bluuebunny/crossref_metadata_2025 huggingface dataset:
The Phenion® Full-Thickness Skin Model for Percutaneous Absorption Testing
Authors: Ackermann K. , Lombardi Borgia S. , Korting H.C. , Mewes K.R. , Schäfer-Korting M.
Published: December 2009

In recent years many efforts have been made to replace dermal toxicity testing of chemicals in the animal by in vitro assays. As a member of a German research consortium, we have previously contributed to the validation of an in vitro test protocol for percutaneous absorption studies on the basis of reconstructed human epidermis and both human and pig skin ex vivo. Aiming to assess the barrier properties of a newly developed reconstructed skin model, this protocol has now been transferred to the Phenion® Full-Thickness Skin Model (FT model). The permeation of testosterone and caffeine was quantified in parallel to that of pig skin using Franz-type diffusion cells. In addition, the permeation of benzoic acid and nicotine was studied. As expected, the FT model is more permeable than pig skin, yet its barrier properties are well in accordance with those of reconstructed human epidermis when compared to previous data. In fact, the FT model most efficiently retards testosterone as the compound of highest lipophilicity, which can be explained by an additional uptake by a reservoir formed by the dermis equivalent. Thus, the structure closely parallels human skin. In consequence, the Phenion FT model appears to be suitable for percutaneous absorption studies in hazard analysis and should be subjected to a catch-up validation study.
Ameliorative Effects of Stabilized Rice Bran on Type 2 Diabetes Patients
Authors: Cheng Hsing-Hsien , Huang Hsin-Yi , Chen Ya-Yen , Huang Chen-Ling , Chang Chun-Jen , Chen Hsiao-Lien , Lai Ming-Hoang
Published: December 2009

Background/Aim: While it has been demonstrated that rice bran might lower the cholesterol level in hypercholesterolemic individuals, its effects on the levels of adiponectin and glycated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus remain unknown. Methods: Twenty-eight volunteers with type 2 diabetes were randomly divided into 2 groups, one of which received a dietary supplement of 20 g of stabilized rice bran and the other placebo once daily for 12 weeks. Parameters such as the level of HbA1c, glucose, insulin, homeostasis model assessment for estimation of relative insulin resistance, high-density and low-density lipoprotein (LDL) cholesterol and adiponectin were evaluated. Results: At the end of the study period, postprandial glucose and the area under the glucose curve of the rice bran group were significantly lower than baseline levels by 14.4 and 15.7%, respectively. Compared to baseline, the HbA1c values in the rice bran group were also significantly lower. Serum total cholesterol and LDL cholesterol concentrations in the rice bran group were 9.2 and 13.7% lower, respectively, than in the placebo group. The plasma free fatty acid and adiponectin concentrations were 20% lower and 40% higher in the rice bran group compared to the placebo group. Conclusions: This study demonstrated that stabilized rice bran can lower the level of HbA1c and blood lipids and increase blood adiponectin concentrations in type 2 diabetic subjects. In light of this, we conclude that stabilized rice bran may represent an important functional nutrient to ameliorate lipid and glycemic anomalies in type 2 diabetic subjects.
Oxaliplatin-Induced Lhermitte’s Phenomenon as a Manifestation of Severe Generalized Neurotoxicity
Authors: Park Susanna B. , Lin Cindy S.-Y. , Krishnan Arun V. , Goldstein David , Friedlander Michael L. , Kiernan Matthew C.
Published: December 2009

Objectives: Lhermitte’s phenomenon, characterized by ‘electric-shock’ sensations precipitated by neck flexion, may develop during oxaliplatin treatment. Limited cases have been described previously and the pathophysiology underlying Lhermitte’s phenomenon in oxaliplatin-treated patients has not been established. Methods: Patients who developed Lhermitte’s phenomenon during oxaliplatin therapy were investigated by neurological examination, neurotoxicity grading and conventional nerve conduction studies (NCS). Structural (magnetic resonance imaging) and functional (somatosensory evoked potentials) spinal assessment was also undertaken. Sensory nerve excitability recordings were performed longitudinally across treatment to investigate ion channel function. Results: Five oxaliplatin-treated patients reported Lhermitte’s phenomenon, with a mean cumulative dose of 861 ± 84 mg/m2 oxaliplatin (range 574–1,100 mg/m2). NCS revealed severe sensory neuropathy in all patients. There was no evidence of structural or functional spinal cord damage. Nerve excitability studies revealed progressive alterations in sensory excitability throughout treatment, consistent with oxaliplatin-induced nerve dysfunction. In patients with Lhermitte’s phenomenon, refractoriness was reduced to –14.4% (confidence interval, CI: –20.5 to –8.4%) by late treatment, a significantly greater reduction than in oxaliplatin-treated patients who did not develop Lhermitte’s phenomenon (–2.7%; CI: –7.6 to 2.2; p = 0.013). Conclusions: Lhermitte’s phenomenon represents a severe presentation of oxaliplatin-induced neurotoxicity, associated with generalized nerve dysfunction in the absence of structural spinal abnormalities.
On the Origin of Planetary-Scale Extratropical Winter Circulation Regimes
Authors: Hannachi A.
Published: December 2009

