bluuebunny/crossref_metadata_2025 huggingface dataset:
Current State of Clinical and Morphological Features in Human NCL
Authors: Goebel Hans H , Wisniewski Krystyna E.
Published: July 2010

The neuronal ceroid lipofuscinoses (NCL) are large group of autosomal recessive lysosomal storage disorders with both enzymatic deficiency and structural protein dysfunction. Previously, diagnosis of (NCL) was based on age at onset clinicopathological (C‐P) findings described 4 forms, classified as infantile (INCL) (2), late‐infantile (LINCL) (5), juvenile (JNCL) (6), and adult (ANCL) most patients with NCL have progressive ocular and cerebral dysfunvtion, including cognitive/motor dysfunction and uncontrolled seizures. After reviewing 520 patients with NCL, we found that about 104 (20%) did not fit this classification of NCL With further research, 4 additional forms have been recognized: Finnish (13), Gypsy/Indian (14), Turkish (15)—varoamts of LINCL, and Northern epilepsy (16), also known as progressove epilepsy with mental retaedation. These eight NCL forms resulted from 151 diffeent mutations in genes CLN1 to CLN8 causing different phenotypes (http://www.ucl.ac.uk/nclhttp://www.ucl.ac.uk/ncl). The genes CLN1 and CLN2 encode lysosomal palmitoyl protein diagnosis of NCL is based on clinicopathological (c‐p) findings, enzymatic assay, and molecular genetic testing. Ultrastructural studies must be performed to confirm the presence and nature of lysosomal storage material (fingerprint or curvilinear profiles presence and nature of lysosomal storage or granular osmiophilic deposits) before doing biochemical testing. Pheno/genotypic correlation studies are discussed.
Human Immunodeficiency Virus Infection of the Brain: Pitfalls in Evaluating Infected/Affected Cell Populations
Authors: Bissel Stephanie J. , Wiley Clayton A.
Published: July 2010

Monocyte/macrophages and CD4 T‐cells are the primary hematopoietic targets of productive HIV infection. In the brain, potential cellular targets for HIV infection include perivascular and parenchymal macrophages/microglia, oligodendrocytes, endothelia, neurons, and astrocytes. We examine evidence of productive and non‐productive infection for each cell type in the brains of HIV‐infected patients with and without HIV encephalitis. Despite the voluminous literature and substantial experimental effort over the past two decades, evidence for productive infection of any brain cell other than macrophages is left wanting.
The Role of the Extracellular Matrix in Angiogenesis in Malignant Glioma Tumors
Authors: Wang Dongyan , Anderson Joshua C. , Gladson Candece L.
Published: July 2010

Angiogenesis is a promising target for the development of effective strategies for the treatment of malignant brain tumors in that it has the potential to starve large tumors and prevent the regrowth of residual margins. Two critical steps in angiogenesis, the proliferation of activated endothelial cells and their migration into the perivascular space (sprouting), require adherence of the endothelial cells to the extracellular matrix (ECM). Thus, the availability of the appropriate ligands within the ECM contributes to the regulation of angiogenesis. In addition, several components of the ECM can act through other mechanisms to further promote angiogenesis or inhibit it. Current evidence suggests that the regulation of angiogenesis is a dynamic process in which the endothelial cells can promote angiogenesis by secreting proteases that remodel the ECM, tumor cells can further promote angiogenesis by secreting ECM components and actively remodeling their environment, and stromal cells may respond to angiogenesis associated with tumors and inflammatory reactions by secreting inhibitory molecules. Here, we provide a critical review of the protein and proteoglycan components of the ECM that have been implicated in angiogenesis with an emphasis on their role in promoting or inhibiting angiogenesis in brain tumors.
Neuropathological Findings in 9 Cases of Listeria Monocytogenes Brain Stem Encephalitis
Authors: Antal Ellen‐Ann , Løberg Else‐Marit , Dietrichs Espen , Mæhlen Jan
Published: July 2010

Brain stem encephalitis is a particular manifestation of infection with the bacterium Listeria monocytogenes. Here, we present the neuropathological findings in 9 such cases. In the brain stem, the inflammatory infiltrates were located predominantly within nuclei and tracts of cranial nerves innervating the oropharynx. These findings support the hypothesis that the food‐borne bacterium Listeria monocytogenes invades the brain stem along cranial nerves.
Inflicted Traumatic Brain Injury in Infants and Young Children
Authors: Case Mary E.
Published: July 2010

This article will discuss the subject of inflicted or abusive head injury in infants and young children. Inflicted neurotrauma is a very common injury and a frequent problem in attempting to distinguish between inflicted and accidental injury. Inflicted head injury occurs usually in the home in the presence of the individual who has inflicted the injury outside the view of unbiased witnesses. Distinguishing between inflicted and accidental injury may be dependent upon the pathological findings and consideration of the circumstances surrounding the injury.

