bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily Oral Everolimus Activity in Patients With Metastatic Pancreatic Neuroendocrine Tumors After Failure of Cytotoxic Chemotherapy: A Phase II Trial
Authors: Yao James C. , Lombard-Bohas Catherine , Baudin Eric , Kvols Larry K. , Rougier Philippe , Ruszniewski Philippe , Hoosen Sakina , St. Peter Jessica , Haas Tomas , Lebwohl David , Van Cutsem Eric , Kulke Matthew H. , Hobday Timothy J. , O'Dorisio Thomas M. , Shah Manisha H. , Cadiot Guillaume , Luppi Gabriele , Posey James A. , Wiedenmann Bertram
Published: November 2009

Purpose

No established treatment exists for pancreatic neuroendocrine tumor (NET) progression after failure of chemotherapy. Everolimus (RAD001), an oral inhibitor of mammalian target of rapamycin, in combination with octreotide has demonstrated encouraging antitumor activity in patients with NETs.

Patients and Methods

This open-label, phase II study assessed the clinical activity of everolimus in patients with metastatic pancreatic NETs who experienced progression on or after chemotherapy. Patients were stratified by prior octreotide therapy (stratum 1: everolimus 10 mg/d, n = 115; stratum 2: everolimus 10 mg/d plus octreotide long-acting release [LAR], n = 45). Tumor assessments (using Response Evaluation Criteria in Solid Tumors) were performed every 3 months. Chromogranin A (CgA) and neuron-specific enolase (NSE) were assessed monthly if elevated at baseline. Trough concentrations of everolimus and octreotide were assessed.

Results

By central radiology review, in stratum 1, there were 11 partial responses (9.6%), 78 patients (67.8%) with stable disease (SD), and 16 patients (13.9%) with progressive disease; median progression-free survival (PFS) was 9.7 months. In stratum 2, there were two partial responses (4.4%), 36 patients (80%) with SD, and no patients with progressive disease; median PFS was 16.7 months. Patients with an early CgA or NSE response had a longer PFS compared with patients without an early response. Coadministration of octreotide LAR and everolimus did not impact exposure to either drug. Most adverse events were mild to moderate and were consistent with those previously seen with everolimus.

Conclusion

Daily everolimus, with or without concomitant octreotide LAR, demonstrates antitumor activity as measured by objective response rate and PFS and is well tolerated in patients with advanced pancreatic NETs after failure of prior systemic chemotherapy.
Cytidine Deaminase Residual Activity in Serum Is a Predictive Marker of Early Severe Toxicities in Adults After Gemcitabine-Based Chemotherapies
Authors: Ciccolini Joseph , Dahan Laetitia , André Nicolas , Evrard Alexandre , Duluc Muriel , Blesius Aurore , Yang Chenguang , Giacometti Sarah , Brunet Caroline , Raynal Caroline , Ortiz Adrien , Frances Nicolas , Iliadis Athanassios , Duffaud Florence , Seitz Jean-François , Mercier Cédric
Published: November 2009

Purpose

Anticipating toxicities with gemcitabine is an ongoing story, and deregulation in cytidine deaminase (CDA) could be associated with increased risk of developing early severe toxicities on drug exposure.

Patients and Methods

A simple test to evaluate CDA phenotypic status was first validated in an animal model investigating relationships between CDA activity and gemcitabine-related toxicities. Next, relevance of this test as a marker for toxicities was retrospectively tested in a first subset of 64 adult patients treated with gemcitabine alone, then it was tested in a larger group of 130 patients who received gemcitabine either alone or combined with other drugs and in 20 children. Additionally, search for the 435 T>C, 208 G>A and 79 A>C mutations on the CDA gene was performed.

Results

In mice, CDA deficiency impacted on gemcitabine pharmacokinetics and had subsequent lethal toxicities. In human, 12% of adult patients experienced early severe toxicities after gemcitabine administration. A significant difference in CDA activities was observed between patients with and without toxicities (1.2 ± 0.8 U/mg v 4 ± 2.6 U/mg; P < .01). Conversely, no genotype-to-phenotype relationships were found. Of note, the patients who displayed particularly reduced CDA activity all experienced strong toxicities. Gemcitabine was well tolerated in children, and no CDA deficiency was evidenced.

Conclusion

Our data suggest that CDA functional testing could be a simple and easy marker to discriminate adult patients at risk of developing severe toxicities with gemcitabine. Particularly, this study demonstrates that CDA deficiency, found in 7% of adult patients, is associated with a maximum risk of developing early severe toxicities with gemcitabine.
Carboplatin and Paclitaxel in Combination With Either Vorinostat or Placebo for First-Line Therapy of Advanced Non–Small-Cell Lung Cancer
Authors: Ramalingam Suresh S. , Maitland Michael L. , Frankel Paul , Argiris Athanassios E. , Koczywas Marianna , Gitlitz Barbara , Thomas Sachdev , Espinoza-Delgado Igor , Vokes Everett E. , Gandara David R. , Belani Chandra P.
Published: November 2009

Purpose

Vorinostat, a histone deacetylase inhibitor, exerts anticancer effects by both histone and nonhistone–mediated mechanisms. It also enhances the anticancer effects of platinum compounds and taxanes in non–small-cell lung cancer (NSCLC) cell lines. This phase II randomized, double-blinded, placebo-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxel in patients with advanced-stage NSCLC.