Sectorial and planetary-scale winter circulation regimes are studied and the relationship between them is investigated in order to find how much the simultaneous occurrence of sectorial regimes contributes to the occurrence of hemispheric regimes. The strategy is based on the multivariate Gaussian mixture model. The number of components in the model is estimated using two approaches. The first one is based on arguments from order statistics of the mixture proportions and the second uses a more severe test based on reproducibility. The procedure is applied next to the 500-hPa height field over the North Pacific, the North Atlantic, and the Northern Hemisphere using the empirical orthogonal function state space. Two highly significant regimes are found in each case, namely, the Pacific–North America (pattern) (±PNA)–North Atlantic Oscillation (±NAO) for the hemisphere—±PNA for the Pacific sector and ±NAO for the Atlantic sector. The sectorial regimes reflect mainly blocking and no-blocking flows. The results are tested further by applying a spatial clustering algorithm and are found to be consistent, particularly along the regime axes in the system state space. The relationship between hemispheric and sectorial circulation regimes is investigated. The data in each sector are first classified and then the times of simultaneous occurrence of sectorial regimes are identified. A new hemispheric dataset is then obtained by discarding maps corresponding to those co-occurrence times, and a new regime analysis is conducted. The results show that the hemispheric regime behavior has significantly decreased, suggesting that synchronization between sectorial circulation regimes could play an important role in the occurrence of planetary circulation regimes. The interannual variability of regime events is also discussed.
Relationships between Upper-Level Circulation over South America and Rainfall over Southeastern South America: A Physical Base for Seasonal Predictions
Authors: Zamboni Laura , Mechoso Carlos R. , Kucharski Fred
Published: December 2009

The existence of a significant simultaneous correlation between bimonthly mean precipitation anomalies over southeastern South America (SESA) and either the first or the second (depending on season) leading mode of interannual variability of upper-level wind over South America (SA) is demonstrated during all seasons except winter. The pattern associated with these modes of variability is similar during all seasons and consists of a continental-scale vortex centered over the eastern coast of subtropical SA. The vortex has a quasi-barotropic structure during all seasons, and its variability modifies moisture transport from the South American low-level jet and the western tropical Atlantic to SESA thus creating precipitation anomalies in this region. During spring (October–November) and summer (January–February) the circulation creates a second center of precipitation anomalies over the South Atlantic convergence zone that are of opposite sign to those over SESA, while during fall (April–May) precipitation anomalies are primarily confined to SESA. On the basis of the correlation between upper-level winds and precipitation, an empirical method to produce long-range forecasts of bimonthly mean precipitation over SESA is developed. Method tests in hindcast mode for the period 1959–2001 show a potential for reliable predictions during the southern spring, summer, and fall. The method is further tested in an experimental mode by using Development of a European Multimodel Ensemble System for Seasonal-to-Interannual Prediction (DEMETER) wind hindcasts. Forecasts obtained in this way are skillful during spring only, with highest skill during El Niño–Southern Oscillation years. During summer and fall, the DEMETER forecasts of wind anomalies limit the method’s ability to make reliable real predictions.
The Sensitivity of Latent Heat Flux to Changes in the Radiative Forcing: A Framework for Comparing Models and Observations
Authors: Winter Jonathan M. , Eltahir Elfatih A. B.
Published: December 2009

A climate model must include an accurate surface physics scheme in order to examine the interactions between the land and atmosphere. Given an increase in the surface radiative forcing, the sensitivity of latent heat flux to available energy plays an important role in determining the energy budget and has a significant impact on the response of surface temperature.

The Penman–Monteith equation is used to construct a theoretical framework for evaluating the climatology of evapotranspiration and the sensitivity of latent heat flux to available energy. Regional Climate Model version 3 coupled to Integrated Biosphere Simulator (RegCM3–IBIS); RegCM3 with its native land surface model, Biosphere–Atmosphere Transfer Scheme 1e (RegCM3–BATS1e); and Flux Network (FLUXNET) micrometeorological tower observations are compared and contrasted using the developed methodology.

RegCM3–IBIS and RegCM3–BATS1e simulate the observed sensitivity of latent heat flux to available energy reasonably well during the summer on average; however, there are significant variations in the monthly values. Additional information provided by the physically based Penman–Monteith framework is employed for identifying deficiencies and guiding improvements in models, allowing calibration of both the climatology of evapotranspiration and the sensitivity of latent heat flux to available energy.
Seasonal Variations of the Synoptic-Scale Transient Eddy Activity and Polar Front Jet over East Asia
Authors: Ren Xuejuan , Yang Xiuqun , Chu Cuijiao
Published: December 2009

