation of the first course, with an emphasis on working with advanced devices, building complete embedded systems, and developing embedded programming skills with different targets. This paper describes the experiences gained from the first course, and the detailed plan for the second course. This paper also describes which tools to include and which to leave out in the learning process for this process to be most effective from both the students' and instructor's perspective.
Virtual microcontrollers
Authors: Sirowy Scott , Sheldon David , Givargis Tony , Vahid Frank
Published: May 2009

Embedded programming training today commonly involves numerous low-level details of a particular microcontroller. Such details shift focus away from higher-level structured embedded programming concepts. Thus, hard-to-break, unstructured programming habits are commonplace in the field. Yet structured embedded programming is becoming more necessary as embedded systems grow in complexity. We introduce a virtual microcontroller to address this problem. Freed from manufacturing or historical architectural issues, the virtual microcontroller contains the core features to support embedded programming training, and possesses an exceptionally clean interface to low-level features like timers, interrupt service routines, and UARTs. The virtual microcontroller can be mapped onto existing microcontrollers, or even onto FPGAs or a PC, providing more lab and book flexibility, at the expense of performance and size overhead. Most importantly, training can still use a bottom-up resource-aware approach, yet can focus more on structured embedded programming concepts.
Non-expert construction of customized embedded systems to enhance STEM curricula
Authors: Phalke Anuradha , Biller Miria , Lysecky Susan , Harris Christopher
Published: May 2009

We present an interactive platform to enhance STEM education through project-based activities that complement the existing curriculum, while drawing on problem solving skills and team work. The addition of hands-on projects is intended not only to reinforce the various concepts learnt through normal class readings and discussion, but also make these topics multi-dimensional by enabling students to apply these principles in their everyday surroundings. The types of courses that can take advantage of the eBlock platform range from middle school math and science classes to university level engineering courses. In this paper we present the eBlocks platform which can be utilized to implement a wide variety of projects without requiring users to have programming or electronics experience. Specifically, we summarize the preliminarily usability results, discuss possible applications of the eBlock platform for various age groups, and introduce the initial curriculum development for middle school audiences.
Multi-processor programming in the embedded system curriculum
Authors: Hansson Andreas , Akesson Benny , van Meerbergen Jef
Published: May 2009

Teaching embedded system design is challenging, as the subject covers a wide range of aspects, and also involves skills that students do not learn from a text book. As a result, hands-on projects, with varying degree of complexity, are the most common approach in existing courses. Traditionally, the projects are limited to uni-processor systems, and do not address the complications involved in parallelising applications and mapping them to multi-processor systems.

In this paper, we describe a two-year-old embedded systems design course given at Eindhoven University of Technology. In the course, groups of four students are faced with the problem of putting an embedded JPEG decoder on the market within one semester. The starting point is a decoder written in sequential C and an embedded multiprocessor system, running on an FPGA. We describe the ideas and organisation of the course, and give examples of what challenges the students, as well as the instructors, are faced with. We exemplify results and give suggestions to those wishing to teach embedded multi-processor programming elsewhere.
Design and development of a wireless sensor model for vehicular area networks
Authors: Umesh P. , Varaprasad G.
Published: May 2009

Vehicular area network provides vehicle-to-vehicle, vehicle-to-infrastructure, and vehicle-to-person communications. Its aim is to increase the road safety and transport facility efficiency. It also provides a ubiquitous wireless environment for the end users. The vehicle area network is considered as one of the major applications for wireless networks. Here, each vehicle has a unique identifier and eavesdropper to accumulate the locations of vehicles. If the vehicle changes its pseudonym from time to time, then the long-term tracking is to be avoided. The proposed model automatically monitors the flow of vehicles and sends the data to the control room via gateway nodes. It uses number of sensors to reduce the traffic at important junctions while forwarding the vehicle from one place to another.
NetTopo
Authors: Shu Lei , Wu Chun , Zhang Yan , Chen Jiming , Wang Lei , Hauswirth Manfred
Published: May 2009

