bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of
Streptococcus pneumoniae
Biofilm Mutants and Their Characterization during Nasopharyngeal Colonization
Authors: Muñoz-Elías Ernesto J. , Marcano Joan , Camilli Andrew
Published: September 2008

Asymptomatic colonization of the nasopharynx by
Streptococcus pneumoniae
precedes pneumococcal disease, yet pneumococcal colonization factors remain poorly understood. Many bacterial infections involve biofilms which protect bacteria from host defenses and antibiotics. To gain insight into the genetics of biofilm formation by
S. pneumoniae
, we conducted an in vitro screen for biofilm-altered mutants with the serotype 4 clinical isolate TIGR4. In a first screen of 6,000
mariner
transposon mutants, we repeatedly isolated biofilm-overproducing acapsular mutants, suggesting that the capsule was antagonistic to biofilm formation. Therefore, we screened 6,500 additional transposon mutants in an
S. pneumoniae
acapsular background. Following this approach, we isolated 69 insertions in 49 different genes. The collection of mutants includes genes encoding bona fide and putative choline binding proteins, adhesins, synthases of membrane and cell wall components, extracellular and cell wall proteases, efflux pumps, ABC and PTS transporters, and transcriptional regulators, as well as several conserved and novel hypothetical proteins. Interestingly, while four insertions mapped to
rrgA
, encoding a subunit of a recently described surface pilus,
rrgB
and
rrgC
(encoding the other two pilus subunits) mutants had no biofilm defects, implicating the RrgA adhesin but not the pilus structure per se in biofilm formation. To correlate our findings to the process of colonization, we transferred a set of 29 mutations into the wild-type encapsulated strain and then tested the fitness of the mutants in vivo. Strikingly, we found that 23 of these mutants were impaired for nasopharyngeal colonization, thus establishing a link between biofilm formation and colonization.
Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice
Authors: Londoño Diana , Marques Adriana , Hornung Ronald L. , Cadavid Diego
Published: September 2008

Relapsing fever (RF) is a spirochetal infection characterized by periods of sickness with fever at time of high bacteremia that alternate with afebrile periods of relative well being during low bacteremia. Patients with epidemic RF who are doing relatively well have extraordinarily high levels of interleukin-10 (IL-10) in the circulation. We investigated the possibility that IL-10 plays an important protective role in this infection using wild-type and IL-10-deficient mice inoculated with virulent serotype 2 of the RF spirocheteBorrelia turicatae. During peak bacteremia there was increased systemic production of IL-10 that quickly resolved in the postpeak period; in contrast, IL-6 and CXCL13 production increased during the peak but remained elevated during postpeak bacteremia. IL-10 deficiency resulted in lower bacteremia, increased specific antibody production, higher production of CXCL13 and IL-6, and thrombotic and hemorrhagic complications affecting multiple organs with secondary tissue injury. Our results revealed that production of IL-10 is highly regulated during RF and plays an important protective role in the prevention of hemorrhagic and thrombotic complications at the cost of reduced pathogen control.
Analysis of the Genotype and Virulence of
Staphylococcus epidermidis
Isolates from Patients with Infective Endocarditis
Authors: Monk Alastair B. , Boundy Sam , Chu Vivian H. , Bettinger Jill C. , Robles Jaime R. , Fowler Vance G. , Archer Gordon L.
Published: September 2008

Staphylococcus epidermidis
is one of the most common causes of infections of prosthetic heart valves (prosthetic valve endocarditis [PVE]) and an increasingly common cause of infections of native heart valves (native valve endocarditis [NVE]). While
S. epidermidis
typically causes indolent infections of prosthetic devices, including prosthetic valves and intravascular catheters,
S. epidermidis
NVE is a virulent infection associated with valve destruction and high mortality. In order to see if the differences in the course of infection were due to characteristics of the infecting organisms, we examined 31
S. epidermidis
NVE and 65 PVE isolates, as well as 21 isolates from blood cultures (representing bloodstream infections [BSI]) and 28 isolates from nasal specimens or cultures considered to indicate skin carriage. Multilocus sequence typing showed both NVE and PVE isolates to have more unique sequence types (types not shared by the other groups; 74 and 71%, respectively) than either BSI isolates (10%) or skin isolates (42%). Thirty NVE, 16 PVE, and a total of 9 of the nasal, skin, and BSI isolates were tested for virulence in
Caenorhabditis elegans
. Twenty-one (70%) of the 30 NVE isolates killed at least 50% of the worms by day 5, compared to 1 (6%) of 16 PVE isolates and 1 (11%) of 9 nasal, skin, or BSI isolates. In addition, the
C. elegans
survival rate as assessed by log rank analyses of Kaplan-Meier survival curves was significantly lower for NVE isolates than for each other group of isolates (
P
< 0.0001). There was no correlation between the production of poly-β(1-6)-
N
-acetylglucosamine exopolysaccharide and virulence in worms. This study is the first analysis suggesting that
S. epidermidis
isolates from patients with NVE constitute a more virulent subset within this species.
Contribution of the Ler- and H-NS-Regulated Long Polar Fimbriae of
Escherichia coli
O157:H7 during Binding to Tissue-Cultured Cells
Authors: Torres Alfredo G. , Slater Terry M. , Patel Shilpa D. , Popov Vsevolod L. , Arenas-Hernández Margarita M. P.
Published: September 2008