Seasonal variations of the synoptic-scale transient eddy activity (STEA) and the jet streams over East Asia are examined through analysis of the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) data. Extracted from the 6-hourly upper-level wind fields, the distribution of the jet core numbers exhibits a distinct geographical border for the East Asian subtropical jet (EASJ) and the East Asian polar front jet (EAPJ) at the latitudes of the northern Tibetan Plateau (TP). In the cool seasons, two branches of the STEA and low-level baroclinicity exist over the East Asian landmass, accompanied by the two-jet state of the EASJ and EAPJ. In the warm seasons, a single jet pattern of the EASJ along the north flank of the TP is accompanied by the weakened STEA over the mid- to high latitudes of East Asia. Further analysis shows two distinct features of the seasonal variations of the STEA over East Asia, compared with that over the North Pacific. First, during the transitional period of April–June, the main STEA band over East Asia migrates northward dramatically, in conjunction with the EAPJ shifting in the same direction. Second, both the upper-level STEA and the lower-level baroclinicity poleward of the TP are prosperous in spring. The relationship between the STEA, baroclinicity, vertical wind shear, and static stability in the EAPJ region in different seasons is further investigated. It is found that in addition to the time-mean wind fields, the rapid increase in the sensible heat flux poleward side of the TP region in spring and the associated boundary layer processes are partially responsible for the spring prosperity of the local baroclinicity and the STEA.
Error Propagation of Remote Sensing Rainfall Estimates in Soil Moisture Prediction from a Land Surface Model
Authors: Serpetzoglou Efthymios , Anagnostou Emmanouil N. , Papadopoulos Anastasios , Nikolopoulos Efthymios I. , Maggioni Viviana
Published: December 2009

The study presents an in-depth investigation of the properties of remotely sensed rainfall error propagation in the prediction of near-surface soil moisture from a land surface model (LSM). Specifically, two error sources are compared: rainfall forcing due to estimation error by remote sensing techniques and the representation of land–atmospheric processes due to LSM uncertainty [the Community Land Model, version 3.5 (CLM3.5), was used in this particular study]. CLM3.5 is forced by three remotely sensed precipitation products, namely, two satellite-based estimates—NASA’s Tropical Rainfall Measuring Mission (TRMM) multisatellite precipitation analysis and NOAA’s Climate Prediction Center morphing technique (CMORPH)—and a rain gauge-adjusted radar–rainfall product from the Weather Surveillance Radar-1988 Doppler (WSR-88D) network. The error analysis is performed for the warm seasons of 2004 and 2006 and is facilitated through the use of in situ measurements of soil moisture, rainfall, and other meteorological variables from a network of stations capturing the state of Oklahoma (Oklahoma Mesonet). The study also presents a rigorous benchmarking of the Mesonet network as to its accuracy in deriving area rainfall estimates at the resolution of satellite products (0.25° and 3 h) through comparisons against the most definitive measurements of a smaller-yet-denser network of rain gauges in southwestern Oklahoma (Micronet). The study compares error statistics between modeling and precipitation error sources and between the various remote sensing techniques. Results are contrasted between the relatively moist summer period of 2004 to the drier summer period of 2006, indicating model and error propagation dependencies. An intercomparison between rainfall and modeling error shows that the two error sources are of similar magnitudes in the case of high modeling accuracy (i.e., 2004), whereas the contribution of rainfall forcing error to the uncertainty of soil moisture prediction can be lower when the model’s efficiency skill is relatively low (i.e., 2006).
Modal Interpretation for the Ekman Destabilization of Inviscidly Stable Baroclinic Flow in the Phillips Model
Authors: Swaters Gordon E.
Published: December 2009

Ekman boundary layers can lead to the destabilization of baroclinic flow in the Phillips model that, in the absence of dissipation, is nonlinearly stable in the sense of Liapunov. It is shown that the Ekman-induced instability of inviscidly stable baroclinic flow in the Phillips model occurs if and only if the kinematic phase velocity associated with the dissipation lies outside the interval bounded by the greatest and least neutrally stable Rossby wave phase velocities. Thus, Ekman-induced destabilization does not correspond to a coalescence of the barotropic and baroclinic Rossby modes as in classical inviscid baroclinic instability. The differing modal mechanisms between the two instability processes is the reason why subcritical baroclinic shears in the classical theory can be destabilized by an Ekman layer, even in the zero dissipation limit of the theory.
Stable Shallow Water Vortices over Localized Topography
Authors: Iacono Roberto
Published: December 2009

It is shown that a sufficient condition for stability by P. Ripa, based on the monotonicity of the flow potential vorticity (PV), can be used to prove linear stability of isolated shallow water vortices over localized topographic features. Stable axisymmetric vortices over axisymmetric topography that satisfy Ripa’s condition are explicitly constructed by using a simple two-step, fully analytic approach. First, for a given velocity profile, the topography is found that yields a steady-state, constant-PV solution of the shallow water equations. Then, this topography is slightly modified to obtain new steady solutions, with monotonic PV, that satisfy Ripa’s stability criterion. Application of this procedure shows that modest depressions (elevations) can stabilize cyclones (anticyclones) with small Rossby and large Burger numbers and velocity profiles similar to those observed in mesoscale oceanic vortices. The stabilizing topographic features have radial sizes comparable with that of the vortex (about twice the radius of maximum speed) and maximum vertical size, normalized to the unperturbed fluid depth, from 2 to 3.3 times the Rossby number for the profiles considered. The upper limit corresponds to a Gaussian profile, whereas the lower limit is approached by a velocity profile that is linear inside the vortex core and a cubic polynomial outside.

Finally, it is argued that a similar stabilization mechanism holds for two-dimensional (2D) flows, and a method for the construction of stable 2D shallow water vortices over 2D topography is outlined that is analogous to that used for the axisymmetric problem. In the 2D case, however, it is generally not possible to obtain stable equilibria analytically.
Improving Policy for Stormwater Management: Implications for Climate Change Adaptation
Authors: Tryhorn Lee
Published: December 2009

Lack of local information on climate change impacts is increasingly recognized as an important barrier to progress in adaptation. However, simply providing decision makers with higher-resolution climate information will not ensure successful adaptation. In order for there to be appropriate information uptake and use, it is essential to understand the political constraints and conditions under which decision makers operate. A detailed examination of the current regulatory context in relation to climate and weather impacts can provide insight into the barriers and obstacles affecting decision makers in adaptation endeavors.