Simulators are needed for testing algorithms of wireless sensor networks (WSNs) for large scale scenarios. Deploying real WSN testbed provides a more realistic testing environment, and allows users to get more accurate test results. However, deploying real testbed is highly constrained by the available budget when the test needs a large scale WSN environment. By leveraging the advantages of both simulators and real testbed, an approach that integrates simulation environment and testbed can effectively solve both scalability and accuracy issues. Hence, the simulation of virtual WSN, the visualization of real testbed, and the interaction between simulated WSN and testbed emerge as three key challenges. In this paper, we present NetTopo for providing both simulation and visualization functions to assist the investigation of algorithms in WSNs. Two case studies are described to prove the effectiveness of NetTopo.
Bioimage Informatics for Experimental Biology
Authors: Swedlow Jason R. , Goldberg Ilya G. , Eliceiri Kevin W. ,   the OME Consortium
Published: May 2009

Over the past twenty years there have been great advances in light microscopy with the result that multidimensional imaging has driven a revolution in modern biology. The development of new approaches of data acquisition is reported frequently, and yet the significant data management and analysis challenges presented by these new complex datasets remain largely unsolved. As in the well-developed field of genome bioinformatics, central repositories are and will be key resources, but there is a critical need for informatics tools in individual laboratories to help manage, share, visualize, and analyze image data. In this article we present the recent efforts by the bioimage informatics community to tackle these challenges, and discuss our own vision for future development of bioimage informatics solutions.
A Physical Chemist's Expedition to Explore the World of Membrane Proteins
Authors: Chan Sunney I.
Published: May 2009

Despite growing up amid humble surroundings, I ended up receiving an excellent education at the University of California at Berkeley and postdoctoral training at Harvard. My academic career at Caltech was shaped by serendipity, inspirational colleagues, and a stimulating research environment, as well as smart, motivated students and postdocs who were willing to join my search for molecular understanding of complex biological systems. From chemical physics I allowed my research to evolve, beginning with the application of NMR to investigate the base stacking of nucleic acid bases in solution, the dynamic structure of membranes, and culminating with the use of various forms of spectroscopy to elucidate the structure and function of membrane proteins and the early kinetic events in protein folding. The journey was a biased random walk driven by my own intellectual curiosity and instincts and by the pace at which I learned biochemistry from my students and postdocs, my colleagues, and the literature and through osmosis during seminars and scientific meetings.
Persistence of Hepatitis C RNA in Liver Allografts Is Associated with Histologic Progression Independent of Serologic Viral Clearance
Authors: Ghabril M. , Dickson R. C. , Krishna M. , Lloyd R. , Aranda-Michel J. , Keaveny A. , Satyanarayana R. , Bonatti H.
Published: May 2009

Background. Hepatitis C virus (HCV) nondetectability in the liver may predict a sustained viral response (SVR) in patients with an end of treatment response. HCV RNA can be detected in liver tissue by in situ hybridization (ISH).Aim. To determine if HCV nondetectability in liver allografts by ISH can predict SVR in patients who cleared virus serologically on treatment.Methods. Twenty five patients with undetectable serum HCV on Interferon/Ribavirin therapy for HCV recurrence post liver transplant (LT) were studied. All had biopsies at 4 months post LT (baseline) and follow up with HCV ISH analysis performed.Results. 10 were ISH positive (group 1); 15 were ISH negative (group 2). Groups 1 and 2 had similar patient, donor, and viral characteristics at LT, as well as treatment duration at the time of the ISH assayed liver biopsy (13±16versus10±4monthsP= .24). However, group 1 had longer total treatment duration (24±10versus14±5months,P= .001). Eight (80%) group 1 and 9 (60%) group 2 patients achieved SVR. Mean grade and stage (modified Ishak score) were similar at 4 months, however, group 1 had higher grade (3±1.7versus1.6±1.3,P= .039) and stage (1.4±1.4versus0.5±0.6,P= .084) on the ISH assayed biopsy, after similar post LT intervals (23±10versus24±12months,P= .91).Conclusion. Allograft HCV ISH nondetectability does not predict SVR in treatment responsive HCV recurrence, but is associated with less severe histologic disease.
Selection and Penalty Strategies for Genetic Algorithms Designed to Solve Spatial Forest Planning Problems
Authors: Thompson Matthew P. , Hamann Jeff D. , Sessions John
Published: May 2009