The expression of the long polar fimbriae (LPF) of enterohemorrhagic
Escherichia coli
(EHEC) O157:H7 is controlled by a tightly regulated process, and, therefore, the role of these fimbriae during binding to epithelial cells has been difficult to establish. We recently found that histone-like nucleoid-structuring protein (H-NS) binds to the regulatory sequence of the
E. coli
O157:H7
lpf1
operon and “silences” its transcription, while Ler inhibits the action of the H-NS protein and allows
lpf1
to be expressed. In the present study, we determined how the deregulated expression of LPF affects binding of EHEC O157:H7 to tissue-cultured cells, correlating the adherence phenotype with
lpf1
expression. We tested the adherence properties of EHEC
hns
mutant and found that this strain adhered 2.8-fold better than the wild type. In contrast, the EHEC
ler
mutant adhered 2.1-fold less than the wild type. The EHEC
hns ler
mutant constitutively expressed the
lpf
genes, and, therefore, we observed that the double mutant adhered 5.6-fold times better than the wild type. Disruption of
lpfA
in the EHEC
hns
and
hns ler
mutants or the addition of anti-LpfA serum caused a reduction in adhesion, demonstrating that the increased adherence was due to the expression of LPF. Immunogold-labeling electron microscopy showed that LPF is present on the surface of EHEC
lpfA
+
strains. Furthermore, we showed that EHEC expressing LPF agglutinates red blood cells from different species and that the agglutination was blocked by the addition of anti-LpfA serum. Overall, our data confirmed that expression of LPF is a tightly regulated process and, for the first time, demonstrated that these fimbriae are associated with adherence and hemagglutination phenotypes in EHEC O157:H7.
Identification of a Bile-Induced Exopolysaccharide Required forSalmonellaBiofilm Formation on Gallstone Surfaces
Authors: Crawford Robert W. , Gibson Deanna L. , Kay William W. , Gunn John S.
Published: September 2008

Salmonella entericaserovar Typhi can establish a chronic, asymptomatic infection of the human gallbladder, suggesting that this bacterium utilizes novel mechanisms to mediate enhanced colonization and persistence in a bile-rich environment. Gallstones are one of the most important risk factors for developing carriage, and we have previously demonstrated that salmonellae form biofilms on human gallstones in vitro. Thus, we hypothesize that bile-induced biofilms on gallstone surfaces promote gallbladder colonization and maintenance of the carrier state. A colanic acid/celluloseS. entericaserovar Typhimurium double mutant formed a mature biofilm on gallstones in a test tube assay and in a new, gallstone-independent assay using cholesterol-coated Eppendorf tubes. These data suggest the presence of an unidentified exopolysaccharide necessary for mature biofilm development and demonstrate specific binding affinity between salmonellae and cholesterol. Our experiments indicate that theSalmonellaO-antigen capsule (yihU-yshAandyihV-yihW) is a crucial determinant in gallstone and cholesterol biofilms but that expression of this exopolysaccharide is not necessary for binding to glass or plastic. Real-time PCR revealed that growth in bile resulted in upregulation of the O-antigen capsule-encoding operon in anagfD-independent manner. Thus, the O-antigen capsule genes are bile induced, and the capsule produced by the enzymes of this operon is specifically required for biofilm formation on cholesterol gallstones. These studies provide new therapeutic targets for preventing asymptomatic serovar Typhi gallbladder carriage.
Identification of
Salmonella enterica
Serovar Dublin-Specific Sequences by Subtractive Hybridization and Analysis of Their Role in Intestinal Colonization and Systemic Translocation in Cattle
Authors: Pullinger Gillian D. , Dziva Francis , Charleston Bryan , Wallis Timothy S. , Stevens Mark P.
Published: September 2008

Salmonella enterica
serovar Dublin is a host-restricted serovar associated with typhoidal disease in cattle. In contrast, the fowl-associated serovar
S. enterica
serovar Gallinarum is avirulent in calves, yet it invades ileal mucosa and induces enteritis at levels comparable to those induced by
S. enterica
serovar Dublin. Suppression subtractive hybridization was employed to identify
S. enterica
serovar Dublin strain SD3246 genes absent from
S. enterica
serovar Gallinarum strain SG9. Forty-one
S. enterica
serovar Dublin fragments were cloned and sequenced. Among these, 24 mobile-element-associated genes were identified, and 12 clones exhibited similarity with sequences of known or predicted function in other serovars. Three
S. enterica
serovar Dublin-specific regions were homologous to regions from the genome of
Enterobacter
sp. strain 638. Sequencing of fragments adjacent to these three sequences revealed the presence of a 21-kb genomic island, designated
S. enterica
serovar Dublin island 1 (SDI-1). PCR analysis and Southern blotting showed that SDI-1 is highly conserved within
S. enterica
serovar Dublin isolates but rarely found in other serovars. To probe the role of genes identified by subtractive hybridization in vivo, 24 signature-tagged
S. enterica
serovar Dublin SD3246 mutants lacking loci not present in
Salmonella
serovar Gallinarum SG9 were created and screened by oral challenge of cattle. Though attenuation of tagged SG9 and SD3246
Salmonella
pathogenicity island-1 (SPI-1) and SPI-2 mutant strains was detected, no obvious defects of these 24 mutants were detected. Subsequently, a ΔSDI-1 mutant was found to exhibit weak but significant attenuation compared with the parent strain in coinfection of calves. SDI-1 mutation did not impair invasion, intramacrophage survival, or virulence in mice, implying that SDI-1 does not influence fitness per se and may act in a host-specific manner.
Brain histology
Authors: Jeans A , Esiri M
Published: September 2008