Patients and Methods

Patients with previously untreated stage IIIB (ie, wet) or IV NSCLC were randomly assigned (2:1) to carboplatin (area under the curve, 6 mg/mL × min) and paclitaxel (200 mg/m2 day 3) with either vorinostat (400 mg by mouth daily) or placebo. Vorinostat or placebo was given on days 1 through 14 of each 3-week cycle to a maximum of six cycles. The primary end point was comparison of the response rate.

Results

Ninety-four patients initiated protocol therapy. Baseline patient characteristics were similar between the two arms. The median number of cycles was four for both treatment arms. The confirmed response rate was 34% with vorinostat versus 12.5% with placebo (P = .02). There was a trend toward improvement in median progression-free survival (6.0 months v 4.1 months; P = .48) and overall survival (13.0 months v 9.7 months; P = .17) in the vorinostat arm. Grade 4 platelet toxicity was more common with vorinostat (18% v 3%; P < .05). Nausea, emesis, fatigue, dehydration, and hyponatremia also were more frequent with vorinostat.

Conclusion

Vorinostat enhances the efficacy of carboplatin and paclitaxel in patients with advanced NSCLC. HDAC inhibition is a promising therapeutic strategy for treatment of NSCLC.
Immunoglobulin G Fc Receptor FcγRIIIa 158 V/F Polymorphism Correlates With Rituximab-Induced Neutropenia After Autologous Transplantation in Patients With Non-Hodgkin's Lymphoma
Authors: Weng Wen-Kai , Negrin Robert S. , Lavori Philip , Horning Sandra J.
Published: November 2009

Purpose

Rituximab has been given after autologous hematopoietic cell transplantation for recurrent or refractory B-cell lymphoma with the goal of eradicating minimal residual disease. Our previous report showed that administration of two courses of rituximab after transplantation is feasible, with encouraging clinical outcomes after a short follow-up. However, neutropenia after the first or second post-transplantation rituximab treatment occurred in 52% of patients. We previously reported that polymorphisms of two immunoglobulin G Fc receptors predict rituximab response, presumably because of their role in antibody-dependent cellular cytotoxicity. In the current report, we determine whether FcγR polymorphisms are correlated with clinical outcomes in 33 patients with B-cell non-Hodgkin's lymphoma who received post-transplantation rituximab.

Patients and Methods

Genomic DNA was used for FcγRIIIa V/F or the FcγRIIa H/R genotyping. The FcγR polymorphisms were then correlated with the incidence of rituximab-induced neutropenia, event-free survival (EFS), and overall survival (OS).

Results

The FcγRIIIa 158 V allele dose was correlated with a higher incidence of rituximab-induced neutropenia. The odds of neutropenia after the first or second post-transplantation rituximab increased three-fold with each V allele (robust z = 2.08, P = .038). The FcγRIIa polymorphism had no impact on rituximab-induced neutropenia. We did not observe a correlation of either FcγRIIIa or FcγRIIa polymorphism with EFS or OS.

Conclusion

The high affinity FcγRIIIa 158 V allele is associated with rituximab-induced neutropenia after autologous transplantation. This is a potential tool to identify a high-risk population for developing neutropenia after antibody therapy.
The Logic of Left Alone: The Pioneers and the Conditions of U.S. Privacy
Authors: Insko Jeffrey
Published: November 2009

A familiar refrain in U.S. history, “leave me alone” has long been the preferred locution with which one affirms one's right to privacy. Insko's essay investigates a conceptual incoherence at the heart of the various, incompatible definitions and applications of the right to privacy in U.S. history by describing a persistent and paradoxical U.S. cultural logic: the logic of left alone. The essay argues that James Fenimore Cooper's 1823 novel The Pioneers contributes to an inchoate discourse of privacy rights, the contours of which continue to define present-day understandings of the relations between privacy and personhood, as inscribed by the recent Supreme Court decision Lawrence v. Texas and the military's “don't ask, don't tell” policy. Rather than tracking the curve along which U.S. notions of privacy transformed during the antebellum period and after, Insko's essay explores the extent to which the often-contradictory coordinates that delineate this curve animate modern philosophical and legal conceptions of privacy in the same ways they animate The Pioneers—a novel that presciently narrates the fraught conditions of the right to privacy in U.S. history.
Red Cars with Red Lights and Red Drivers: Color, Crane, and Qualia
Authors: Gaskill Nicholas
Published: November 2009

Gaskill's essay situates Stephen Crane's well-known fascination with color within the historical and philosophical contexts of the late-nineteenth century. The invention of bright synthetic dyes and pigments and their applications within emerging advertising culture combined with theories of color sensation and perception offered by empirical psychologists to produce new opportunities for and understandings of color experience. Color—increasingly puzzled over in the abstract, apart from any instantiations within objects—came to be regarded as an affective force with direct and controllable effects on human minds and bodies.