This study examines the experiences of the municipalities of Tompkins County, New York, as they attempt to manage stormwater in compliance with federally mandated regulations. The current policies fail to adequately address the fundamental problems affecting local government in New York: fragmented jurisdiction, interagency communication, inability to cope with unfunded mandates, enforcement, and the promotion of informed decision making. The way forward may be the adaptive governance approach for the management of complex environmental issues. This article is intended to serve as an initial model for other university-based researchers that are interested in serving their local communities with weather, climate, and policy research and are willing to engage in the complexities involved.
A Strategy for Risk Management of Drug-Induced Phospholipidosis
Authors: Chatman Linda A. , Morton Daniel , Johnson Theodore O. , Anway Susan D.
Published: December 2009

Drug-induced phospholipidosis (PL) is an excessive accumulation of phospholipids and drug in lysosomes. Phospholipidosis signals a change in cell membrane integrity and accumulation of intracellular drug or metabolite in tissues. The sensitivity and susceptibility of preclinical models to detect PL vary with therapeutic agents, and PL is expected to be reversible after discontinuation of drug treatment. The prevailing scientific opinion is that PL by itself is not adverse; however, some regulatory authorities consider PL to be adverse because a small number of chemicals are able to cause PL and concurrent organ toxicity. Until a greater understanding of PL emerges, a well-thought-out risk management strategy for PL will increase confidence in safety and improve selection and development of new drugs. This paper provides a tiered approach to risk management of drug-induced PL. It begins with use of in silico and in vitro tools to design and select compounds with reduced potential to produce PL. Early in vivo studies in two species are used to better characterize potential for toxicity and PL. Finally, routine risk management tools (i.e., translational biomarkers, assessment of reversibility) are used to support confidence in safety of compounds that induce PL in animals.
Evaluation of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder: a post hoc analysis of pooled data from short- and long-term aripiprazole trials
Authors: Kane John M , Barnes Thomas RE , Correll Christoph U , Sachs Gary , Buckley Peter , Eudicone James , McQuade Robert , Tran Quynh-Van , Pikalov Andrei , Assunção-Talbott Sheila
Published: December 2009

The objective of this article is to assess the clinical characteristics of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder receiving aripiprazole, haloperidol, olanzapine, or placebo. We conducted post hoc analyses of pooled safety data from trials in patients with schizophrenia, schizoaffective disorder, and bipolar I disorder. Outcome measures included the incidence of akathisia, time to onset, duration, severity, and discontinuation due to akathisia, concomitant use of benzodiazepines and/or anticholinergics, Barnes Akathisia Rating Scale (BARS) scores, and the correlation between antipsychotic efficacy and akathisia. The results for schizophrenia and schizoaffective disorder were as follows: akathisia in 9% of aripiprazole- and 6% of placebo-treated patients; 12.5% of aripiprazole- versus 24% of haloperidol-treated patients; 11% of aripiprazole- versus 6% of olanzapine-treated patients. Bipolar I disorder: akathisia in 18% of aripiprazole- and 5% of placebo-treated patients. The clinical characteristics of akathisia were similar between each data set, regardless of disease. Akathisia was generally mild-to-moderate in severity. Discontinuation due to akathisia was low in both the schizophrenia trials (aripiprazole 0.3%; placebo 0%; aripiprazole 0.9%; haloperidol 2.3%; aripiprazole 1.2%; olanzapine 0.2%) and the bipolar trials (aripiprazole 2.3%; placebo 0%). Treatment-emergent akathisia was not associated with a poorer clinical response. In conclusion, akathisia with aripiprazole occurred early in treatment, was mild-to-moderate in severity, led to few study discontinuations, and did not compromise therapeutic efficacy.
Utilization of the Natural Helper Model in Health Promotion Targeting African American Men
Authors: Scott Tiffany N.
Published: December 2009

When compared with other racial and ethnic groups, African American men experience a great number of health disparities. The factors that perpetuate health disparities among African American men are multidimensional and include lack of access to equitable health care, lack of knowledge and limited education about health promoting behaviors, lack of organizational trust and acceptability, the impact of masculinity on health, and psychological factors. This article explores the health promotion needs of African American men and the ability of the natural helper model to address those needs. Further discussion of its use by holistic nurses as a culturally tailored health promotion intervention targeting African American men is presented.
Constitutively active AKT depletes hematopoietic stem cells and induces leukemia in mice
Authors: Kharas Michael G. , Okabe Rachel , Ganis Jared J. , Gozo Maricel , Khandan Tulasi , Paktinat Mahnaz , Gilliland D. Gary , Gritsman Kira
Published: December 2009