The most common finding in an inflicted head injury is the presence of subdural hemorrhage. Subdural hemorrhage may occur in a variety of distributions and appearances. The natural history of subdural bleeding and the anatomy of the “subdural” will be considered. The anatomy of the dura and its attachment to the skull and to the arachnoid determines how subdural bleeding evolves into the cleaved dural border cell layer and as well as how bridging veins are torn and anatomically where bleeding will occur. Different biomechanical mechanisms result in different distributions of subdural blood and these differences will be discussed.
L'Inde présentée par elle‐même
Authors: Vatsyayan Kapila
Published: July 2010

Dans le premier article de ce dossier concernant le Festival de l'Inde, qui s'est tenu à Londres du mois de mars jusqu'au mois de novembre 1982, Kapila Vatsyayan, distinguée historienne de l'art et de la danse indiens, donne un bref aperçu des idées et du matériel qui ont servi de base à un noyau central de cinq expositions. Ce fut elle‐même qui planta la graine de « l'arbre majestueux » qu'allait devenir cette longue série d'expositions réparties sur neuf mois. Cela est particulièrement vrai de l'exposition intitulée In the image of man (« A l'image de l'homme »), qui fut une expérience totalement novatrice, tant par sa conception que par sa présentation. Les articles des deux Australiens résidant au Royaume‐Uni qui ont participé à l'exécution du projet, l'un étant chargé de réunir les objets, l'autre de les présenter, sont donc consacrés à cette exposition unique en son genre. L'ensemble des expositions est brièvement passé en revue par le rédacteur en chef; son article reprend en grande partie des interviews et des discussions avec les organisateurs londoniens de l'exposition.
Trinidad de Cuba: histoire, romantisme et combats
Authors: Arjona Marta
Published: July 2010

Comment mobiliser les musées pour rendre vivante l'histoire d'une ville des Caraïbes dont l'existence remonte à près de cinq siècles? Voici la réponse de Marta Arjona, directrice du Patrimoine culturel de Cuba et membre du Conseil exécutif de l'ICOM.
Les musées et les femmes au Portugal: brève histoire d'une relation florissante
Authors: Texeira Madalena Braz
Published: July 2010

Les relations entre les femmes et les musées, au Porttugal sent beaucoup plus anciennes qu'on ‘potrraot l'imaginer puisque, aussi parad’ que cela puisse paraître, elles remontent trois cents ans avant que le premier ée portant ce nom ait été créEé dans ce pays. L'auteur, titulaire d'un M. A. en muséologie, a écrit Os primusous criados ern Portugal [Les premiers musées créés au Portugal], 1984 et dirige actuellement le Muséee national du costume de Lisbonne. On pout la joindre à l'adresse suivante: Musep National do Traje, Parque do monteiro Mor. Largo Julio de Castilho, Lumior, Lisbonne (Portugal).
Un code de déontologie pour les musées américains
Authors: Macdonald Robert R.
Published: July 2010

Persuadée que le rôle accru des musées dans la société américaine contemporaine l'obligeait à réexaminer leurs responsabilités, l'Association américaine des musées a entrepris de réviser sa déclaration de 1978 sur la déontologie professionnelle. Ce processus, qui a déclenché un débat national sur toute une série de questions épineuses, a conduit à l'adoption d'un certain nombre de directives recommandant aux musées d'outrepasser les normes purement juridiques, de prendre des mesures pour préserver l'intégrité de leurs finds et mériter la confiance du public. Ancien président de l'Association américaine des musées, l'auteur est actuellement directeur du Musée de la ville de New York.
Le restaurateur: polyvalence et adaptabilité
Authors: Barclay R. J.
Published: July 2010

«Quelle est aujourd'hui la tâche d'un restaurateur?», se demande R. J. Barclay, restaurateur en chef à la section d'ethnologie de l'Institut canadien de la conservation. Sa réponse prend en compte l'évolution d'une profession essentiellement technique, qui peu à peu en est venue à jouer un rôle central dans une muséologie de plus en plus marquée par l'interdisciplinarité.
Bibliothécaire de musée: un metier de partenariat
Authors: Elgaard Berit
Published: July 2010

La bibliothèque d'un musée nest pas une bibliothèque comme les autres. C'est ce quexplique Berit Elgaard, secrétaire du Comité international pour la documentation (CIDOC) du Conseil international des musées (ICOM).
L‘Égypte ancienne en Russie, en Ukraine, dans le Caucase, dans les pays baltes et en Asie centrale
Authors: Hodjash Svetlana
Published: July 2010

Outre les grandes collections d'antiquités égyptiennes de Moscou et de Saint‐Pétersbourg, plusieurs musées des territoires de l'ex‐Union soviétique abritent des objets importants, généralement peu connus. L'article de Svetlana Hodjash explique comment ces objets ont pour la première fois été réunis. L'auteur est la directrice du Département des antiquités orientales du musée d'État A. S. Pouchkine, à Moscou. Elle compte à son actif 160 publications sur l'art et la culture de l'Égypte, du Proche‐Orient et du royaume d'Ourartou, en Arménie (VIIIe siècle avant l'ère chrétienne), dont elle est une spécialiste reconnue pour avoir dirigé pendant vingt ans les fouilles archéologiques.
Inventorier la biodiversité: un point de vue africain
Authors: Komen Joris
Published: July 2010

Bien qu'une sensibilisation accrue à la conservation de la biodiversité ait mis en lumiere le rôle capital joué par les collections biologiques des musées, il semble que l'on n'ait guère pris conscience de l'impérieuse nécessité d'en dresser des inventaires. Joris Komen estime que les musées devraient s'employer en priorité à rendre leurs collections accessibles et utiles à la communauté Internationale. L'auteur est conservateur de la section des oiseaux au National Museum de Namibie. Il a étudié pendant de nombreuses années l'avifaune endémique de la zone aride de l'Afrique du Sud‐Ouest, centrant ses recherches sur la comparaison des caractères comportementaux on vocaux et des systémes d'accouplement, ainsi que sur d'autres méthodes << non traditionnelles >> de systématique biologique.
Océanopolis: la vitrine d'une recherche
Authors: de Beaulieu François , Quéméner Hervé
Published: July 2010