Genetic algorithms (GAs) have demonstrated success in solving spatial forest planning problems. We present an adaptive GA that incorporates population-level statistics to dynamically update penalty functions, a process analogous to strategic oscillation from the tabu search literature. We also explore performance of various selection strategies. The GA identified feasible solutions within 96%, 98%, and 93% of a nonspatial relaxed upper bound calculated for landscapes of 100, 500, and 1000 units, respectively. The problem solved includes forest structure constraints limiting harvest opening sizes and requiring minimally sized patches of mature forest. Results suggest that the dynamic penalty strategy is superior to the more standard static penalty implementation. Results also suggest that tournament selection can be superior to the more standard implementation of proportional selection for smaller problems, but becomes susceptible to premature convergence as problem size increases. It is therefore important to balance selection pressure with appropriate disruption. We conclude that integrating intelligent search strategies into the context of genetic algorithms can yield improvements and should be investigated for future use in spatial planning with ecological goals.
Common Fixed Point Theorems for Weakly Compatible Pairs on Cone Metric Spaces
Authors: Jungck G. , Radenovic S. , Radojevic S. , Rakocevic V.
Published: May 2009

We prove several fixed point theorems on cone metric spaces in which the cone does not need to be normal. These theorems generalize the recent results of Huang and Zhang (2007), Abbas and Jungck (2008), and Vetro (2007). Furthermore as corollaries, we obtain recent results of Rezapour and Hamlborani (2008).
Growth of Pd‐Filled Carbon Nanotubes on the Tip of Scanning Probe Microscopy
Authors: Sakamoto Tomokazu , Chiu Chien-Chao , Tanaka Kei , Yoshimura Masamichi , Ueda Kazuyuki
Published: May 2009

We have synthesized Pd‐filled carbon nanotubes (CNTs) oriented perpendicular to Si substrates using a microwave plasma‐enhanced chemical vapor deposition (MPECVD) for the application of scanning probe microscopy (SPM) tip. Prior to the CVD growth, Al thin film (10 nm) was coated on the substrate as a buffer layer followed by depositing a 5 ~ 40 nm‐thick Pd film as a catalyst. The diameter and areal density of CNTs grown depend largely on the initial Pd thickness. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images clearly show that Pd is successfully encapsulated into the CNTs, probably leading to higher conductivity. Using optimum growth conditions, Pd‐filled CNTs are successfully grown on the apex of the conventional SPM cantilever.
Autonomic Testing in Functional Gastrointestinal Disorders: Implications of Reproducible Gastrointestinal Complaints during Tilt Table Testing
Authors: Safder Shaista , Chelimsky Thomas C. , O'Riordan Mary Ann , Chelimsky Gisela
Published: May 2009

Background: The pathophysiology of functional abdominal pain (FAP) is unknown. The upright portion of a tilt table test triggers typical symptoms in certain children. Aim: To compare the pathophysiology and treatment response of children with FAP whose gastrointestinal symptoms (GI) were replicated (RGI) by tilt table testing (TTT) to those in whom TTT did not have this effect (NRGI).Methods: An IRB-approved retrospective review of the autonomic laboratory database identified all children tested for GI complaints. We compared results of TTT, Valsalva maneuver, deep breathing and the axon reflex sweat test. Overall treatment response and that specific to fludrocortisone was ranked from 1 to 5, with 1 “much worse,” 3 “neutral,” and 5 “much better.”Results: 32/76 identified children had reproducible symptoms on TTT (RGI) and 44 did not (NRGI). The RGI group was younger, had a shorter duration of symptoms, more postural tachycardia syndrome (POTS) and benefited more from fludrocortisone (73% in RGI vs. 25% in NRGI).Conclusion: Dividing patients with FAP according to the effect of TTT on their symptoms appears to delineate 2 fundamentally different groups, with potentially different pathophysiologies and treatment responses. A prospective study is needed.
FatalPlasmodium falciparum,Clostridium perfringens, andCandida spp.Coinfections in a Traveler to Haiti
Authors: Genrich Gillian L. , Bhatnagar Julu , Paddock Christopher D. , Zaki Sherif R.
Published: May 2009