Human cancers, including acute myeloid leukemia (AML), commonly display constitutive phosphoinositide 3-kinase (PI3K) AKT signaling. However, the exact role of AKT activation in leukemia and its effects on hematopoietic stem cells (HSCs) are poorly understood. Several members of the PI3K pathway, phosphatase and tensin homolog (Pten), the forkhead box, subgroup O (FOXO) transcription factors, and TSC1, have demonstrated functions in normal and leukemic stem cells but are rarely mutated in leukemia. We developed an activated allele of AKT1 that models increased signaling in normal and leukemic stem cells. In our murine bone marrow transplantation model using a myristoylated AKT1 (myr-AKT), recipients develop myeloproliferative disease, T-cell lymphoma, or AML. Analysis of the HSCs in myr-AKT mice reveals transient expansion and increased cycling, associated with impaired engraftment. myr-AKT–expressing bone marrow cells are unable to form cobblestones in long-term cocultures. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) rescues cobblestone formation in myr-AKT–expressing bone marrow cells and increases the survival of myr-AKT mice. This study demonstrates that enhanced AKT activation is an important mechanism of transformation in AML and that HSCs are highly sensitive to excess AKT/mTOR signaling.
Graphle: Interactive exploration of large, dense graphs
Authors: Huttenhower Curtis , Mehmood Sajid O , Troyanskaya Olga G
Published: December 2009

Background

A wide variety of biological data can be modeled as network structures, including experimental results (e.g. protein-protein interactions), computational predictions (e.g. functional interaction networks), or curated structures (e.g. the Gene Ontology). While several tools exist for visualizing large graphs at a global level or small graphs in detail, previous systems have generally not allowed interactive analysis of dense networks containing thousands of vertices at a level of detail useful for biologists. Investigators often wish to explore specific portions of such networks from a detailed, gene-specific perspective, and balancing this requirement with the networks' large size, complex structure, and rich metadata is a substantial computational challenge.

Results

Graphle is an online interface to large collections of arbitrary undirected, weighted graphs, each possibly containing tens of thousands of vertices (e.g. genes) and hundreds of millions of edges (e.g. interactions). These are stored on a centralized server and accessed efficiently through an interactive Java applet. The Graphle applet allows a user to examine specific portions of a graph, retrieving the relevant neighborhood around a set of query vertices (genes). This neighborhood can then be refined and modified interactively, and the results can be saved either as publication-quality images or as raw data for further analysis. The Graphle web site currently includes several hundred biological networks representing predicted functional relationships from three heterogeneous data integration systems: S. cerevisiae data from bioPIXIE, E. coli data using MEFIT, and H. sapiens data from HEFalMp.

Conclusions

Graphle serves as a search and visualization engine for biological networks, which can be managed locally (simplifying collaborative data sharing) and investigated remotely. The Graphle framework is freely downloadable and easily installed on new servers, allowing any lab to quickly set up a Graphle site from which their own biological network data can be shared online.
A changing picture of shigellosis in southern Vietnam: shifting species dominance, antimicrobial susceptibility and clinical presentation
Authors: Vinh Ha , Nhu Nguyen Thi Khanh , Nga Tran Vu Thieu , Duy Pham Thanh , Campbell James I , Hoang Nguyen Van Minh , Boni Maciej F , My Phan Vu Tra , Parry Christopher , Nga Tran Thi Thu , Van Minh Pham , Thuy Cao Thu , Diep To Song , Phuong Le Thi , Chinh Mai Thu , Loan Ha Thi , Tham Nguyen Thi Hong , Lanh Mai Ngoc , Mong Bui Li , Anh Vo Thi Cuc , Bay Phan Van Be , Chau Nguyen Van Vinh , Farrar Jeremy , Baker Stephen
Published: December 2009

Background

Shigellosis remains considerable public health problem in some developing countries. The nature of Shigellae suggests that they are highly adaptable when placed under selective pressure in a human population. This is demonstrated by variation and fluctuations in serotypes and antimicrobial resistance profile of organisms circulating in differing setting in endemic locations. Antimicrobial resistance in the genus Shigella is a constant threat, with reports of organisms in Asia being resistant to multiple antimicrobials and new generation therapies.

Methods

Here we compare microbiological, clinical and epidemiological data from patients with shigellosis over three different periods in southern Vietnam spanning14 years.

Results

Our data demonstrates a shift in dominant infecting species (S. flexneri to S. sonnei) and resistance profile of the organisms circulating in southern Vietnam. We find that there was no significant variation in the syndromes associated with either S. sonnei or S. flexneri, yet the clinical features of the disease are more severe in later observations.

Conclusions

Our findings show a change in clinical presentation of shigellosis in this setting, as the disease may be now more pronounced, this is concurrent with a change in antimicrobial resistance profile. These data highlight the socio-economic development of southern Vietnam and should guide future vaccine development and deployment strategies.

Trial Registration

Current Controlled Trials ISRCTN55945881
Nuclear receptor coregulator SNP discovery and impact on breast cancer risk
Authors: Hartmaier Ryan J , Tchatchou Sandrine , Richter Alexandra S , Wang Jay , McGuire Sean E , Skaar Todd C , Rae Jimmy M , Hemminki Kari , Sutter Christian , Ditsch Nina , Bugert Peter , Weber Bernhard HF , Niederacher Dieter , Arnold Norbert , Varon-Mateeva Raymonda , Wappenschmidt Barbara , Schmutzler Rita K , Meindl Alfons , Bartram Claus R , Burwinkel Barbara , Oesterreich Steffi
Published: December 2009

Background

Coregulator proteins are "master regulators", directing transcriptional and posttranscriptional regulation of many target genes, and are critical in many normal physiological processes, but also in hormone driven diseases, such as breast cancer. Little is known on how genetic changes in these genes impact disease development and progression. Thus, we set out to identify novel single nucleotide polymorphisms (SNPs) within SRC-1 (NCoA1), SRC-3 (NCoA3, AIB1), NCoR (NCoR1), and SMRT (NCoR2), and test the most promising SNPs for associations with breast cancer risk.