La région brestoise concentre aujourd'hui 50% de la recherche océanographique française. Océanopolis est à la fois la vitrine de cette recherche destinée au grand public et un acteur à part entière pour tout ce qui concerne les mammifères marins. Si tons les partenaires engagés dans le projet nourrissaient de grands espoirs, aucun n'aurait osé prévoir un succès si exceptionnel. L'écrivain François de Beaulieu et le journaliste Hervé Quéméner relatent ce phénomène.
Vitamin D deficiency: the time to ignore it has passed
Authors: HAROON Muhammad , REGAN Michael J.
Published: July 2010

It is true to say that it is just over the past decade and even more so in this new decade that it has become appreciated how vitally important vitamin D is for optimum health. This ‘sunshine’ vitamin could justifiably be called ‘the nutrient of this decade’. Until recently, vitamin D was known primarily for its role in bone health. However, as a result of advances in research this perspective has changed. While it is true to say that the classic function of vitamin D is to control calcium and vitamin D metabolism, we now know that the importance of vitamin D spreads far wider than just bone health. There is much ongoing research with regard to its emerging role in immunopathology, as a potent inhibitor of cellular growth, stimulator of insulin secretion, modulator of immune function and inhibitor of renin production. This review discusses the current evidence with regard to the clinical consequences of vitamin D deficiency and underscores the fact that physicians should be vigilant in searching for and treating this preventable and treatable condition. Furthermore, this review highlights the fact that the time is opportune for rheumatologists to agree upon clinical guidelines to advise practitioners as to when and in which patients to check for, what target vitamin D level to aim for and how best to treat vitamin D deficiency.
A COMPARISON OF ORDER‐RELEASE AND DISPATCH RULES FOR THE DYNAMIC WEIGHTED EARLY/TARDY PROBLEM
Authors: ROHLEDER THOMAS R. , SCUDDER GARY
Published: July 2010

The early/tardy problem is one of the most vexing pieces of the complex production scheduling decision process. So far most of the research has been on single‐machine environments. Hence, we considered the weighted early/tardy scheduling problem in a simulated dynamic multimachine job shop. We analyzed controlled job‐release and dispatch rules using time and cost information at a variety of stationary and nonstationary utilization rates, due‐date allowances, and early/tardy cost levels.

We found a newly developed method for controlling the release for all job operations using early/tardy cost information, superior to other release mechanisms overall in both our stationary and nonstationary analyses. We found immediate release useful at many high utilization conditions and a gateway‐only release method best in many low utilization conditions. A modified version of a single‐machine early/tardy dispatch method was clearly superior to the dispatch rules for almost all the simulated shop conditions.
LOGISTICS PARTNERSHIPS AND SUPPLY CHAIN RESTRUCTURING: SURVEY RESULTS FROM THE U.S. COMPUTER INDUSTRY
Authors: KOPCZAK LAURA ROCK
Published: July 2010

This research investigates the interaction between formation of logistics partnerships and supply chain restructuring in the U.S. computer industry via a survey of 30 ongoing partnerships. Partnerships that have included restructuring are compared to those that have not. Examples of representative partnerships are presented. The survey results indicate that restructurers use partnerships to facilitate restructuring. Restructurers and non‐restructurers form partnerships for different reasons and realize different types of benefits. Furthermore, restructurers realize greater benefits than do non‐restructurers and view their partnerships as more successful. Restructurers report dramatic improvements in logistics cost (1l‐30%) and order cycle time (62%). The research contributes to the existing literature by highlighting restructuring as an important aspect of logistics partnership formation and by presenting empirical data that shows how the two strategies are linked.
Coordinating Sales and Raw Material Discounts in a Global Supply Chain
Authors: Souza Gilvan C. , Zhao Zhenying , Chen Maomao , Ball And Michael O.
Published: July 2010

In this paper, the supplier of a key component to a global manufacturer offers a one‐time price discount; we study the firm's optimal response to the discount under two different strategies. In the first strategy, the firm does not pass along the discount to its customers (sales subsidiaries); the firm simply coordinates purchasing and production among the different factories to take advantage of this one‐time price discount. In the second strategy, the firm offers price discounts for its most profitable products in different sales subsidiaries to increase their demand. We carried out experiments for the two strategies based on a mathematical programming model, built around Toshiba's global notebook supply chain. Model constraints include, among others, material constraints, bill‐of‐materials, capacity and transportation constraints, minimum lot size constraints, and a constraint on minimum fill rate (service level constraint). Unlike most models of this type in the literature, which define variables in terms of single arc flows, we employ path variables, which allow for direct identification and manipulation of profitable and non‐profitable products.
Managing Disruption Risks in Supply Chains
Authors: Kleindorfer Paul R. , Saad Germaine H.
Published: July 2010

There are two broad categories of risk affecting supply chain design and management: (1) risks arising from the problems of coordinating supply and demand, and (2) risks arising from disruptions to normal activities. This paper is concerned with the second category of risks, which may arise from natural disasters, from strikes and economic disruptions, and from acts of purposeful agents, including terrorists. The paper provides a conceptual framework that reflects the joint activities of risk assessment and risk mitigation that are fundamental to disruption risk management in supply chains. We then consider empirical results from a rich data set covering the period 1995–2000 on accidents in the U. S. Chemical Industry. Based on these results and other literature, we discuss the implications for the design of management systems intended to cope with supply chain disruption risks.
An Empirical Model for Managing Quality in the Electronics Industry
Authors: Yeung Andy C. L. , Cheng T. C. Edwin , Lai Kee‐hung
Published: July 2010