In stories such as “The Blue Hotel” and “The Broken-Down Van” and in the novels The Red Badge of Courage and The Third Violet, Crane draws from and contributes to these experiments with abstract or “pure” color. He uses color to explore the networks of sensation, perception, and language that constitute experience, and he develops a literary style that lifts the feeling of colors from their visual appearances in order to bring his language into contact with the sensory and affective force of color. In this regard, Crane's color techniques relate to late-nineteenth-century philosophical discussions of qualia. This essay elaborates on these themes and practices—touching on Goethe's Theory of Colours, Art Nouveau, the work of Charles Sanders Peirce, and chromotherapy—to offer an account of Crane's colors that revises critical accounts of his “impressionism” and that attends to historical understandings of the character of experience.
Synthesis of Metal-doped LiFePO4 from Nickel Laterite Lixivium
Authors: Li Ling-jun , Li Xin-hai , Wang Zhi-xing , Wu Ling , Zheng Jun-chao , Yan Hao , Guo Hua-jun
Published: November 2009

Nickel laterite lixivium is purified by fast phosphate coprecipitation. ICP analysis confirms that Ni, Co, Mn recovery rates are 88.83, 92.66, 93.48%, respectively, and all iron is removed as FePO4·xH2O precursor with trace Al, Mg, Ni, and Mn elements. To evaluate the structure and electrochemical performance of FePO4·xH2O, metal-doped LiFePO4 is prepared from the as-prepared precursor. It is noted that the metal-doped LiFePO4 exhibits well-crystallized structure, homogeneous distribution, and excellent electrochemical properties.
Thiofluorination of Carbon–Carbon Multiple Bonds Using Electrochemically Generated ArS(ArSSAr)+BF4−
Authors: Fujie Shunsuke , Matsumoto Kouichi , Suga Seiji , Yoshida Jun-ichi
Published: November 2009

The reaction of alkenes and alkynes with ArS(ArSSAr)+BF4−, which was generated and accumulated by the low-temperature anodic oxidation of ArSSAr in Bu4NBF4/CH2Cl2, led to the addition of an ArS group and fluoride across the carbon–carbon multiple bond to give thiofluorinated compounds in good yields.
A Luminescent Oligo(p-phenylenevinylene) Wrapped with Amylose
Authors: Kato Nobu , Sanji Takanobu , Tanaka Masato
Published: November 2009

When wrapped with amylose, oligo(p-phenylenevinylene) exists in a state that is isolated from the external environment, thereby hampering the π–π interactions and displaying an intense blue emission arising from the chiral conformation of the main chain.
Synthesis of Noria-like Macrocycles Containing Alkoxy Groups based on a Dynamic Covalent Chemistry (DCC) System by the A2 + B4 Condensation
Authors: Niina Nobumitsu , Kudo Hiroto , Nishikubo Tadatomi
Published: November 2009

We succeeded in the synthesis of new noria-like macrocycles by condensation of 3-alkoxyphenol as A2 type monomers, and pentanedial as B4 type monomer. These condensation reactions were performed using several acids as catalysts in ethanol and CHCl3. It was found that these reactions proceeded by DCC to afford soluble polymers, oligomers, and noria-like ladder macrocycles. As the result, the selective synthesis of the targeted noria-like macrocycles was achieved successfully in high yields.
A strategy to analyze the phenotypic consequences of inhibiting the association of an RNA-binding protein with a specific RNA
Authors: Cibois Marie , Gautier-Courteille Carole , Vallée Audrey , Paillard Luc
Published: November 2009

Targeted inactivations of RNA-binding proteins (RNA-BPs) can lead to huge phenotypical defects. These defects are due to the deregulation of certain mRNAs. However, we generally do not know, among the hundreds of mRNAs that are normally controlled by one RNA-BP, which are responsible for the observed phenotypes. Here, we designed an antisense oligonucleotide (“target protector”) that masks the binding site of the RNA-BP CUG-binding protein 1 (CUGBP1) on the mRNA Suppressor of Hairless [Su(H)] that encodes a key player of Notch signaling. We showed that injecting this oligonucleotide into Xenopus embryos specifically inhibited the binding of CUGBP1 to the mRNA. This caused the derepression of Su(H) mRNA, the overexpression of Su(H) protein, and a phenotypic defect, loss of somitic segmentation, similar to that caused by a knockdown of CUGBP1. To demonstrate a causal relationship between Su(H) derepression and the segmentation defects, a rescue experiment was designed. Embryonic development was restored when the translation of Su(H) mRNA was re-repressed and the level of Su(H) protein was reduced to a normal level. This “target protector and rescue assay” demonstrates that the phenotypic defects associated with CUGBP1 inactivation in Xenopus are essentially due to the deregulation of Su(H) mRNA. Similar approaches may be largely used to uncover the links between the phenotype caused by the inactivation of an RNA-BP and the identity of the RNAs associated with that protein.
What is ‘translation’?
Authors: Freeman Richard
Published: November 2009

What is ‘translation’, and how might it help us think differently about knowledge transfer and exchange? The purpose of this article is to set out, for policy makers and practitioners, the theoretical and conceptual resources that translation holds and seems to represent. It begins by recasting research, policy and practice themselves as instances of translation. It explores understandings of translation in literature and linguistics and in the sociology of science and technology, developing them in respect of a brief case study of the seminal women’s health text, Our bodies, ourselves. In concluding, it picks up key themes of uncertainty, practice and complexity.
(De)constructing a policy ‘failure’: housing stock transfer in Glasgow
Authors: Kearns Ade , Lawson Louise
Published: November 2009