Methods

The identification of novel SNPs was accomplished by sequencing the coding regions of these genes in 96 apparently normal individuals (48 Caucasian Americans, 48 African Americans). To assess their association with breast cancer risk, five SNPs were genotyped in 1218 familial BRCA1/2-mutation negative breast cancer cases and 1509 controls (rs1804645, rs6094752, rs2230782, rs2076546, rs2229840).

Results

Through our resequencing effort, we identified 74 novel SNPs (30 in NCoR, 32 in SMRT, 10 in SRC-3, and 2 in SRC-1). Of these, 8 were found with minor allele frequency (MAF) >5% illustrating the large amount of genetic diversity yet to be discovered. The previously shown protective effect of rs2230782 in SRC-3 was strengthened (OR = 0.45 [0.21-0.98], p = 0.04). No significant associations were found with the other SNPs genotyped.

Conclusions

This data illustrates the importance of coregulators, especially SRC-3, in breast cancer development and suggests that more focused studies, including functional analyses, should be conducted.
Evaluation of single-nucleotide polymorphism imputation using random forests
Authors: Schwarz Daniel F , Szymczak Silke , Ziegler Andreas , König Inke R
Published: December 2009

Genome-wide association studies (GWAS) have helped to reveal genetic mechanisms of complex diseases. Although commonly used genotyping technology enables us to determine up to a million single-nucleotide polymorphisms (SNPs), causative variants are typically not genotyped directly. A favored approach to increase the power of genome-wide association studies is to impute the untyped SNPs using more complete genotype data of a reference population.

Random forests (RF) provides an internal method for replacing missing genotypes. A forest of classification trees is used to determine similarities of probands regarding their genotypes. These proximities are then used to impute genotypes of untyped SNPs.

We evaluated this approach using genotype data of the Framingham Heart Study provided as Problem 2 for Genetic Analysis Workshop 16 and the Caucasian HapMap samples as reference population. Our results indicate that RFs are faster but less accurate than alternative approaches for imputing untyped SNPs.
The adequacy of policy responses to the treatment needs of South Africans living with HIV (1999‐2008): a case study
Authors: Gow Jeff A
Published: December 2009

Introduction

South Africa has the largest HIV/AIDS epidemic of any country in the world.

Case description

National antiretroviral therapy (ART) policy is examined over the period of 1999 to 2008, which coincided with the government of President Thabo Mbeki and his Minister of Health, Dr Manto Tshabalala‐Msimang. The movement towards a national ART programme in South Africa was an ambitious undertaking, the likes of which had not been contemplated before in public health in Africa.

Discussion and evaluation

One million AIDS‐ill individuals were targeted to be enrolled in the ART programme by 2007/08. Fewer than 50% of eligible individuals were enrolled. This failure resulted from lack of political commitment and inadequate public health system capacity. The human and economic costs of this failure are large and sobering.

Conclusions

The total lost benefits of ART not reaching the people who need it are estimated at 3.8 million life years for the period, 2000 to 2005. The economic cost of those lost life years over this period has been estimated at more than US$15 billion.
Fast least-squares migration with a deblurring filter
Authors: Aoki Naoshi , Schuster Gerard T.
Published: December 2009

Least-squares migration (LSM) is a linearized waveform inversion for estimating a subsurface reflectivity model that, relative to conventional migration, improves spatial resolution of migration images. The cost, however, is high because LSM typically requires 10 or more iterations, which is at least 20 times more than the CPU cost of conventional migration. To alleviate this expense, we offer a deblurring filter that can be used in a regularization scheme or a preconditioning scheme to give acceptable LSM images with less than one-third the cost of the standard LSM method. Our results in applying deblurred LSM to synthetic data and field data support this claim. In particular, a Marmousi2 model test shows that the data residual for preconditioned deblurred LSM decreases rapidly in the first iteration, which is equivalent to 10 or more iterations of LSM. Empirical results suggest that regularized deblurred LSM after three iterations is equivalent to about 10 iterations of LSM. Applying deblurred LSM to 2D marine data gives a higher-resolution image compared to those from migration or LSM with three iterations. These results suggest that LSM combined with a deblurring filter allows LSM to be a fast, practical tool for improved imaging of complicated structures.
Prestack depth imaging of ocean-bottom node data
Authors: Alerini Mathias , Traub Bärbel , Ravaut Céline , Duveneck Eric
Published: December 2009