Much of the empirical research in the past two decades has suggested that quality management (QM) is context dependent. This research develops an empirical QM model in a technology‐based sector—electronics manufacturing. Based on quantitative and qualitative investigations of 225 electronics firms in Hong Kong and the Pearl River Delta (PRD) region of China, a path analytic model is developed. The empirical model shows that a typical quality management system (QMS) in the electronics industry is composed of four major modules, namely leadership, cultural elements, operational support systems, and process management. These modules create a series of chain effects on organizational performance, rather than acting as parallel elements with an equal impact. By quantifying their effects on organizational performance and comparing the model to others in the literature, we identify those QM constructs that are context dependent. In electronics manufacturing, process management and customer focus are more important than other elements (e.g., cultural factors) for garnering business results. This study contributes to contingency theory and research by identifying the key constructs and their relationships in a competitive, volatile, and technology‐based industry with complex supply networks.
A Survey of Activity Network‐Based Process Models for Managing Product Development Projects
Authors: Browning Tyson R. , Ramasesh Ranga V.
Published: July 2010

Given the crucial role of process modeling in product development (PD) project management research and practice, and the variety of models proposed in the literature, a survey of the PD process modeling literature is timely and valuable. In this work, we focus on the activity network‐based process models that support PD project management and present a comprehensive survey of the literature published in the last decade. To organize our survey, we use a framework based on the purposes of PD process models: project visualization, project planning, project control, and project development. For each purpose, we provide an overview of the relevant models, highlight their key assumptions and findings, synthesize key insights, and illuminate avenues for further research. Although the survey reveals many insights and opportunities, five major areas for future study became apparent: activity interactions, global process improvements, process models as an organizing structure for knowledge management, modeling in cases of uncertainty and ambiguity, and determining the optimum amount of process prescription and structure for an innovative project.
The Modern Call Center: A Multi‐Disciplinary Perspective on Operations Management Research
Authors: Aksin Zeynep , Armony Mor , Mehrotra Vijay
Published: July 2010

Call centers are an increasingly important part of today's business world, employing millions of agents across the globe and serving as a primary customer‐facing channel for firms in many different industries. Call centers have been a fertile area for operations management researchers in several domains, including forecasting, capacity planning, queueing, and personnel scheduling. In addition, as telecommunications and information technology have advanced over the past several years, the operational challenges faced by call center managers have become more complicated. Issues associated with human resources management, sales, and marketing have also become increasingly relevant to call center operations and associated academic research.

In this paper, we provide a survey of the recent literature on call center operations management. Along with traditional research areas, we pay special attention to new management challenges that have been caused by emerging technologies, to behavioral issues associated with both call center agents and customers, and to the interface between call center operations and sales and marketing. We identify a handful of broad themes for future investigation while also pointing out several very specific research opportunities.
Genetic Factors Associated with Elevated Carbapenem Resistance in KPC-Producing
Klebsiella pneumoniae
Authors: Kitchel Brandon , Rasheed J. Kamile , Endimiani Andrea , Hujer Andrea M. , Anderson Karen F. , Bonomo Robert A. , Patel Jean B.
Published: July 2010

In the United States, the most prevalent mechanism of carbapenem resistance among
Enterobacteriaceae
is the production of a
Klebsiella pneumoniae
carbapenemase (KPC). KPC-producing isolates often exhibit a range of carbapenem MICs. To better understand the factors that contribute to overall carbapenem resistance, we analyzed 27 KPC-producing
K. pneumoniae
isolates with different levels of carbapenem resistance, 11 with low-level (i.e., meropenem or imipenem MIC ≤ 4 μg/ml), 2 with intermediate-level (i.e., meropenem and imipenem MIC = 8 μg/ml), and 14 with high-level (i.e., imipenem or meropenem MIC ≥ 16 μg/ml) carbapenem resistance, that were received from throughout the United States. Among 14 isolates that exhibited high-level carbapenem resistance, Western blot analysis indicated that 10 produced an elevated amount of KPC. These isolates either contained an increased
bla
KPC
gene copy number (
n
= 3) or had deletions directly upstream of the
bla
KPC
gene (
n
= 7). Four additional isolates lacked elevated KPC production but had high-level carbapenem resistance. Porin sequencing analysis identified 22 isolates potentially lacking a functional OmpK35 and three isolates potentially lacking a functional OmpK36. The highest carbapenem MICs were found in two isolates that lacked both functioning porins and produced elevated amounts of KPC. The 11 isolates with low-level carbapenem resistance contained neither an upstream deletion nor increased
bla
KPC
copy number. These results suggest that both
bla
KPC
copy number and deletions in the upstream genetic environment affect the level of KPC production and may contribute to high-level carbapenem resistance in KPC-producing
K. pneumoniae
, particularly when coupled with OmpK36 porin loss.
Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
Authors: Jacobson Jeffrey M. , Lalezari Jacob P. , Thompson Melanie A. , Fichtenbaum Carl J. , Saag Michael S. , Zingman Barry S. , D'Ambrosio Paul , Stambler Nancy , Rotshteyn Yakov , Marozsan Andre J. , Maddon Paul J. , Morris Stephen A. , Olson William C.
Published: July 2010