In this article we summarise nervous system histology in health and disease and acquaint the reader with developments in the staining techniques that are in current use, particularly immunostains. Although clinicians do not need to know the details of stain appearances, some familiarity with these aspects of neuropathology is invaluable in interpreting the reports they receive from the laboratory, as well as reminding them of the amazing beauty of the central nervous system’s microscopic structure.
Weakness on the intensive care unit
Authors: Howard R S , Tan S V , Z’Graggen W J
Published: September 2008

Patients who are recovering from critical illness may be weak and difficult to wean from ventilatory support as a complication of their underlying disorder, intercurrent events or treatment given during prolonged intensive care. These patients are difficult to assess because of the severity of their weakness and any accompanying encephalopathy. It is essential to undertake a meticulous review, including assessment of any septic, hypoxic or metabolic derangements and a detailed look at the dosage and duration of medication including antibiotics, neuromuscular junction blocking agents and sedation. If a primary underlying neurological cause or an intercurrent event have been excluded, the likeliest cause of weakness is one of the neuromuscular complications of critical care such as: critical care polyneuropathy, an acute axonal neuropathy which develops in patients with preceding sepsis or multi-organ failure; the use of neuromuscular junction blocking agents or steroids; and critical illness myopathy, which is the most common cause of critical care related weakness.
AN IMPORTANCE-AWARE ARCHITECTURE FOR LARGE-SCALE GRID INFORMATION SERVICES
Authors: ZANIKOLAS SERAFEIM , SAKELLARIOU RIZOS
Published: September 2008

This paper is concerned with the scalability of large-scale grid monitoring and information services, which are mainly used for the discovery of resources of interest. Large-scale grid monitoring systems have to balance between three competing performance metrics: query response time, imposed network overhead, and information freshness. Improving one of the three metrics will affect another; any solution will be based on a trade-off. The paper is motivated by the observation that existing grid monitoring systems can only be manually configured for a trade-off among the three metrics, which applies equally to all monitored resources; this implies that all resources in a grid are considered to be of equal importance. Assuming that in a large-scale grid setting this is unlikely to hold, the paper proposes an importance-based monitoring architecture for large-scale grid information services, based on an adaptation of the web crawling paradigm. The main idea is that, since not all resources are of equal importance, one can vary the trade-off based on the relative importance of the monitored resources. The proposed architecture is described and evaluated based on large-scale deployments of a prototype implementation on PlanetLab.
THE RELAXED-RING: A FAULT-TOLERANT TOPOLOGY FOR STRUCTURED OVERLAY NETWORKS
Authors: MEJÍAS BORIS , VAN ROY PETER
Published: September 2008

Fault-tolerance and lookup consistency are considered crucial properties for building applications on top of structured overlay networks. Many of these networks use the ring topology for the organization or their peers. The network must handle multiple joins, leaves and failures of peers while keeping the connection between every pair of successor-predecessor correct. This property makes the maintenance of the ring very costly and temporarily impossible to achieve, requiring periodic stabilization for fixing the ring. We introduce the relaxed-ring topology that does not rely on a perfect successor-predecessor relationship and it does not need a any periodic maintenance. Leaves and failures are considered as the same type of event providing a fault-tolerant and self-organizing maintenance of the ring. Relaxed-ring's limitations with respect to failure handling are formally identified, providing strong guarantees to develop applications on top of the architecture. Besides permanent failures, the paper analyses temporary failures and false suspicions caused by broken links, which are often ignored.
EDGeS: THE COMMON BOUNDARY BETWEEN SERVICE AND DESKTOP GRIDS
Authors: BALATON ZOLTAN , FARKAS ZOLTAN , GOMBAS GABOR , KACSUK PETER , LOVAS ROBERTO , MAROSI ATTILA CSABA , EMMEN AD , TERSTYANSZKY GABOR , KISS TAMAS , KELLEY IAN , TAYLOR IAN , LODYGENSKY OLEG , CARDENAS-MONTES MIGUEL , FEDAK GILLES , ARAUJO FILIPE
Published: September 2008

Service grids and desktop grids are both promoted by their supportive communities as great solutions for solving the available compute power problem and helping to balance loads across network systems. Little work, however, has been undertaken to blend these two technologies together. In this paper we introduce a new EU project, that is building technological bridges to facilitate service and desktop grid interoperability. We provide a taxonomy and background into service grids, such as EGEE and desktop grids or volunteer computing platforms, such as BOINC and XtremWeb. We then describe our approach for identifying translation technologies between service and desktop grids. The individual themes discuss the actual bridging technologies employed and the distributed data issues surrounding deployment.
AN EFFICIENT METHOD FOR NEAR-OPTIMAL POLYGONAL APPROXIMATION BASED ON DIFFERENTIAL EVOLUTION
Authors: SARKAR BISWAJIT
Published: September 2008