The most significant housing stock transfer in the UK took place in Glasgow in 2003. It has been widely and repeatedly depicted as a policy ‘failure’, by both journalists and informed critics. This article evaluates the specific claims of failure by looking at developments to date and the available evidence. It uses an available theoretical framework to consider how such judgements have been arrived at, revealing the biases contained therein. The label of ‘failure’ is rejected, but policy deficiencies are identified; again, a theoretical framework is used to relate these weaknesses to the nature of the politics involved in the formation and oversight of the policy.
Promoting intergenerational programmes: where is the evidence to inform policy and practice?
Authors: Statham Elaine
Published: November 2009

UK government and non-governmental organisations are promoting the use of intergenerational programmes in England and Wales to improve community cohesion. However, much thought needs to be given to designing programmes, and intergenerational projects stand an increased chance of succeeding if they draw on previous successes and failures. This will only be possible if the dearth of readily accessible and practical information needed by practitioners is rectified. In this article, recommendations are made on what needs to be done to progress intergenerational programmes and relations, achieve successful outcomes, and avoid unintended consequences such as reinforcing negative, ageist stereotypes and exacerbating already fragile intergenerational relationships.
Assessment of regional changes in skeletal metabolism following 3 and 18 months of teriparatide treatment
Authors: Moore Amelia EB , Blake Glen M , Taylor Kathleen A , Rana Asad E , Wong Mayme , Chen Peiqi , Fogelman Ignac
Published: November 2009

Teriparatide (TPTD) increases skeletal mass, bone turnover markers, and bone strength, but in vivo effects at individual skeletal sites have not been characterized. Quantitative radionuclide imaging studies reflect bone blood flow and osteoblast activity to assess regional changes in bone metabolism. Changes in bone plasma clearance using technetium-99m methylene diphosphonate (99mTc-MDP) were quantified and correlated with changes in bone turnover markers in 10 postmenopausal women with osteoporosis. Subjects underwent bone scintigraphy at baseline and 3 and 18 months after initiating TPTD 20 µg/day subcutaneously. Subjects were injected with 600 MBq 99mTc-MDP, and whole-body bone scan images were acquired at 10 minutes and 1, 2, 3, and 4 hours. Multiple blood samples were taken between 5 minutes and 4 hours after treatment, and free 99mTc-MDP was measured using ultrafiltration. The Patlak plot method was used to evaluate whole-skeleton 99mTc-MDP plasma clearance (Kbone) and derive regional bone clearance for the calvarium, mandible, spine, pelvis, and upper and lower extremities using gamma camera counts. Bone turnover markers were measured at baseline and 3, 12, and 18 months. Median increases from baseline in whole-skeleton Kbone were 22.3% (p = .004) and 33.7% (p = .002) at 3 and 18 months, respectively. Regional Kbone values were increased significantly in all six subregions at 3 months and in all subregions except the pelvis at 18 months. Bone markers were increased significantly from baseline at 3 and 18 months and correlated significantly with whole-skeleton Kbone. This is the first study showing a direct metabolic effect of TPTD at different skeletal sites in vivo, as measured by tracer kinetics. © 2010 American Society for Bone and Mineral Research
ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation
Authors: Dinther Maarten van , Visser Nils , de Gorter David JJ , Doorn Joyce , Goumans Marie-José , de Boer Jan , ten Dijke Peter
Published: November 2009

Fibrodysplasia ossificans progressiva (FOP) is a rare disabling disease characterized by heterotopic ossification for which there is currently no treatment available. FOP has been linked recently to a heterozygous R206H mutation in the bone morphogenetic protein (BMP) type I receptor activin receptor–like kinase 2 (ALK2). Expression of the mutant ALK2-R206H receptor (FOP-ALK2) results in increased phosphorylation of the downstream Smad1 effector proteins and elevated basal BMP-dependent transcriptional reporter activity, indicating that FOP-ALK2 is constitutively active. FOP-ALK2-induced transcriptional activity could be blocked by overexpressing either of the inhibitory Smads, Smad6 or -7, or by treatment with the pharmacological BMP type I receptor inhibitor dorsomorphin. However, in contrast to wild-type ALK2, FOP-ALK2 is not inhibited by the negative regulator FKBP12. Mesenchymal cells expressing the FOP-ALK2 receptor are more sensitive to undergoing BMP-induced osteoblast differentiation and mineralization. In vivo bone formation was assessed by loading human mesenchymal stem cells (hMSCs) expressing the ALK2-R206H receptor onto calcium phosphate scaffolds and implantation in nude mice. Compared with control cells FOP-ALK2-expressing cells induced increased bone formation. Taken together, the R206H mutation in ALK2 confers constitutive activity to the mutant receptor, sensitizes mesenchymal cells to BMP-induced osteoblast differentiation, and stimulates new bone formation. We have generated an animal model that can be used as a stepping stone for preclinical studies aimed at inhibiting the heterotopic ossification characteristic of FOP. © 2010 American Society for Bone and Mineral Research
Long-term leisure-time physical activity has a positive effect on bone mass gain in girls
Authors: Völgyi Eszter , Lyytikäinen Arja , Tylavsky Frances A , Nicholson Patrick HF , Suominen Harri , Alén Markku , Cheng Sulin
Published: November 2009