Malaria is one of the most common causes of febrile illness in travelers. Coinfections with bacterial, viral, and fungal pathogens may not be suspected unless a patient fails to respond to malaria treatment. Using novel immunohistochemical and molecular techniques,Plasmodium falciparum,Clostridium perfringens, andCandida spp.coinfections were confirmed in a German traveler to Haiti.Plasmodium falciparum-induced ischemia may have increased this patient's susceptibility toC. perfringensand disseminated candidiasis leading to his death. When a patient presents withP. falciparumand shock and is unresponsive to malaria treatment, secondary infections should be suspected to initiate appropriate treatment.
Improved Patient Survival Using a Modified Resuscitation Protocol for Out-of-Hospital Cardiac Arrest
Authors: Garza Alex G. , Gratton Matthew C. , Salomone Joseph A. , Lindholm Daniel , McElroy James , Archer Rex
Published: May 2009

Background—

Cardiac arrest continues to have poor survival in the United States. Recent studies have questioned current practice in resuscitation. Our emergency medical services system made significant changes to the adult cardiac arrest resuscitation protocol, including minimizing chest compression interruptions, increasing the ratio of compressions to ventilation, deemphasizing or delaying intubation, and advocating chest compressions before initial countershock.

Methods and Results—

This retrospective observational cohort study reviewed all adult primary ventricular fibrillation and pulseless ventricular tachycardia cardiac arrests 36 months before and 12 months after the protocol change. Primary outcome was survival to discharge; secondary outcomes were return of spontaneous circulation and cerebral performance category. Survival of out-of-hospital arrest of presumed primary cardiac origin improved from 7.5% (82 of 1097) in the historical cohort to 13.9% (47 of 339) in the revised protocol cohort (odds ratio, 1.80; 95% confidence interval, 1.19 to 2.70). Similar increases in return of spontaneous circulation were achieved for the subset of witnessed cardiac arrest patients with initial rhythm of ventricular fibrillation from 37.8% (54 of 143) to 59.6% (34 of 57) (odds ratio, 2.44; 95% confidence interval, 1.24 to 4.80). Survival to hospital discharge also improved from an unadjusted survival rate of 22.4% (32 of 143) to 43.9% (25 of 57) (odds ratio, 2.71; 95% confidence interval, 1.34 to 1.59) with the protocol. Of the 25 survivors, 88% (n=22) had favorable cerebral performance categories on discharge.

Conclusions—

The changes to our prehospital protocol for adult cardiac arrest that optimized chest compressions and reduced disruptions increased the return of spontaneous circulation and survival to discharge in our patient population. These changes should be further evaluated for improving survival of out-of-hospital cardiac arrest patients.
Cardiac Microvascular Pathology in Fabry Disease
Authors: Thurberg Beth L. , Fallon John T. , Mitchell Richard , Aretz Thomas , Gordon Ronald E. , O'Callaghan Michael W.
Published: May 2009

Background—

In classic Fabry patients, accelerated coronary atherosclerosis and left ventricular hypertrophy manifest in the fourth decade; however, signs of cardiovascular disease also are observed later in life in “cardiac variant” patients and symptomatic female heterozygotes. These disturbances are caused by globotriaosylceramide (GL-3) accumulation in the heart resulting from lysosomal α-galactosidase A deficiency.

Methods and Results—

We analyzed pretreatment and posttreatment endomyocardial biopsies from 58 Fabry patients enrolled in a 5-month, phase 3, double-blind, randomized, placebo-controlled trial, followed by a 54-month open-label extension study of recombinant human α-galactosidase A. Baseline evaluations revealed GL-3 deposits in interstitial capillary endothelial cells and large, laminated inclusions within cardiomyocytes. In this study, we evaluated microvascular GL-3 clearance; no clearance of GL-3 was observed in the cardiomyocytes during this trial. Five months of recombinant human α-galactosidase A treatment in the phase 3 trial resulted in complete microvascular clearance of GL-3 from 72% of treated patients compared with only 3% of placebo patients (
P
<0.001). The placebo group achieved similar results after 6 months of treatment in the open-label trial. In addition, the capillary endothelium remained free of GL-3 for up to 60 months in 6 of 8 patients who consented to an end-of-study biopsy.

Conclusions—

The findings suggest that long-term treatment with recombinant human α-galactosidase A may halt the progression of vascular pathology and prevent the clinical manifestations of atherosclerotic disease. This histopathological study should be a useful guide for clinicians and pathologists who diagnose and follow Fabry patients.
Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease
Authors: Gutiérrez Orlando M. , Januzzi James L. , Isakova Tamara , Laliberte Karen , Smith Kelsey , Collerone Gina , Sarwar Ammar , Hoffmann Udo , Coglianese Erin , Christenson Robert , Wang Thomas J. , deFilippi Christopher , Wolf Myles
Published: May 2009

Background—

Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD.