Polygonal approximation of digitized curves is an important step in shape representation and analysis. One of the approaches to obtain a good polygonal approximation is that of formulating the approximation task as an optimization problem and then solving it using the available tools. Adopting this strategy, in this article, we present a differential evolution-based method for polygonal approximation. We show that our method not only yields near-optimal results, but also does so very efficiently. The proposed method is also a demonstration of the successful application of differential evolution for solving a combinatorial optimization problem.
Lossy Joint Source-Channel Coding Using Raptor Codes
Authors: Bursalioglu O. Y. , Fresia M. , Caire G. , Poor H. V.
Published: September 2008

The straightforward application of Shannon's separation principle may entail a significant suboptimality in practical systems with limited coding delay and complexity. This is particularly evident when the lossy source code is based on entropy-coded quantization. In fact, it is well known that entropy coding is not robust to residual channel errors. In this paper, a joint source-channel coding scheme is advocated that combines the advantages and simplicity of entropy-coded quantization with the robustness of linear codes. The idea is to combine entropy coding and channel coding into a single linear encoding stage. If the channel is symmetric, the scheme can asymptotically achieve the optimal rate-distortion limit. However, its advantages are more clearly evident under finite coding delay and complexity. The sequence of quantization indices is decomposed into bitplanes, and each bitplane is independently mapped onto a sequence of channel coded symbols. The coding rate of each bitplane is chosen according to the bitplane conditional entropy rate. The use of systematic raptor encoders is proposed, in order to obtain a continuum of coding rates with a single basic encoding algorithm. Simulations show that the proposed scheme can outperform the separated baseline scheme for finite coding length and comparable complexity and, as expected, it is much more robust to channel errors in the case of channel capacity mismatch.
Some Fixed Point Theorem for Mapping on Complete G-Metric Spaces
Authors: Mustafa Zead , Obiedat Hamed , Awawdeh Fadi
Published: September 2008

We prove some fixed point results for mapping satisfying sufficient conditions on complete "Equation missing"-metric space, also we showed that if the "Equation missing"-metric space "Equation missing" is symmetric, then the existence and uniqueness of these fixed point results follow from well-known theorems in usual metric space "Equation missing", where "Equation missing" is the usual metric space which defined from the "Equation missing"-metric space "Equation missing".
PPAR Gamma Activators: Off‐Target Against Glioma Cell Migration and Brain Invasion
Authors: Seufert Sebastian , Coras Roland , Tränkle Christian , Zlotos Darius P. , Blümcke Ingmar , Tatenhorst Lars , Heneka Michael T. , Hahnen Eric
Published: September 2008

Today, there is increasing evidence that PPARγ agonists, including thiazolidinediones (TDZs) and nonthiazolidinediones, block the motility and invasiveness of glioma cells and other highly migratory tumor entities. However, the mechanism(s) by which PPARγ activators mediate their antimigratory and anti‐invasive properties remains elusive. This letter gives a short review on the debate and adds to the current knowledge by applying a PPARγ inactive derivative of the TDZ troglitazone (Rezulin) which potently counteracts experimental glioma progression in a PPARγ independent manner.
Guaranteed Performance Robust Kalman Filter for Continuous‐Time Markovian Jump Nonlinear System with Uncertain Noise
Authors: Zhu Jin , Park Junhong , Lee Kwan-Soo , Spiryagin Maksym
Published: September 2008

Robust Kalman filtering design for continuous‐time Markovian jump nonlinear systems with uncertain
noise was investigated. Because of complexity of Markovian jump systems, the statistical characteristics of system noise and observation noise are time‐varying or unmeasurable instead of being stationary. In view of robust estimation, maximum admissible upper bound of the uncertainty to noise covariance matrix was given based on system state estimation performance. As long as the noise uncertainty is limited within this bound via noise control, the Kalman filter has robustness against noise uncertainty, and stability of dynamic systems can be
ensured. It is proved by game theory that this design is a robust mini‐max filter. A numerical example shows the validity of this design.
Viral Infection: A Potent Barrier to Transplantation Tolerance
Authors: Miller David M. , Thornley Thomas B. , Greiner Dale L. , Rossini Aldo A.
Published: September 2008

Transplantation of allogeneic organs has proven to be an effective therapeutic for a large variety of disease states, but the chronic immunosuppression that is required for organ allograft survival increases the risk for infection and neoplasia and has direct organ toxicity. The establishment of transplantation tolerance, which obviates the need for chronic immunosuppression, is the ultimate goal in the field of transplantation. Many experimental approaches have been developed in animal models that permit long-term allograft survival in the absence of chronic immunosuppression. These approaches function by inducing peripheral or central tolerance to the allograft. Emerging as some of the most promising approaches for the induction of tolerance are protocols based on costimulation blockade. However, as these protocols move into the clinic, there is recognition that little is known as to their safety and efficacy when confronted with environmental perturbants such as virus infection. In animal models, it has been reported that virus infection can prevent the induction of tolerance by costimulation blockade and, in at least one experimental protocol, can lead to significant morbidity and mortality. In this review, we discuss how viruses modulate the induction and maintenance of transplantation tolerance.
Service‐Oriented Synthesis of Distributed and Concurrent Protocol Specifications
Authors: Al Dallal Jehad , Saleh Kassem
Published: September 2008