The purpose of this 7-year prospective longitudinal study was to examine whether the level and consistency of leisure-time physical activity (LTPA) during adolescence affected the bone mineral content (BMC) and bone mineral density (BMD) attained at early adulthood. The study subjects were 202 Finnish girls who were 10 to 13 years of age at baseline. Bone area (BA), BMC, and BMD of the total body (TB), total femur (TF), and lumbar spine (L2–L4) were assessed by dual-energy X-ray absorptiometry (DXA). Scores of LTPA were obtained by questionnaire. Girls were divided into four groups: consistently low physical activity (GLL), consistently high (GHH), and changed from low to high (GLH) and from high to low (GHL) during 7 years of follow-up. At baseline, no differences were found in BA, BMC, and BMD among the groups in any of the bone sites. Compared with the GLL group, the GHH group had higher BMC (11.7% in the TF, p < .05) and BMD at the TB (4.5%) and the TF (12.2%, all p < .05) at age 18. Those in the GLH group also had higher a BMC at each site (8.5% to 9.4%, p < .05) and a higher BMD in the TB (5.4%) and the TF (8.9%) than that of GLL (all p < 0.05) at the age 18. Our results suggest that long-term leisure-time physical activity has a positive effect on bone mass gain of multiple bone sites in girls during the transition from prepuberty to early adulthood. In addition, girls whose physical activity increases during adolescence also benefit from bone mass gain. © 2010 American Society for Bone and Mineral Research
The Nuclear Component of a Cytonuclear Hybrid Incompatibility in Mimulus Maps to a Cluster of Pentatricopeptide Repeat Genes
Authors: Barr Camille M , Fishman Lila
Published: November 2009

Characterizing the genetic and molecular basis of hybrid incompatibilities is a first step toward understanding their evolutionary origins. We fine mapped the nuclear restorer (Rf) of cytoplasm-dependent anther sterility in Mimulus hybrids by identifying and targeting regions of the Mimulus guttatus genome containing large numbers of candidate pentatricopeptide repeat genes (PPRs). The single Mendelian locus Rf was first isolated to a 1.3-cM region on linkage group 7 that spans the genome's largest cluster of PPRs, then split into two tightly linked loci (Rf1 and Rf2) by <10 recombination events in a large (N = 6153) fine-mapping population. Progeny testing of fertile recombinants demonstrated that a dominant M. guttatus allele at each Rf locus was sufficient to restore fertility. Each Rf locus spans a physical region containing numerous PPRs with high homology to each other, suggesting recent tandem duplication or transposition. Furthermore, these PPRs have higher homology to restorers in distantly related taxa (petunia and rice) than to PPRs elsewhere in the Mimulus genome. These results suggest that the cytoplasmic male sterility (CMS)–PPR interaction is highly conserved across flowering plants. In addition, given our theoretical understanding of cytonuclear coevolution, the finding that hybrid CMS results from interactions between a chimeric mitochondrial transcript that is modified by Rf loci identified as PPRs is consistent with a history of selfish mitochondrial evolution and compensatory nuclear coevolution within M. guttatus.
ERECT PANICLE2 Encodes a Novel Protein That Regulates Panicle Erectness in Indica Rice
Authors: Zhu Keming , Tang Ding , Yan Changjie , Chi Zhengchang , Yu Hengxiu , Chen Jianmin , Liang Jiansheng , Gu Minghong , Cheng Zhukuan
Published: November 2009

Rice (Oryza sativa L.) inflorescence (panicle) architecture is an important agronomic trait for rice breeding. A number of high-yielding japonica rice strains, characterized by an erect panicle (EP) of their architecture, have been released as commercial varieties in China. But no EP-type indica varieties are released so far. Here, we identified two allelic erect-panicle mutants in indica rice, erect panicle2-1 (ep2-1) and erect panicle2-2 (ep2-2), exhibiting the characteristic erect panicle phenotype. Both mutants were derived from spontaneous mutation. We cloned the EP2 gene by way of a map-based cloning strategy, and a transgenic complementation test rescued the phenotype of ep2-1. Anatomical investigations revealed that the ep2 mutants have more vascular bundles and a thicker stem than that of wild-type plants, explaining the panicle erectness phenotype in ep2 mutants. It was shown that EP2 was specifically expressed in the vascular bundles of internodes by GUS staining and RT–PCR. EP2 encodes a novel plant-specific protein, which localizes to the endoplasmic reticulum with unknown biochemical function. In addition, EP2 also regulates other panicle characteristics, such as panicle length and grain size, but grain number per panicle shows little change, indicating that the mutation of the ep2 gene could be applied in EP-type indica rice breeding.
Proteasomal Degradation of Rpn4 in Saccharomyces cerevisiae Is Critical for Cell Viability Under Stressed Conditions
Authors: Wang Xiaogang , Xu Haiming , Ha Seung-Wook , Ju Donghong , Xie Youming
Published: November 2009