The anti-CCR5 antibody PRO 140 has shown potent and prolonged antiretroviral activity in subjects infected with CCR5-tropic (R5) HIV-1. Prior studies have examined single intravenous doses ranging up to 5 mg/kg of body weight or up to three subcutaneous doses ranging up to 324 mg. Here we report the results of a randomized, double-blind, placebo-controlled trial that examined the antiviral activity, tolerability, and pharmacokinetics of single 5-mg/kg and 10-mg/kg intravenous infusions of PRO 140 in 31 treated subjects. Eligibility criteria included HIV-1 RNA levels of >5,000 copies/ml, CD4+cell counts of >300/μl, no antiretroviral therapy for ≥12 weeks, and detection of only R5 HIV-1 in the original Trofile assay. Following poststudy testing with an enhanced-sensitivity Trofile assay, one subject treated with 10 mg/kg was reclassified as having dual/mixed-tropic virus at screening, and the data for that subject were censored from efficacy analyses. The mean maximum reduction of the HIV-1 RNA level from the baseline level was 1.8 log10units for both the 5-mg/kg and 10-mg/kg doses (P< 0.0001 relative to placebo). Viral loads reached their nadir at day 12 posttreatment and remained significantly (P< 0.01) reduced through day 29 for both PRO 140 dose groups. Treatment was generally well tolerated, with no dose-limiting toxicity being observed. Peak serum concentrations and overall exposures increased proportionally with dose. In summary, single 5-mg/kg and 10-mg/kg doses of PRO 140 exhibited potent, long-lived antiviral activity and were generally well tolerated. The findings further delineate the safety and antiviral properties of this novel, long-acting antiretroviral agent.
Dissemination of an
Enterococcus
Inc18-Like
vanA
Plasmid Associated with Vancomycin-Resistant
Staphylococcus aureus
Authors: Zhu Wenming , Murray Patrick R. , Huskins W. Charles , Jernigan John A. , McDonald Lawrence C. , Clark Nancye C. , Anderson Karen F. , McDougal Linda K. , Hageman Jeff C. , Olsen-Rasmussen Melissa , Frace Mike , Alangaden George J. , Chenoweth Carol , Zervos Marcus J. , Robinson-Dunn Barbara , Schreckenberger Paul C. , Reller L. Barth , Rudrik James T. , Patel Jean B.
Published: July 2010

Of the 9 vancomycin-resistant
Staphylococcus aureus
(VRSA) cases reported to date in the literature, 7 occurred in Michigan. In 5 of the 7 Michigan VRSA cases, an Inc18-like
vanA
plasmid was identified in the VRSA isolate and/or an associated vancomycin-resistant
Enterococcus
(VRE) isolate from the same patient. This plasmid may play a critical role in the emergence of VRSA. We studied the geographical distribution of the plasmid by testing 1,641 VRE isolates from three separate collections by PCR for plasmid-specific genes
traA
,
repR
, and
vanA
. Isolates from one collection (phase 2) were recovered from surveillance cultures collected in 17 hospitals in 13 states. All VRE isolates from 2 Michigan institutions (
n
= 386) and between 60 and 70 VRE isolates (
n
= 883) from the other hospitals were tested. Fifteen VRE isolates (3.9%) from Michigan were positive for an Inc18-like
vanA
plasmid (9
E. faecalis
[12.5%], 3
E. faecium
[1.0%], 2
E. avium
, and 1
E. raffinosus
). Six VRE isolates (0.6%) from outside Michigan were positive (3
E. faecalis
[2.7%] and 3
E. faecium
[0.4%]). Of all
E. faecalis
isolates tested, 6.0% were positive for the plasmid, compared to 0.6% for
E. faecium
and 3.0% for other spp. Fourteen of the 15 plasmid-positive isolates from Michigan had the same Tn
1546
insertion site location as the VRSA-associated Inc18-like plasmid, whereas 5 of 6 plasmid-positive isolates from outside Michigan differed in this characteristic. Most plasmid-positive
E. faecalis
isolates demonstrated diverse patterns by PFGE, with the exception of three pairs with indistinguishable patterns, suggesting that the plasmid is mobile in nature. Although VRE isolates with the VRSA-associated Inc18-like
vanA
plasmid were more common in Michigan, they remain rare. Periodic surveillance of VRE isolates for the plasmid may be useful in predicting the occurrence of VRSA.
In Vitro
Pharmacokinetic and Pharmacodynamic Evaluation of S-013420 against
Haemophilus influenzae
and
Streptococcus pneumoniae
Authors: Homma Tomoyuki , Hori Toshihiko , Ohshiro Merime , Maki Hideki , Yamano Yoshinori , Shimada Jingoro , Kuwahara Shogo
Published: July 2010

The pharmacokinetic (PK)/pharmacodynamic (PD) parameters and the antibacterial activity of S-013420, a novel bicyclolide, against
Haemophilus influenzae
and
Streptococcus pneumoniae
, including macrolide-resistant isolates, were investigated using an
in vitro
PD model. Various time-concentration curves were artificially constructed by modifying the PK data obtained in phase I studies. The activity against
H. influenzae
was evaluated using two parameters, that is, the area above the killing curve (AAC) and the viable cell reduction at 24 h. The relationships between the antibacterial activity of S-013420 and the three PK/PD parameters were investigated by fitting the data to the sigmoid maximum effective concentration model. The square of the correlation coefficient (
R
2
) values for AAC versus the area under the concentration-time curve from 0 to 24 h (AUC
0-24
)/MIC, the peak concentration (
C
max
)/MIC, and the cumulative percentage of a 24-h period that the drug concentration exceeded the MIC under steady-state PK conditions (%
T
MIC
) were 0.92, 0.87, and 0.49, respectively. The
R
2
values for viable cell reduction at 24 h versus AUC
0-24
/MIC,
C
max
/MIC, and %
T
MIC
were 0.93, 0.61, and 0.56, respectively. These results demonstrated that AUC
0-24
/MIC is the most significant parameter for evaluation of the antibacterial activity of S-013420. The values of AUC
0-24
/MIC required for maximum and static efficacy were 10.8 and 9.63, respectively, for
H. influenzae
and 16.3 to 22.3 and 4.66 to 9.01, respectively, for
S. pneumoniae
. This analysis is considered useful for determining the AUC value at the infection site, which would be required for efficacy in clinical use.
Role of Arginine Deiminase of
Streptococcus cristatus
in
Porphyromonas gingivalis
Colonization
Authors: Wu Jie , Xie Hua
Published: July 2010