Several methods have been proposed for synthesizing computer communication protocol specifications from service specifications. Some protocol synthesis methods based on the finite state machine (FSM) model assume that primitives in the service specifications cannot be executed simultaneously. Others either handle only controlled primitive concurrency or have tight restrictions on the applicable FSM topologies. As a result, these synthesis methods are not applicable to an interesting variety of inherently concurrent applications, such as the Internet and mobile communication systems. This paper proposes a concurrent‐based protocol synthesis method that eliminates the restrictions imposed by the earlier methods. The proposed method uses a synthesis method to obtain a sequential protocol specification (P‐SPEC) from a given service specification (S‐SPEC). The resulting P‐SPEC is then remodeled to consider the concurrency behavior specified in the S‐SPEC, while guaranteeing that P‐SPEC provides the specified service.
Angina in Fabry Disease Reflects Coronary Small Vessel Disease
Authors: Chimenti Cristina , Morgante Emanuela , Tanzilli Gaetano , Mangieri Enrico , Critelli Giuseppe , Gaudio Carlo , Russo Matteo A. , Frustaci Andrea
Published: September 2008

Background—

Chest pain is frequently reported in Fabry disease (FD). However, its mechanism and clinical relevance are unclear.

Methods and Results—

Basal troponin I level, exercise stress test, single-photon emission computed tomography imaging with
99m
Tc sestamibi, coronary angiography with thrombolysis in myocardial infarction (TIMI) frame count and left ventricular angiography and endomyocardial biopsy were obtained in 13 patients with FD with angina. Ratio of external to lumen diameter of intramural arteries (E/L ratio), myocyte diameter, and extent of fibrosis were morphometrically evaluated by using tissue sections. Controls for coronary angiography and histology were 25 patients with FD without angina and 20 mitral stenosis patients with normal left ventricular function. Troponin I level was elevated in 6 of the 13 patients. Exercise stress test showed evidence of myocardial ischemia, and single-photon emission computed tomography was positive for stress-induced perfusion defects in all patients with FD with angina. Epicardial coronaries were structurally normal but showed slow flow in all and were associated with aneurisms of posterior left ventricular wall in 3 cases. Histology showed remarkable lumen narrowing of most intramural arteries (mean E/L ratio=3.5�1.2;
P
<0.001 versus both control groups), because of hypertrophy and proliferation of smooth muscle and endothelial cells, both engulfed by glycosphingolipids. Replacement fibrosis exceeded that of both controls (
P
<0.001). Small vessel disease correlated with coronary slow flow and extent of fibrosis, but did not with patients’ age, sex, and degree of left ventricular hypertrophy.

Conclusions—

patients with FD with angina have perfusion defects, slow coronary flow, and luminal narrowing of intramural arteries. Small vessel disease may contribute to symptomatic limitation and progressive myocardial dysfunction.
Value of Clinician Assessment of Hemodynamics in Advanced Heart Failure
Authors: Drazner Mark H. , Hellkamp Anne S. , Leier Carl V. , Shah Monica R. , Miller Leslie W. , Russell Stuart D. , Young James B. , Califf Robert M. , Nohria Anju
Published: September 2008

Background—

We determined whether estimated hemodynamics from history and physical examination (H&P) reflect invasive measurements and predict outcomes in advanced heart failure. The role of the H&P in medical decision making has declined in favor of diagnostic tests, perhaps because of the lack of evidence for utility.

Methods and Results—

We compared H&P estimates of filling pressures and cardiac index with invasive measurements in 194 patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. H&P estimates were compared with 6-month outcomes in 388 patients enrolled in ESCAPE. Measured right atrial pressure was <8 mm Hg in 82% of patients with right atrial pressure estimated from jugular veins as <8 mm Hg, and was >12 mm Hg in 70% of patients when estimated as >12 mm Hg. From the H&P, only estimated right atrial pressure ≥12 mm Hg (odds ratio, 4.6;
P
<0.001) and orthopnea ≥2 pillows (odds ratio, 3.6;
P
<0.05) were associated with pulmonary capillary wedge pressure ≥30 mm Hg. Estimated cardiac index did not reliably reflect the measured cardiac index (
P
=0.09), but “cold” versus “warm” profile was associated with lower median measured cardiac index (1.75 versus 2.0 L/(min�m
2
);
P
=0.004). In Cox regression analysis, discharge “cold” or “wet” profile conveyed a 50% increased risk of death or rehospitalization.

Conclusions—

In advanced heart failure, the presence of orthopnea and increased jugular venous pressure is useful to detect increased pulmonary capillary wedge pressure, and a global assessment of inadequate perfusion (“cold” profile) is useful to detect reduced cardiac index. Hemodynamic profiles estimated from the discharge H&P identify patients at increased risk of early events.
Patent Foramen Ovale and Migraine
Authors: Rundek Tatjana , Elkind Mitchell S.V. , Di Tullio Marco R. , Carrera Emmanuel , Jin Zhezhen , Sacco Ralph L. , Homma Shunichi
Published: September 2008

Background—

A causal relationship between patent foramen ovale (PFO) and migraine has been hypothesized, and improvement of migraine frequency and severity after percutaneous PFO closure has been reported. Population-based data on the relationship between PFO and migraine are sparse, however. The objective of this study was to examine the association between PFO and migraine among stroke-free individuals in an urban, population-based, multiethnic cohort.