The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback loop in which the transcription factor Rpn4 induces the proteasome genes and is rapidly degraded by the assembled proteasome. In addition to the proteasome genes, Rpn4 regulates numerous other genes involved in a wide range of cellular pathways. Therefore, the Rpn4–proteasome negative feedback circuit not only controls proteasome abundance, but also gauges the expression of other Rpn4 target genes. Our previous work has shown that Rpn4-induced gene expression is critical for cell viability under stressed conditions. Here we investigate whether proteasomal degradation of Rpn4 is also important for cell survival in response to stress. To this end, we generate a stabilized Rpn4 mutant (Rpn4*) that retains its transcription activity. We find that expression of Rpn4* severely reduces cell viability in response to various genotoxic and proteotoxic agents. This detrimental effect can be eliminated by a point mutation that abolishes the transcription activity of Rpn4*, suggesting that overexpression of some Rpn4 target genes weakens the cell's ability to cope with stress. Moreover, we demonstrate that inhibition of Rpn4 degradation causes synthetic growth defects when combined with proteasome impairment resulting from mutation of a proteasome gene or accumulation of misfolded endoplasmic reticulum membrane proteins. Rpn4 thus represents an important stress-responsive mediator whose degradation as well as availability are critical for cell survival under stressed conditions.
Relative Impact of Influenza and Respiratory Syncytial Virus in Young Children
Authors: Bourgeois Florence T. , Valim Clarissa , McAdam Alexander J. , Mandl Kenneth D.
Published: November 2009

OBJECTIVE: We measured the relative impact of influenza and respiratory syncytial virus (RSV) infections in young children in terms of emergency department (ED) visits, clinical care requirements, and overall resource use.

METHODS: Patients who were aged ≤7 years and treated in the ED of a tertiary care pediatric hospital for an acute respiratory infection were enrolled during 2 winter seasons between 2003 and 2005. We quantified health care resource use for children with influenza or RSV infections, and extrapolated results to estimate the national resource use associated with influenza and RSV infections.

RESULTS: Nationally, an estimated 10.2 ED visits per 1000 children were attributable to influenza and 21.5 visits per 1000 to RSV. Children who were aged 0 to 23 months and infected with RSV had the highest rate of ED visits with 64.4 visits per 1000 children. Significantly more children required hospitalization as a result of an RSV infection compared with influenza, with national hospitalization rates of 8.5 and 1.4 per 1000 children, respectively. The total number of workdays missed yearly by caregivers of children who required ED care was 246965 days for influenza infections and 716404 days for RSV infections.

CONCLUSION: For young children, RSV is associated with higher rates of ED visits, hospitalization, and caregiver resource use than is influenza. Our results provide data on the large number of children who receive outpatient care for influenza and RSV illnesses and serve to inform analyses of prevention programs and treatments for both influenza and RSV disease.
Booster Vaccinations: Can Immunologic Memory Outpace Disease Pathogenesis?
Authors: Pichichero Michael E.
Published: November 2009

Almost all current vaccines work by the induction of antibodies in serum or on the mucosa to block adherence of pathogens to epithelial cells or interfere with microbial invasion of the bloodstream. However, antibody levels usually decline after vaccination to undetectable amounts if further vaccination does not occur. Persistence of vaccine-induced antibodies usually goes well beyond the time when they should have decayed to undetectable levels because of ongoing “natural” boosting or other immunologic mechanisms. The production of memory B and T cells is of clear importance, but the likelihood that a memory response will be fast enough in the absence of a protective circulating antibody level likely depends on the pace of pathogenesis of a specific organism. This concept is discussed with regard to Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis; hepatitis A and B; diphtheria, tetanus, and pertussis; polio, measles, mumps, rubella, and varicella; rotavirus; and human papilloma virus. With infectious diseases for which the pace of pathogenesis is less rapid, some individuals will contract infection before the memory response is fully activated and implemented. With infectious diseases for which the pace of pathogenesis is slow, immune memory should be sufficient to prevent disease.
Spatial Accessibility to Providers and Vaccination Compliance Among Children With Medicaid
Authors: Fu Linda Y. , Cowan Nuala , McLaren Rosie , Engstrom Ryan , Teach Stephen J.
Published: November 2009

OBJECTIVE: We examined the relationship between spatial accessibility to pediatric immunization providers and vaccination compliance in a low-income, urban population of children.

METHODS: In 2007, we accessed the Washington, DC, Immunization Information System (IIS) to collect data on the immunization statuses and residential addresses of children who were aged 19 to 35 months and had Medicaid insurance. In addition, we calculated each child's spatial accessibility to pediatric vaccination providers by assessing the provider-to-population ratio at each residential address. Spatial accessibility was divided into tertiles (low, medium, and high) of access. The relationship between spatial accessibility to providers and vaccination compliance was examined by using logistic regression analysis adjusting for age, type of vaccination provider, and enrollment in child care status.

RESULTS: Overall for our cohort of 4195 children, 80.5% of the children were up-to-date with vaccinations. Vaccination coverage ranged from 61.6% to 100% (median: 79.2%) among different neighborhoods. Having the highest level of access to pediatric vaccination providers was associated with 36% higher odds of being up-to-date as compared with having the lowest level of access. The middle tertile of access was associated with 25% higher odds of being up-to-date.

CONCLUSIONS: Within our low-income, urban population, children with higher spatial accessibility to pediatric vaccination providers were more likely to be up-to-date with vaccinations. This association may guide future studies and efforts to ensure adequate immunization coverage for children regardless of where they live.
Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder
Authors: Froehlich Tanya E. , Lanphear Bruce P. , Auinger Peggy , Hornung Richard , Epstein Jeffery N. , Braun Joe , Kahn Robert S.
Published: November 2009

OBJECTIVE: The study objective was to determine the independent and joint associations of prenatal tobacco and childhood lead exposures with attention-deficit/hyperactivity disorder (ADHD), as defined by current diagnostic criteria, in a national sample of US children.