The ability to attach to a variety of oral surfaces is an important characteristic of
Porphyromonas gingivalis
. Previous studies have demonstrated that expression and production of FimA, a major subunit protein of the long fimbriae, is required for
P. gingivalis
colonization. Here we report that a surface protein, arginine deiminase (ArcA) of
Streptococcus cristatus
, represses FimA production and inhibits biofilm formation of
P. gingivalis
. This inhibitory function of ArcA is also observed in the formation of heterotypic
P. gingivalis-Streptococcus gordonii
biofilms.
P. gingivalis
is released from streptococcal substrates in the presence of ArcA, likely due to an inhibition of FimA production. This work suggests that ArcA may have the potential to be a specific antibiofilm agent to fight
P. gingivalis
infections.
Efficacy and Safety of Nemonoxacin versus Levofloxacin for Community-Acquired Pneumonia
Authors: van Rensburg Dirkie J. J. , Perng Reury-Perng , Mitha Ismail H. , Bester Andrè J. , Kasumba Joseph , Wu Ren-Guang , Ho Ming-Lin , Chang Li-Wen , Chung David T. , Chang Yu-Ting , King Chi-Hsin R. , Hsu Ming-Chu
Published: July 2010

Nemonoxacin, a novel nonfluorinated quinolone, exhibits potent
in vitro
and
in vivo
activities against community-acquired pneumonia (CAP) pathogens, including multidrug-resistant
Streptococcus pneumoniae
. Patients with mild to moderate CAP (
n
= 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. Clinical responses were determined at the test-of-cure visit in intent-to-treat (ITT), clinical per protocol (PPc), evaluable-ITT, and evaluable-PPc populations. The clinical cure rates for 750 mg nemonoxacin, 500 mg nemonoxacin, and levofloxacin were 89.9%, 87.0%, and 91.1%, respectively, in the evaluable-ITT population; 91.7%, 87.7%, and 90.3%, respectively, in the evaluable-PPc population; 82.6%, 75.3%, and 80.0%, respectively, in the ITT population; and 83.5%, 78.0%, and 82.3%, respectively, in the PPc population. Noninferiority to levofloxacin was demonstrated in both the 750-mg and 500-mg nemonoxacin groups for the evaluable-ITT and evaluable-PPc populations, and also in the 750 mg nemonoxacin group for the ITT and PPc populations. Overall bacteriological success rates were high for all treatment groups in the evaluable-bacteriological ITT population (90.2% in the 750 mg nemonoxacin group, 84.8% in the 500 mg nemonoxacin group, and 92.0% in the levofloxacin group). All three treatments were well tolerated, and no drug-related serious adverse events were observed. Overall, oral nemonoxacin (both 750 mg and 500 mg) administered for 7 days resulted in high clinical and bacteriological success rates in CAP patients. Further, good tolerability and excellent activity against common causative pathogens were demonstrated. Nemonoxacin (750 mg and 500 mg) once daily is as effective and safe as levofloxacin (500 mg) once daily for the treatment of CAP.
Clinical Evaluation of a Dried Blood Spot Assay for Atazanavir
Authors: Van Schooneveld Trevor , Swindells Susan , Nelson Sarah R. , Robbins Brian L. , Moore Ryan , Fletcher Courtney V.
Published: July 2010

Current procedures for obtaining and measuring plasma concentrations of HIV protease inhibitors (PIs) are technically challenging. Dried blood spot (DBS) assays offer a way to overcome many of the obstacles. We sought to develop a DBS assay for quantitation of the PI atazanavir (ATV) and to compare this method with a previously validated plasma assay. We prospectively enrolled 48 patients with well-controlled HIV disease who had been on ATV for at least 7 days. ATV was quantified from plasma by use of high-performance liquid chromatography (HPLC). A reversed-phase ultrahigh-performance liquid chromatography (UPLC) assay was utilized for DBS samples. The concentrations of ATV quantified in a DBS matrix showed very strong agreement with those measured in plasma (
r
2
= 0.988). The mean difference in ATV concentration between the two methods was −10.8% (95% confidence interval [95% CI], −7.65% to −13.95%), indicating that the DBS method has a slight negative bias. A majority (97.8%) of the differences in concentration between the two assays fell within ±2 standard deviations. ATV concentrations were lower in subjects who had detectable HIV RNA in plasma (mean, 543 ng/ml) than in those with HIV RNA of <50 copies/ml (mean, 1,582 ng/ml) (
P
= 0.03, Wilcoxon rank-sum test). In conclusion, our study demonstrated that ATV quantitation in a DBS matrix is feasible and accurate. DBS use offers a convenient alternative for measuring plasma concentrations of ATV and may have utility in monitoring of drug concentrations in clinical practice and in future studies.
In Vivo
Protection Provided by a Synthetic New Alpha-Galactosyl Ceramide Analog against Bacterial and Viral Infections in Murine Models
Authors: Lin Kun-Hsien , Liang Jian-Jong , Huang Wen-I , Lin-Chu Shao-Ying , Su Ching-Yao , Lee Yi-Ling , Jan Jia-Tsong , Lin Yi-Ling , Cheng Yih-Shyun E. , Wong Chi-Huey
Published: July 2010