Methods and Results—

As a part of the ongoing Northern Manhattan Study (NOMAS), 1101 stroke-free subjects were assessed for self-reported history of migraine. The presence of PFO was assessed by transthoracic echocardiography. The mean age of the group was 69±10 years; 58% were women. Forty-eight percent were Caribbean Hispanic, 24% were white, 26% were black, and 2% were another race/ethnicity. The prevalence of self-reported migraine was 16% (13% migraine with aura). The prevalence of PFO was 15%. Migraine was significantly more frequent among younger subjects, women, and Hispanics. The prevalence of PFO was not significantly different between subjects who had migraine (26/178, or 14.6%) and those who did not (138/923, or 15.0%;
P
=0.9). In an adjusted multivariate logistic regression model, the presence of PFO was not associated with increased prevalence of migraine (odds ratio 1.01, 95% confidence interval 0.63 to 1.61). Increasing age was associated with lower prevalence of migraine in both subjects with a PFO (odds ratio 0.94, 95% confidence interval 0.90 to 0.99 per year) and those without PFO (odds ratio 0.97, 95% confidence interval 0.95 to 0.99 per year). The observed lack of association between PFO and migraine (with or without aura) was not modified by diabetes mellitus, hypertension, cigarette smoking, or dyslipidemia.

Conclusions—

In this multiethnic, elderly, population-based cohort, PFO detected with transthoracic echocardiography and agitated saline was not associated with self-reported migraine. The causal relationship between PFO and migraine remains uncertain, and the role of PFO closure among unselected patients with migraine remains questionable.
Activation of Liver X Receptors Promotes Neuroprotection and Reduces Brain Inflammation in Experimental Stroke
Authors: Morales Jesús R. , Ballesteros Iván , Deniz José Manuel , Hurtado Olivia , Vivancos José , Nombela Florentino , Lizasoain Ignacio , Castrillo Antonio , Moro María A.
Published: September 2008

Background—

The liver X receptors (LXRs) belong to the nuclear receptor superfamily and act as transcriptional regulators of cholesterol metabolism in several tissues. Recent work also has identified LXRs as potent antiinflammatory molecules in macrophages and other immune cells. Combined changes in lipid and inflammatory profiles are likely mediating the protective role of LXRs in models of chronic injury like atherosclerosis. These beneficial actions, however, have not been illustrated in other models of acute injury such as stroke in which inflammation is an important pathophysiological feature.

Methods and Results—

We have studied LXR expression and function in the course of experimental stroke caused by permanent middle cerebral artery occlusion in rats and mice. Here, we show that administration of the synthetic LXR agonists GW3965 or TO901317 after the ischemic occlusion improves stroke outcome as shown by decreased infarct volume area and better neurological scores in rats. Neuroprotection observed with LXR agonists correlated with decreased expression of proinflammatory genes in the brain and with reduced nuclear factor-κB transcriptional activity. Loss of function studies using LXRα,β
−/−
mice demonstrated that the effect of LXR agonists is receptor specific. Interestingly, infarcted brain area and inflammatory signaling were significantly extended in LXRα,β
−/−
mice compared with control animals, indicating that endogenous LXR signaling mediates neuroprotection in this setting.

Conclusion—

This work highlights the transcriptional action of LXR as a protective pathway in brain injury and the potential use of LXR agonists as therapeutic agents in stroke.
Transition From Chronic Compensated to Acute Decompensated Heart Failure
Authors: Zile Michael R. , Bennett Tom D. , St. John Sutton Martin , Cho Yong K. , Adamson Philip B. , Aaron Mark F. , Aranda Juan M. , Abraham William T. , Smart Frank W. , Stevenson Lynne Warner , Kueffer Fred J. , Bourge Robert C.
Published: September 2008

Background—

Approximately half of all patients with chronic heart failure (HF) have a decreased ejection fraction (EF) (systolic HF [SHF]); the other half have HF with a normal EF (diastolic HF [DHF]). However, the underlying pathophysiological differences between DHF and SHF patients are incompletely defined. The purpose of this study was to use echocardiographic and implantable hemodynamic monitor data to examine the pathophysiology of chronic compensated and acute decompensated HF in SHF versus DHF patients.

Methods and Results—

Patients were divided into 2 subgroups: 204 had EF <50% (SHF) and 70 had EF ≥50% (DHF). DHF patients had EF of 58±8%, end-diastolic dimension of 50±10 mm, estimated resting pulmonary artery diastolic pressure (ePAD) of 16±9 mm Hg, and diastolic distensibility index (ratio of ePAD to end-diastolic volume) of 0.11±0.06 mm Hg/mL. In contrast, SHF patients had EF of 24±10%, end-diastolic dimension of 68±11 mm, ePAD of 18±7 mm Hg, and diastolic distensibility index of 0.06±0.04 mm Hg/mL (
P
<0.05 versus DHF for all variables except ePAD). In SHF and DHF patients who developed acute decompensated HF, these events were associated with a significant increase in ePAD, from 17±7 to 22±7 mm Hg (
P
<0.05) in DHF and from 21±9 to 24±8 mm Hg (
P
<0.05) in SHF. As a group, patients who did not have acute decompensated HF events had no significant changes in ePAD.