METHODS: Data are from the 2001–2004 National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the US population. Participants were 8 to 15 years of age (N = 2588). Prenatal tobacco exposure was measured by report of maternal cigarette use during pregnancy. Lead exposure was assessed by using current blood lead levels. The Diagnostic Interview Schedule for Children was used to ascertain the presence of ADHD in the past year, on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.

RESULTS: A total of 8.7% (95% confidence interval [CI]: 7.3%–10.1%) of children met criteria for ADHD. Prenatal tobacco exposure (adjusted odds ratio [aOR]: 2.4 [95% CI: 1.5–3.7]) and higher current blood lead concentrations (aOR for third versus first tertile: 2.3 [95% CI: 1.5–3.8]) were independently associated with ADHD. Compared with children with neither exposure, children with both exposures (prenatal tobacco exposure and third-tertile lead levels) had an even greater risk of ADHD (aOR: 8.1 [95% CI: 3.5–18.7]) than would be expected if the independent risks were multiplied (tobacco-lead exposure interaction term, P < .001).

CONCLUSIONS: Prenatal tobacco and childhood lead exposures are associated with ADHD in US children, especially among those with both exposures. Reduction of these common toxicant exposures may be an important avenue for ADHD prevention.
Preschool-Aged Children's Television Viewing in Child Care Settings
Authors: Christakis Dimitri A. , Garrison Michelle M.
Published: November 2009

OBJECTIVE: The goal was to quantify television viewing in day care settings and to investigate the characteristics of programs that predict viewing.

METHODS: A telephone survey of licensed child care programs in Michigan, Washington, Florida, and Massachusetts was performed. The frequency and quantity of television viewing for infants, toddlers, and preschool-aged children were assessed.

RESULTS: With the exception of infants, children in home-based child care programs were exposed to significantly more television on an average day than were children in center-based programs (infants: 0.2 vs 0 hours; toddlers: 1.6 vs 0.1 hours; preschool-aged children: 2.4 vs 0.4 hours). In a regression analysis of daily television time for preschool-aged children in child care, center-based programs were found to have an average of 1.84 fewer hours of television each day, controlling for the other covariates. Significant effect modification was found, in that the impact of home-based versus center-based child care programs differed somewhat depending on educational levels for staff members; having a 2- or 4-year college degree was associated with 1.41 fewer hours of television per day in home-based programs, but no impact of staff education on television use was observed in center-based programs.

CONCLUSIONS: For many children, previous estimates of screen time significantly underestimated actual amounts. Pediatricians should council parents to minimize screen time in child care settings.
Transcendence and Religion
Authors: Borg Meerten B. ter
Published: November 2009

This essay deals with the relationship between religion, both implicit and explicit, and transcendence. The starting point is Thomas Luckmann’s idea that man is a religious animal. After all, it is necessary for human beings to transcend their biological habitus in order to survive. It is suggested that transcendence is a necessary, rather than a sufficient precondition for religion.
Three Types of Liquid Religion
Authors: Groot Kees de
Published: November 2009

This article explores ways to think of religion using Zygmunt Bauman’s concept of liquid modernity. The concept of liquid religion opens up perspectives for both “new” and “old” social forms of religion that seem to flourish within a liquid milieu. Attention is also drawn to three types of relationship between solid and liquid religion. The first type consists of liquid phenomena in the religious sphere: religious events, small communities, global religious networks and virtual communities. The second type consists of phenomena on the boundaries between the religious and the secular sphere, such as religious services in a hospital or a prison. The third type consists of meetings and collective activities outside the religious sphere, such as those in the political and cultural spheres, which nonetheless have important religious qualities. This typology is used to make general observations on the basis of empirical research, mainly conducted in the Netherlands.
Patterns of Secularization and Religious Rationalization in Emile Durkheim and Max Weber
Authors: Goldstein Warren S.
Published: November 2009

Emile Durkheim’s and Max Weber’s sociologies of religion contain three different patterns of secularization and religious rationalization: the unilinear, the dialectical, and the nonlinear (which includes the paradoxical). Based on an analysis of Durkheim’s and Weber’s writings on religion, this paper argues that the process of religious rationalization and secularization is not always linear but can also take place in a dialectical or paradoxical manner. Whereas in the unilinear and dialectical theories of religious rationalization and secularization there is a progressive development, in the nonlinear or paradoxical theory, development is arrested. While the unilinear and dialectical theories are associated with the Occidental development to modernity, the paradoxical nature of theoretical religious rationalization was characteristic of the “arrested” development of the Orient, while the paradoxical aspects of secularization are associated with unresolved contradictions of modernity (the postmodern).
The Religious Dimensions of Compulsive Buying
Authors: Ayra Rina
Published: November 2009