Alpha-galactosyl ceramide (α-GalCer) has been known to bind to the CD1d receptor on dendritic cells and activate invariant natural killer T (iNKT) cells, which subsequently secrete T-helper-cell 1 (Th1) and Th2 cytokines, which correlate with anti-infection activity and the prevention of autoimmune diseases, respectively. α-GalCer elicits the secretion of these two cytokines nonselectively, and thus, its effectiveness is limited by the opposing effects of the Th1 and Th2 cytokines. Reported here is the synthesis of a new α-GalCer analog (compound C34), based on the structure of CD1d, with a 4-(4-fluorophenoxy) phenyl undecanoyl modification of the
N
-acyl moiety of α-GalCer. Using several murine bacterial and viral infection models, we demonstrated that C34 has superior antibacterial and antiviral activities in comparison with those of several other Th1-selective glycolipids and that it is most effective by administering it to mice in a prophylactic manner before or shortly after infection.
Pharmacokinetics, Safety, and Tolerability of Voriconazole in Immunocompromised Children
Authors: Walsh Thomas J. , Driscoll Timothy , Milligan Peter A. , Wood Nolan D. , Schlamm Haran , Groll Andreas H. , Jafri Hasan , Arrieta Antonio C. , Klein Nigel J. , Lutsar Irja
Published: July 2010

The pharmacokinetics of voriconazole in children receiving 4 mg/kg intravenously (i.v.) demonstrate substantially lower plasma exposures (as defined by area under the concentration-time curve [AUC]) than those in adults receiving the same therapeutic dosage. These differences in pharmacokinetics between children and adults limit accurate prediction of pediatric voriconazole exposure based on adult dosages. We therefore studied the pharmacokinetics and tolerability of higher dosages of an i.v.-to-oral regimen of voriconazole in immunocompromised children aged 2 to <12 years in two dosage cohorts for the prevention of invasive fungal infections. The first cohort received 4 mg/kg i.v. every 12 h (q12h), then 6 mg/kg i.v. q12h, and then 4 mg/kg orally (p.o.) q12h; the second received 6 mg/kg i.v. q12h, then 8 mg/kg i.v. q12h, and then 6 mg/kg p.o. q12h. The mean values for the AUC over the dosing interval (AUCτ) for 4 mg/kg and 6 mg/kg i.v. in cohort 1 were 11,827 and 22,914 ng·h/ml, respectively, whereas the mean AUCτ values for 6 mg/kg and 8 mg/kg i.v. in cohort 2 were 17,249 and 29,776 ng·h/ml, respectively. High interpatient variability was observed. The bioavailability of the oral formulation in children was approximately 65%. The safety profiles were similar in the two cohorts and age groups. The most common treatment-related adverse event was increased gamma glutamyl transpeptidase levels. There was no correlation between adverse events and voriconazole exposure. In summary, voriconazole was tolerated to a similar degree regardless of dosage and age; the mean plasma AUCτ for 8 mg/kg i.v. in children approached that for 4 mg/kg i.v. in adults, thus representing a rationally selected dosage for the pediatric population.
γδ T Cells but Not NK Cells Are Essential for Cell-Mediated Immunity againstPlasmodium chabaudiMalaria
Authors: Weidanz William P. , LaFleur GayeLyn , Brown Andrew , Burns James M. , Gramaglia Irene , van der Heyde Henri C.
Published: July 2010

Blood-stagePlasmodium chabaudiinfections are suppressed by antibody-mediated immunity and/or cell-mediated immunity (CMI). To determine the contributions of NK cells and γδ T cells to protective immunity, C57BL/6 (wild-type [WT]) mice and B-cell-deficient (JH−/−) mice were infected withP. chabaudiand depleted of NK cells or γδ T cells with monoclonal antibody. The time courses of parasitemia in NK-cell-depleted WT mice and JH−/−mice were similar to those of control mice, indicating that deficiencies in NK cells, NKT cells, or CD8+T cells had little effect on parasitemia. In contrast, high levels of noncuring parasitemia occurred in JH−/−mice depleted of γδ T cells. Depletion of γδ T cells during chronic parasitemia in B-cell-deficient JH−/−mice resulted in an immediate and marked exacerbation of parasitemia, suggesting that γδ T cells have a direct killing effectin vivoon blood-stage parasites. Cytokine analyses revealed that levels of interleukin-10, gamma interferon (IFN-γ), and macrophage chemoattractant protein 1 (MCP-1) in the sera of γδ T-cell-depleted mice were significantly (P< 0.05) decreased compared to hamster immunoglobulin-injected controls, but these cytokine levels were similar in NK-cell-depleted mice and their controls. The time courses of parasitemia in CCR2−/−and JH−/−× CCR2−/−mice and in their controls were nearly identical, indicating that MCP-1 is not required for the control of parasitemia. Collectively, these data indicate that the suppression of acuteP. chabaudiinfection by CMI is γδ T cell dependent, is independent of NK cells, and may be attributed to the deficient IFN-γ response seen early in γδ T-cell-depleted mice.
One step forward, two steps back? The GMC, the common law and ‘informed’ consent
Authors: Fovargue Sara , Miola José
Published: July 2010