Conclusions—

Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.
Association Between Different Measures of Blood Pressure and Coronary Artery Calcium in Postmenopausal Women
Authors: Allison Matthew A. , Manson JoAnn E. , Langer Robert D. , Aragaki Aaron , Smoller Sylvia , Lewis Cora E. , Thomas Asha , Lawson William , Cochrane Barbara B. , Hsia Judith , Hunt Julie R. , Robinson Jennifer
Published: September 2008

The aim of this study was to determine the magnitude and significance of the associations among coronary artery calcium (CAC) and systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure. Women 50 to 59 years of age at baseline in the Women’s Health Initiative clinical trial of conjugated equine estrogen underwent computed tomography scanning of the chest after the end of the trial. Blood pressures were measured twice with the participant in the seated position using a conventional mercury sphygmomanometer. The study included 1064 women with a mean age of 55.1 (2.8) years. The prevalence of a CAC score >0, ≥10, and >100 was 47%, 39%, and 19%, respectively. There was a linear association between the log-odds of any CAC and systolic blood pressure, whereas there was a curvilinear and inverse association with diastolic blood pressure. For any value of diastolic blood pressure, the probability of CAC increased with higher levels of systolic blood pressure, whereas for any given value of systolic blood pressure, the probability of any CAC decreased with higher levels of diastolic blood pressure. Also, a pulse pressure ≥55 mm Hg was associated with a higher odds (1.95; 95% CI, 1.24 to 3.06) for having any CAC, whereas individuals with isolated systolic hypertension had a 73% higher odds for CAC >0 (95% CI, 1.03 to 2.90;
P
=0.04). In postmenopausal women, higher levels of pulse pressure and systolic blood pressure were strong determinants of CAC, whereas diastolic blood pressure was inversely related.
Children and Religion under Article 14 UNCRC: A Critical Analysis
Authors: Langlaude Sylvie
Published: September 2008

This article examines the text of Article 14 of the UN Convention on the Rights of the Child 1989 and the work of the UN Committee on the Rights of the Child. It considers the text of the Article and its travaux préparatoires; it then provides an analysis of the issues considered by the Committee: the concept of the evolving capacities of the child, freedom of religious choice, freedom of manifestation, and education. It also highlights the problems that have emerged in the Committee's work, in the light of a theoretical framework of the right of the child to religious freedom in international law. It concludes that the Committee fails children in relation to their religion and suggests some positive steps to be taken by the Committee.
Kabbalah, Philosophy, and the Jewish-Christian Debate: Reconsidering the Early Works of Joseph Gikatilla
Authors: Lachter Hartley
Published: September 2008

Joseph Gikatilla's early works, composed during the 1270s, have been understood by many scholars as a fusion of Kabbalah and philosophy—an approach that he abandoned in his later compositions. This paper argues that Gikatilla's early works are in fact consistent with his later works, and that the differences between the two can be explained by the polemical engagement during his early period with Jewish philosophy and Christian missionizing. By subtly drawing Jewish students of philosophy away from Aristotelian speculation and towards Kabbalah, Gikatilla sought in his early works to lay the foundation for an understanding of Judaism based on kabbalistic mytho-poesis and ecstatic mystical experience.
The ‘Returns to Religion’: Messianism, Christianity and the Revolutionary Tradition. Part II: The Pauline Tradition
Authors: Roberts John
Published: September 2008

The central strength of the Hegelian dialectical tradition is that reason is not divorced from its own internal limits in the name of a reason free from ideological mediation and constraint. This article holds onto this insight in the examination of the recent (and widespread) returns to religious categories in political philosophy and political theory (in particular Agamben, Badiou, Negri and Žižek). In this it follows a twofold logic. In the spirit of Hegel and Marx it seeks to recover what is ‘rational in religion’; at the same time, it examines the continuing entanglements of politics (and specifically revolutionary thinking) with religious categories. That this is an atheistic and materialist project is not in a sense strange or anomalous. On the contrary, it is precisely the ‘secularisation’ of Judeo-Christian categories in Kant, Hegel and Marx's respective theorisations of history that provides the dialectical ground for the atheistic recovery and invocation of Judeo-Christian thought (in particular messianism, renunciation, and fidelity) in recent political philosophy. Consequently, this discussion of religion, or ‘religion beyond religion’, has very little to do with the spread of obscurantism and anti-rationalism in the global upsurge of reactionary Christian and Islamic fundamentalisms, neo-pagan mysticisms, and other retreats from the real, or with the left-liberal denunciation of religion in the recent writings of Richard Dawkins and Christopher Hitchens. Rather, ‘religion’ here, in its Judeo-Christian legacy, is that which embodies the memory or prospect of a universal emancipatory politics.
Prisons et autorités urbaines sous les Abbassides
Authors: Tillier Mathieu
Published: September 2008

Deux catégories de prisons coexistaient à l'époque abbasside : celles des cadis et celles d'institutions politico-militaires. Mais cette distinction était largement théorique. L'étude de l'administration carcérale, de ses rapports aux autorités urbaines et de sa géographie montre que les prisons relevaient avant tout des gouverneurs et de la šurta : par leur empreinte sur le paysage urbain, les principales prisons iraqiennes manifestaient la puissance coercitive de la dynastie. Two kinds of prisons coexisted under the ‘Abbāsids: the qādī's prisons and those of some military as well as political institutions. But the distinction was largely theoretical. The study of their administration, of their relations with the urban authorities and of their location shows that prisons depended above all on governors and šurta: by impressing their stamp on the urban landscape, the main Iraqi prisons expressed the coercive power of the dynasty.
Medical Research on Minors in Finland
Authors: Lötjönen Salla
Published: September 2008