Methods and Results—

In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23;
P
=0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23;
P
=0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification ≥100 versus <100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment.

Conclusions—

FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.
Cytochrome P450 Genetic Polymorphisms and the Response to Prasugrel
Authors: Mega Jessica L. , Close Sandra L. , Wiviott Stephen D. , Shen Lei , Hockett Richard D. , Brandt John T. , Walker Joseph R. , Antman Elliott M. , Macias William L. , Braunwald Eugene , Sabatine Marc S.
Published: May 2009

Background—

Both clopidogrel and prasugrel require biotransformation to active metabolites by cytochrome P450 (CYP) enzymes. Among persons treated with clopidogrel, carriers of reduced-function
CYP2C19
alleles have significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse cardiovascular events. The effect of CYP polymorphisms on the clinical outcomes in patients treated with prasugrel remains unknown.

Methods and Results—

The associations between functional variants in CYP genes, plasma concentrations of active drug metabolite, and platelet inhibition in response to prasugrel were tested in 238 healthy subjects. We then examined the association of these genetic variants with cardiovascular outcomes in a cohort of 1466 patients with acute coronary syndromes allocated to treatment with prasugrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 trial. Among the healthy subjects, no significant attenuation of the pharmacokinetic or the pharmacodynamic response to prasugrel was observed in carriers versus noncarriers of at least 1 reduced-function allele for any of the CYP genes tested (
CYP2C19
,
CYP2C9
,
CYP2B6
,
CYP3A5
, and
CYP1A2
). Consistent with these findings, in subjects with acute coronary syndromes treated with prasugrel, no significant associations were found between any of the tested CYP genotypes and risk of cardiovascular death, myocardial infarction, or stroke.

Conclusions—

Common functional CYP genetic variants do not affect active drug metabolite levels, inhibition of platelet aggregation, or clinical cardiovascular event rates in persons treated with prasugrel. These pharmacogenetic findings are in contrast to observations with clopidogrel, which may explain, in part, the different pharmacological and clinical responses to the 2 medications.
Impact of Early Onset Obesity and Hypertension on the Unfolded Protein Response in Renal Tissues of Juvenile Sheep
Authors: Sharkey Don , Fainberg Hernan P. , Wilson Vicky , Harvey Emma , Gardner David S. , Symonds Michael E. , Budge Helen
Published: May 2009

Childhood obesity has reached epidemic proportions. Obesity is an independent risk factor for the development of end-stage renal disease. Endoplasmic reticulum stress and subsequent activation of the unfolded protein response (UPR) are implicated in the development of adipose tissue dysregulation and type 2 diabetes mellitus in obesity. The present study explored the impact of adolescent-onset obesity on the UPR after obesity-related hypertension and nephropathy, using an ovine model in which obesity was induced by increased food intake and reduced activity. Obese young adults had a higher mean arterial pressure (lean, 89.6±1.7 mm Hg versus obese, 101±3.0 mm Hg;
P
<0.01) and greater sensitivity to low physiological doses of angiotensin II. Obesity increased the glomerular area and was associated with activation of the UPR in renal cells with a greater abundance of glucose-regulated protein 78, C/EBP homologous protein, Bax, phosphorylated c-Jun amino-terminal kinase, and activating transcription factor 6 (all
P
<0.05). In addition, there was a marked upregulation of proinflammatory genes, most notably those involved in macrophage signaling. Reactive oxygen species production and handling were also perturbed in obese adults. Renal endoplasmic reticulum stress was positively correlated with macrophage content (
r
=0.83;
P
<0.001), phosphorylated c-Jun amino-terminal kinase (
r
=0.73;
P
<0.01), and adiposity (
r
=0.71;
P
<0.01). In conclusion, adolescent-onset, obesity-related renal endoplasmic reticulum stress was associated with activation of the UPR, apoptosis, and inflammation, potentially increasing the associated renal damage observed in young adults. The UPR may prove to be a useful therapeutic target for the treatment and prevention of obesity-related nephropathy and associated hypertension, thereby reducing the burden of end-stage renal disease.