Ocean-bottom node acquisitions provide high-quality data but usually have large distances between the nodes because of cost. This makes the use of conventional processing difficult and has led to relatively little interest in such data for industrial purposes. We have considered a three-step workflow specifically designed for prestack depth imaging of P-waves recorded by ocean-bottom nodes. It consists of multiple attenuation, velocity model estimation, and prestack depth migration. Whereas multiple attenuation and tomography use data in the common-receiver domain, migration is performed in the common-angle domain. One of the main features is the handling of the sparse receiver geometry during velocity model estimation: the reciprocity of the PP-Green’s functions is used to obtain the required tomographic input using only the common-receiver gathers. The tomographic method also provides an estimate of the geologic dip, which is used to limit the migration operator. This provides migrated images free of migration smiles. The workflow contains no additional assumptions compared to those used to process ocean-bottom cable data. We validate the workflow on a 2D line extracted from a 3D real data set acquired in the North Sea. The results show that it is possible to use ocean-bottom data efficiently for prestack depth imaging.
Efficacy and Safety of Pazopanib in Patients With Metastatic Renal Cell Carcinoma
Authors: Hutson Thomas E. , Davis Ian D. , Machiels Jean-Pascal H. , De Souza Paul L. , Rottey Sylvie , Hong Bao-fa , Epstein Richard J. , Baker Katherine L. , McCann Lauren , Crofts Theresa , Pandite Lini , Figlin Robert A.
Published: December 2009

Purpose

Inactivation of the von Hippel-Lindau gene in clear-cell renal cell carcinomas (RCC) leads to overexpression of hypoxia inducible factor, a transcription factor regulating vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) gene expression. Pazopanib, an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor, and c-KIT, was evaluated in patients with RCC.

Patients and Methods

This phase II study was designed as a randomized discontinuation study but was revised to an open-label study on the recommendation of the data monitoring committee (based on week 12 response rate [RR] of 38% in the first 60 patients). The primary end point was changed from progressive disease rate at 16 weeks postrandomization to RR. Pazopanib 800 mg was administered orally once daily. Pazopanib 800 mg was administered orally once daily.

Results

The study enrolled 225 patients with metastatic RCC; 155 patients (69%) were treatment naïve, and 70 patients (31%) had received one prior cytokine- or bevacizumab-containing regimen. Overall RR was 35%; median duration of response was 68 weeks. Median progression-free survival (PFS) was 52 weeks. Eastern Cooperative Oncology Group performance status of 0 and time from diagnosis to treatment of more than 1 year were correlated with prolonged PFS. Pazopanib was generally well tolerated. The most common adverse events were diarrhea, fatigue, and hair depigmentation. The most common laboratory abnormalities were elevated AST and ALT.

Conclusion

Pazopanib demonstrated durable activity in patients with advanced RCC and was generally well tolerated in this population. These findings support the further development of pazopanib in advanced RCC.
Older Breast Cancer Survivors: Geriatric Assessment Domains Are Associated With Poor Tolerance of Treatment Adverse Effects and Predict Mortality Over 7 Years of Follow-Up
Authors: Clough-Gorr Kerri M. , Stuck Andreas E. , Thwin Soe Soe , Silliman Rebecca A.
Published: December 2009

Purpose

To evaluate geriatric assessment (GA) domains in relation to clinically important outcomes in older breast cancer survivors.

Methods

Six hundred sixty women diagnosed with primary breast cancer in four US geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island) were selected with disease stage I to IIIA, age ≥ 65 years at date of diagnosis, and permission from attending physician to contact. Data were collected over 7 years of follow-up from consenting patients' medical records, telephone interviews, physician questionnaires, and the National Death Index. Outcomes included self-reported treatment tolerance and all-cause mortality. Four GA domains were described by six individual measures, as follows: sociodemographic by adequate finances; clinical by Charlson comorbidity index (CCI) and body mass index; function by number of physical function limitations; and psychosocial by the five-item Mental Health Index (MHI5) and Medical Outcomes Study Social Support Survey (MOS-SSS). Associations were evaluated using t tests, χ2 tests, and regression analyses.

Results

In multivariable regression including age and stage, three measures from two domains (clinical and psychosocial) were associated with poor treatment tolerance; these were CCI ≥ 1 (odds ratio [OR] = 2.49; 95% CI, 1.18 to 5.25), MHI5 score less than 80 (OR = 2.36; 95% CI, 1.15 to 4.86), and MOS-SSS score less than 80 (OR = 3.32; 95% CI, 1.44 to 7.66). Four measures representing all four GA domains predicted mortality; these were inadequate finances (hazard ratio [HR] = 1.89; 95% CI, 1.24 to 2.88; CCI ≥ 1 (HR = 1.38; 95% CI, 1.01 to 1.88), functional limitation (HR = 1.40; 95% CI, 1.01 to 1.93), and MHI5 score less than 80 (HR = 1.34; 95% CI, 1.01 to 1.85). In addition, the proportion of women with these outcomes incrementally increased as the number of GA deficits increased.

Conclusion

This study provides longitudinal evidence that GA domains are associated with poor treatment tolerance and predict mortality at 7 years of follow-up, independent of age and stage of disease.
Impact of Environmental Tobacco Smoke on the Incidence of Mutations in Epidermal Growth Factor Receptor Gene in Never-Smoker Patients With Non–Small-Cell Lung Cancer
Authors: Lee Young Joo , Cho Byoung Chul , Jee Sun Ha , Moon Jin Wook , Kim Se Kyu , Chang Joon , Chung Kyung Young , Park In Kyu , Choi Sung Ho , Kim Joo-Hang
Published: December 2009

Purpose

Active tobacco smoking has been associated with the incidence of epidermal growth factor receptor (EGFR) mutations. However, the impact of environmental tobacco smoke (ETS) on EGFR mutations has been unknown. We investigated an association between ETS exposure and EGFR mutations in never smokers with non–small-cell lung cancer (NSCLC).