Until 2008, if doctors followed the General Medical Council's (GMC's) guidance on providing information prior to obtaining a patient's consent to treatment, they would be going beyond what was technically required by the law. It was hoped that the common law would catch up with this guidance and encourage respect for patients' autonomy by facilitating informed decision-making. Regrettably, this has not occurred. For once, the law's inability to keep up with changing medical practice and standards is not the problem. The authors argue that while the common law has moved forward and started to recognise the importance of patient autonomy and informed decision-making, the GMC has taken a step back in their 2008 guidance on consent. Indeed, doctors are now required to tell their patients less than they were in 1998 when the last guidance was produced. This is an unfortunate development and the authors urge the GMC to revisit their guidance.
The awareness and use of chaperones by patients in an English general practice
Authors: Pydah K L , Howard J
Published: July 2010

Objective

To ascertain and improve the understanding and use of chaperones among the patients of an English general practice (GP).

Background

Doctors have long been advised to have a third party present during intimate physical examinations. Little is known about the understanding of the term in the general population in England and the consequences of this for the promotion and use of chaperones in GP. We audited the understanding and use of chaperones in an English GP. The aim of the study was to increase the awareness of the availability of chaperones in our population.

Methods

A questionnaire was given randomly to 100 patients attending the GP surgery. Participants were asked about their awareness of and frequency of requesting a chaperone while undergoing intimate examinations. Based on the initial results, a poster was designed for the waiting room to increase awareness. Data were collected with the same questionnaire to see if the new poster altered surgery attendees understanding and likely subsequent use of chaperones.

Results

In the initial audit, 29% of patients were unaware of the termchaperone, and only one person (1%) had ever requested a chaperone. After the introduction of a specially designed poster, the results showed an improvement in awareness from 71% to 89%, and the likely frequency of using a chaperone increased from 1% to 4%.

Conclusion

There is a need to improve the understanding of the general population about chaperones if we are to see greater use of chaperones in GP.
Software development with code maps
Authors: DeLine Robert , Venolia Gina , Rowan Kael
Published: July 2010

Could ubiquitous hand-drawn code map diagrams become a thing of the past?
Puzzled: Figures on a plane
Authors: Winkler Peter
Published: July 2010

Welcome to three new puzzles. Solutions to the first two will be published next month; the third is (as yet) unsolved. In each, the issue is how your intuition matches up with the mathematics.
Celebrating the legacy of PLATO
Authors: Kroeker Kirk L.
Published: July 2010

The PLATO@50 Conference marked the semicentennial of the computer system that was the forerunner of today's social media and interactive education.
A Survey on Uncertainty Management in Data Integration
Authors: Magnani Matteo , Montesi Danilo
Published: July 2010

In the last few years, uncertainty management has come to be recognized as a fundamental aspect of data integration. It is now accepted that it may not be possible to remove uncertainty generated during data integration processes and that uncertainty in itself may represent a source of relevant information. Several issues, such as the aggregation of uncertain mappings and the querying of uncertain mediated schemata, have been addressed by applying well-known uncertainty management theories. However, several problems lie unresolved. This article sketches an initial picture of this highly active research area; it details existing works in the light of a homogeneous framework, and identifies and discusses the leading issues awaiting solutions.
Extract and infer quickly
Authors: Gim Jongmin , Won Youjip
Published: July 2010

The modern hard disk drive is a complex and complicated device. It consists of 2--4 heads, thousands of sectors per track, several hundred thousands of tracks, and tens of zones. The beginnings of adjacent tracks are placed with a certain angular offset. Sectors are placed on the tracks and accessed in some order. Angular offset and sector placement order vary widely subject to vendors and models. The success of an efficient file and storage subsystem design relies on the proper understanding of the underlying storage device characteristics. The characterization of hard disk drives has been a subject of intense research for more than a decade. The scale and complexity of state-of-the-art hard disk drive technology calls for a new way of extracting and analyzing the characteristics of the hard disk drive. In this work, we develop a novel disk characterization suite, DIG (Disk Geometry Analyzer), which allows us to rapidly extract and characterize the key performance metrics of the modern hard disk drive. Development of this tool is accompanied by thorough examination of four off-the-shelf hard disk drives. DIG consists of three key ingredients:
O
(1) a track boundary detection algorithm;
O
(log
n
) a zone boundary detection algorithm; and hybrid sampling based seek time profiling. We particularly focus on addressing the scalability aspect of disk characterization. With DIG, we are able to extract key metrics of hard disk drives, for example, track sizes, zone information, sector geometry and so on, within 3--20 minutes. DIG allows us to determine the sector layout mechanism of the underlying hard disk drive, for example, hybrid serpentine, cylinder serpentine, and surface serpentine, and to a build complete sector map from LBN to the three dimensional space of (Cylinder, Head, Sector). Examining the hard disk drives with DIG, we made a number of important observations. In modern hard disk drives, head switch overhead is far greater than track switch overhead. It seems that hard disk drive vendors put greater emphasis on reducing the number of head switches for data access. Most disk vendors use surface serpentine, cylinder serpentine, or hybrid serpentine schemes in laying sectors on the platters. The legacy seek time model, which takes the form of
a
+
b
√
d
leaves much to be desired for use in modern hard disk drives especially for short seeks (less than 5000 tracks). We compare the performance of the DIG against the existing state-of-the-art disk profiling algorithm. Compared to the existing state-of-the-art disk characterization algorithm, the DIG algorithm significantly decreases the time to extract comprehensive sector geometry information from 1920 minutes to 7 minutes and 1927 minutes to 180 minutes in best and worst case scenarios, respectively.