This paper examines the implicit religiosity of compulsive buying. Much of the extant literature on the subject focuses on biological and/or psychological factors. I argue that the cycle of behaviour in compulsive buying, which oscillates between euphoria and depression, can be paralleled with Durkheim’s exposition of collective effervescence. In my paper I argue that many of the behaviours expressed in the cycles of compulsive buying can be described as religious, and that the sense of fulfilment striven for in the pursuit of commodity after commodity can be viewed as a desperate need to heal the self and, invariably, to find salvation. My understanding of the religious is discussed in a relationship between the sacred and the profane in the context of Durkheim and then Bataille, which leads me to the conclusion that compulsive buying is an implicitly religious activity.
From Season to Season. Sports as American Religion, edited by J.L. Price. Macon, GA: Mercer UP, 2001. 9780865546943 and The Great God Baseball. Religion in Modern Baseball Fiction, by A.E. Hye. Macon, GA: Mercer UP, 2004. 9780865549319
Authors: Grimshaw Michael
Published: November 2009

From Season to Season. Sports as American Religion, edited by Joseph L. Price. Macon, GA: Mercer University Press, 2001. ISBN-13: 9780865546943, 240pp., hb $45.00.

The Great God Baseball. Religion in Modern Baseball Fiction, by Allen E. Hye. Macon, GA: Mercer University Press, 2004. ISBN-13: 9780865549319, 192 pp., HB $40.00.
Desigualdades sociais na mortalidade cardiovascular precoce em um município de médio porte no Brasil
Authors: Nogueira Mário Círio , Ribeiro Luiz Cláudio , Cruz Oswaldo Gonçalves
Published: November 2009

As doenças cardiovasculares são a principal causa de morte em muitos países. No Brasil, a mortalidade por doenças cardiovasculares ocorre prematuramente em maior proporção do que em países ricos. Este estudo objetivou analisar a relação entre a mortalidade cardiovascular precoce e as condições sócio-econômicas no espaço urbano. Realizou-se um estudo ecológico, e as unidades de análise foram as regiões urbanas de um município da região sudeste de Minas Gerais. A relação entre a razão de mortalidade padronizada por doenças cardiovasculares e o Índice de Desenvolvimento Social (IDS) foi estudada por modelo linear generalizado com distribuição binomial negativa. Os bairros com melhores condições sócio-econômicas tiveram mortalidade por doenças cardiovasculares significantemente menor. A redução das desigualdades sócio-econômicas em cidades de médio porte pode contribuir para a redução das iniqüidades em saúde.
Rape Reporting: “Classic Rape” and the Behavior of Law
Authors: Clay-Warner Jody , McMahon-Howard Jennifer
Published: November 2009

Two theories of rape reporting, the Classic Rape perspective and Black’s Theory of the Behavior of Law, are tested in this article. We offer the first comprehensive multivariate test of Classic Rape predictions among a nationally representative sample of victims, as well as the first test of Black’s predictions for rape reporting. Through the construction of multinomial regression models, we are able to examine reporting patterns for both victims and third parties. Weapon use and physical injury consistently predicted reporting. The likelihood of victim reporting significantly increased when assaults occurred either in public or through a “home blitz,” whereas place of assault did not affect the likelihood of third-party reporting. On the other hand, victim–offender relationship significantly affected the likelihood of third-party reporting but was not significant in the victim-reporting models. There were mixed findings regarding Black’s stratification and morphology predictions, and we found no significant effects for culture, organization, or social control. Overall, these findings lend greater support to the Classic Rape perspective than to Black’s model.
Water-Injection Optimization for a Complex Fluvial Heavy-Oil Reservoir by Integrating Geological, Seismic, and Production Data
Authors: Feng Xin , Wen Xian-Huan , Li Bo , Liu Ming , Zhou Dengen , Ye Qiucheng , Huo Dongmei , Yang Qinghong , Lan Lichuan
Published: November 2009

BZ25-1s field in Bohai Bay, China, is characterized as a complex channelized fluvial reservoir in which small meandering channels were deposited at different geological times stacking and cross cutting each other. There are many isolated small reservoir systems following channel distributions. Early production showed steep pressure and production decline. Quick implementation of water injection was needed to arrest the fast production decline and to stabilize reservoir pressure.

While designing the water-injection plan, we faced a number of challenges, such as high oil viscosity (≈200 cp), strong heterogeneity, poor reservoir connectivity, complex channel geometry, and irregular well patterns. A workflow integrating geological, well-log, seismic, and dynamic production data was developed to optimize a water injection plan for this field after a short production history. Focuses of this workflow are the selection of injection wells (converted from existing producers), timing of water injection, and the optimization of injection rates.

Following the workflow, the optimal water-injection design for the areas around Platforms D and E was developed and quickly implemented within the first year of production. We started with a relatively small water-injection rate and gradually increased the injection rate to avoid the fast water breakthrough and yet to limit the pressure-decline rate.

The responses from the water injection were very positive and resulted in stable reservoir pressure and increase of oil production. Before water injection, the production-decline rates were 26 and 47% in Platforms D and E, respectively. After 1 year of water injection, oil-production-decline rates in these two platforms were reduced to 19 and 14%, respectively. The responses of water injection for different well groups were analyzed in a timely fashion and adjustments to injection/production strategies were implemented accordingly. New information revealed from the water-injection response analysis was used to update the geological model to reduce the model uncertainty, as well as to adjust the water-injection strategies for better sweep efficiency. Our experiences showed that such dynamic adjustment of injection and production schedule is very important to achieve better water-injection efficiency for this heavy-oil reservoir with complex channel geometry.