Patients and Methods

We enrolled 179 consecutive never smokers who were newly diagnosed with NSCLC. The history of ETS exposure was obtained with a standardized questionnaire that included exposure period, place, and duration. The nucleotide sequences of exons 18 to 21 on EGFR gene were determined using nested polymerase chain reaction amplification.

Results

The incidence of EGFR mutations was significantly lower in patients with ETS exposure than in those without (38.5% v 61.4%; P = .008). In a logistic regression model that adjusted for sex and histology, an adjusted odds ratio (AOR) for the risk of EGFR mutations with exposure to ETS was 0.40 (95% CI, 0.20 to 0.81; P = .011). In quartile groups based on total smoker-year, the AORs for the lowest- to highest-quartile groups were 0.59 (95% CI, 0.23 to 1.49), 0.50 (95% CI, 0.17 to 1.50), 0.48 (95% CI, 0.20 to 1.18), and 0.22 (95% CI, 0.08 to 0.62; Ptrend= .028). Among the types of ETS exposure, adulthood ETS and household ETS were significantly associated with the incidence of EGFR mutations. Patients with ETS exposure showed a lower response rate to EGFR tyrosine kinase inhibitors than did patients without ETS exposure (24.6% v 44.8%; P = .053).

Conclusion

ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.
History and the Challenge of Photography in Bertolt Brecht's Kriegsfibel
Authors: Imbrigotta Kristopher
Published: December 2009

With the onset and proliferation of today's twenty-four-hour mass media culture, war in particular has become—and will continue to be—very photogenic. But can we rely on what we see? What is missing from that message? Strictly speaking, Marxist thinkers and critics have been skeptical of images and their ability to faithfully convey the realities of class, power, and truth; and to a certain extent, Bertolt Brecht was no different. However, such a blanket statement does not fully capture the often tenuous working relationship that Brecht and photography share. This statement prompts many questions: Does photography uncover truth or cover up societal relations? How does Brecht employ photographs to expose contradictions? Can we continue to read contemporary images of war as Brecht sought to read/use them more than fifty years ago in his works? This essay will briefly outline how Brecht juxtaposed appropriated press photographs and poetic commentary to help us rethink our approach to history, war, and visual representation and will then argue for photography's continued critical relevance to our current relationship with and assessment of the causes and effects of global conflict.
Representations of Conflict
Authors: Gandolfo K. Luisa
Published: December 2009

Since 1948 the Palestine-Israel conflict has provided a source of inspiration for writers and photographers both within and outside the region. As the years of war have worn inexorably on, the changes wrought by events in the region have been rendered by Palestinian artists. This article focuses on the Palestinian art scene from 1948 onward, tracing the evolution of Palestinian art and symbols of war, resistance, and national identity in the works of artists such as Sliman Mansour and Naji Al-Ali. The article also assesses the representation of the female form and the significance of identity in artistic works during times of conflict.
Filming Resistance
Authors: el Houri Walid , Saber Dima
Published: December 2009

The article focuses on Hezbollah's filmed operations as key media texts in the group's discourse of resistance. In 1986 Hezbollah surprised the public with an innovation in their strategies of resistance: their fighters filmed one of their armed operations in the occupied southern Lebanon and broadcast it to the public. This video, followed by numerous others, had an impact on the growing popularity of the movement and, even more so, on the construction of their image in the minds of both their public and the Israeli one.

First broadcast by national media, these videos are now in online archives accessible to anyone at any time through Hezbollah's Internet sites. Stemming from Michel Foucault's and Edward Said's notions of power and knowledge, the article reads these videos as a strategy of resistance and as an attempt at self-representation that defies and inverts the prevalent relation of power and domination. The videos act as a metaphor of empowerment of a dominated self being presented as the “one who sees,” the “one who allows to see,” and the “one who is seen.” Thus they become what Daniel Dayan calls “monstration”: a reality that exists only through the way it is shown.
Imagining Militarism
Authors: Cohen Michael
Published: December 2009

In 1915 Art Young, the most important radical cartoonist of the Haymarket Generation, drew a simple image for The Masses of a gigantic man laden with weapons striding across the earth, captioned “Looking for Peace.” This image, appearing between the Ludlow massacre, the U.S. military intervention in the Mexican Revolution, and the growth of Preparedness campaigns before the U.S. entry into World War I, represents a new character in the visual culture of American popular radicalism: the figure of the Militarist. Far from being reductive or simplistic, this cartoon represents a complex critique of American militarism as it appeared to Young, Jack Reed, and the artists and intellectuals associated with The Masses, who rose in opposition to this violent new political enemy. Through a close reading of this image and its place in the visual culture of early-twentieth-century radicalism, I argue that by combining the corpulent physicality of J. P. Morgan the Plutocrat, the aggressive gesture of the Rooseveltian Imperialist, and the costume of Uncle Sam, Young's Militarist mapped the emergent political economy behind American militarism. This gave a visual, allegorical, and highly influential presence to the anticapitalist Left's newest and greatest enemy in the early twentieth century.