This article concerns the legal regulation of medical research on children in Finland. The topic is covered by the Medical Research Act of 1999 and by the Recommendations issued by the Working group on medical research on children in 2003. The Decisions of the Parliamentary Ombudsman also play an important role in this area in Finland. The article focuses on two specific issues: involvement of guardians in decision-making for the child, and the expansion of the right to self-determination of minors. Two case examples on these topics are also discussed. Overall, the author comes to the conclusion that the Finnish legislation, policy-makers, investigators and the industry have succeeded well in taking into account international legislation in this area, although there is also room for improvement.
The Implementation of Directive 2001/20/EC into Belgian Law and the Specific Provisions on Pediatric Research
Authors: Nys Herman , Dierickx Kris , Pinxten Wim
Published: September 2008

The European Clinical Trial Directive (2001/20/EC) was implemented into the Belgian legal system by the Law of 7 May 2004 concerning experiments on the human person (LEH). Apart from implementing the European Directive, this law also broadens the scope of the Directive from interventional clinical trials to all medical experiments involving human persons. This article offers an overview of the requirements for involving minors in medical experiments that are captured in the LEH, illustrates the process of protocol review by an ethics committee, and discusses the dissimilarities between the LEH and the European Directive.
Measuring Children's Rights: An Alternative Approach
Authors: Carvalho Edzia
Published: September 2008

The rights of the child, as recognised by the United Nations Convention on the Rights of the Child have been increasingly reiterated in international declarations and national commitments. However, there exists a disparity in ‘the de jure protection and de facto realization of human rights’ (Landman 2005: 5). The relative absence of systematic engagement within academia and without on the issue of mapping the operationalisation of children's rights by States not only hinders ongoing attempts to identify and explain the causes and variation in the failure to implement children's rights but also weakens national and international efforts to hold States accountable for their obligations. This article seeks to address the lack of utilisation of measures of children's rights and the deficiencies in the measures that are in use. By drawing on the existing academic literature and intergovernmental efforts to measure human rights, the article proposes a measurement matrix that could be used to chart the implementation of States' obligations towards children's rights. The matrix is an attempt to further the emerging international endeavours to develop children's rights indicators.
Human Rights in Light of Childhood
Authors: Wall John
Published: September 2008

This essay argues that children's rights will adequately transform societies only when the very concept of “human rights” is reimagined in light of childhood. In this case, human rights would be understood as grounded, not in modernist ideas of autonomy, liberty, entitlement, or even agency, but in a postmodern circle of responsibility to one another. This “childist” interpretation of rights is constructed by examining various forms of child-centered ethical theory in Western history; their impacts on major human rights theories of the Enlightenment and today; alternative visions implied in twentieth century international children's rights agreements; new theoretical groundings arising out of postmodern ethics; and the possibility of human rights as truly including all humanity.
Simulated Anthropogenic Changes in the Brewer–Dobson Circulation, Including Its Extension to High Latitudes
Authors: McLandress Charles , Shepherd Theodore G.
Published: September 2008

Recent studies using comprehensive middle atmosphere models predict a strengthening of the Brewer–Dobson circulation in response to climate change. To gain confidence in the realism of this result it is important to quantify and understand the contributions from the different components of stratospheric wave drag that cause this increase. Such an analysis is performed here using three 150-yr transient simulations from the Canadian Middle Atmosphere Model (CMAM), a Chemistry–Climate Model that simulates climate change and ozone depletion and recovery. Resolved wave drag and parameterized orographic gravity wave drag account for 60% and 40%, respectively, of the long-term trend in annual mean net upward mass flux at 70 hPa, with planetary waves accounting for 60% of the resolved wave drag trend. Synoptic wave drag has the strongest impact in northern winter, where it accounts for nearly as much of the upward mass flux trend as planetary wave drag. Owing to differences in the latitudinal structure of the wave drag changes, the relative contribution of resolved and parameterized wave drag to the tropical upward mass flux trend over any particular latitude range is highly sensitive to the range of latitudes considered. An examination of the spatial structure of the climate change response reveals no straightforward connection between the low-latitude and high-latitude changes: while the model results show an increase in Arctic downwelling in winter, they also show a decrease in Antarctic downwelling in spring. Both changes are attributed to changes in the flux of stationary planetary wave activity into the stratosphere.
Cause or Consequence?
Authors: Jargowsky Paul A. , Park Yoonhwan
Published: September 2008

Inner-city crime is a motivating factor for middle-class flight. Therefore, crime is a cause of suburbanization. Movement of the middle and upper classes to the suburbs, in turn, isolates the poor in central-city ghettos and barrios. Sociologists and criminologists have argued that the concentration of poverty creates an environment within which criminal behavior becomes normative, leading impressionable youth to adopt criminal lifestyles. Moreover, from the perspective of routine activity theory, the deterioration of social capital in high-poverty areas reduces the capacity for guardianship. Therefore, suburbanization may also cause crime. The authors argue that prior research has not distinguished between the causal and compositional effects of suburbanization on crime. They show that the causal component can be identified by linking metropolitan-level crime rates, rather than central-city crime rates, to measures of suburbanization. Using Uniform Crime Reports and census data from 2000, they find a positive relationship between suburbanization and metropolitan crime.