bluuebunny/crossref_metadata_2025 huggingface dataset:
A physical map for the Amborella trichopodagenome sheds light on the evolution of angiosperm genome structure
Authors: Zuccolo Andrea , Bowers John E , Estill James C , Xiong Zhiyong , Luo Meizhong , Sebastian Aswathy , Goicoechea José Luis , Collura Kristi , Yu Yeisoo , Jiao Yuannian , Duarte Jill , Tang Haibao , Ayyampalayam Saravanaraj , Rounsley Steve , Kudrna Dave , Paterson Andrew H , Pires J Chris , Chanderbali Andre , Soltis Douglas E , Chamala Srikar , Barbazuk Brad , Soltis Pamela S , Albert Victor A , Ma Hong , Mandoli Dina , Banks Jody , Carlson John E , Tomkins Jeffrey , dePamphilis Claude W , Wing Rod A , Leebens-Mack Jim
Published: May 2011

Background

Recent phylogenetic analyses have identified Amborella trichopoda, an understory tree species endemic to the forests of New Caledonia, as sister to a clade including all other known flowering plant species. The Amborella genome is a unique reference for understanding the evolution of angiosperm genomes because it can serve as an outgroup to root comparative analyses. A physical map, BAC end sequences and sample shotgun sequences provide a first view of the 870 Mbp Amborella genome.

Results

Analysis of Amborella BAC ends sequenced from each contig suggests that the density of long terminal repeat retrotransposons is negatively correlated with that of protein coding genes. Syntenic, presumably ancestral, gene blocks were identified in comparisons of the Amborella BAC contigs and the sequenced Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera and Oryza sativa genomes. Parsimony mapping of the loss of synteny corroborates previous analyses suggesting that the rate of structural change has been more rapid on lineages leading to Arabidopsis and Oryza compared with lineages leading to Populus and Vitis. The gamma paleohexiploidy event identified in the Arabidopsis, Populus and Vitis genomes is shown to have occurred after the divergence of all other known angiosperms from the lineage leading to Amborella.

Conclusions

When placed in the context of a physical map, BAC end sequences representing just 5.4% of the Amborella genome have facilitated reconstruction of gene blocks that existed in the last common ancestor of all flowering plants. The Amborella genome is an invaluable reference for inferences concerning the ancestral angiosperm and subsequent genome evolution.
The ShakeOut Scenario: Meeting the Needs for Construction Aggregates, Asphalt, and Concrete
Authors: Langer William H.
Published: May 2011

An Mw 7.8 earthquake as described in the ShakeOut Scenario would cause significant damage to buildings and infrastructure. Over 6 million tons of newly mined aggregate would be used for emergency repairs and for reconstruction in the five years following the event. This aggregate would be applied mostly in the form of concrete for buildings and bridges, asphalt or concrete for pavement, and unbound gravel for applications such as base course that goes under highway pavement and backfilling for foundations and pipelines. There are over 450 aggregate, concrete, and asphalt plants in the affected area, some of which would be heavily damaged. Meeting the increased demand for construction materials would require readily available permitted reserves, functioning production facilities, a supply of cement and asphalt, a source of water, gas, and electricity, and a trained workforce. Prudent advance preparations would facilitate a timely emergency response and reconstruction following such an earthquake.
Seismic Performance of Reinforced Concrete Frame Buildings in Southern California
Authors: Lynch Kathryn P. , Rowe Kristen L. , Liel Abbie B.
Published: May 2011

This study examines the impact of the ShakeOut earthquake on reinforced concrete (RC) frame structures in Southern California. The assessment uses synthetic ground motions and nonlinear dynamic analysis to evaluate 20 RC frame buildings hypothetically located at 735 sites throughout the region. Results show that older nonductile RC frame structures may collapse at 8% to 32% of the sites analyzed, especially in Palm Springs, Los Angeles, and San Bernardino. Modern code-conforming RC frame structures are predicted to collapse at fewer sites (1–11%), but modern midrise construction may be vulnerable in Los Angeles due to rupture directivity and basin effects. These seismic performance metrics can inform the development of policies for emergency response and for mitigating earthquake-induced collapse of existing RC frame buildings. The study further provides a prototype that can be used in developing future scenario studies that will benefit from ongoing research to improve building and seismological models.
Railroad Damage Scenario Development
Authors: Byers William G.
Published: May 2011

The approaches necessary for estimating earthquake effects on railroads are different for developing design criteria or post-earthquake response policies and for developing railroad damage scenarios. In developing design criteria or post-earthquake response policies, the probability of ground motions exceeding a particular level is a primary concern. Developing damage scenarios, on the other hand, involves describing hypothetical effects for assumed ground motions. The identification of potential problems is the greatest benefit of disaster scenario development to railroads. Developing the Great Southern California ShakeOut Scenario revealed areas in which advance planning and arrangements by the affected railroads could reduce delays in repair work or improve the efficiency of operation during recovery. These include arranging emergency waivers for permits and similar governmental requirements, developing arrangements to accommodate earthquake-related conflicts between commuter and freight operations, advance arrangements for emergency use of helicopters, and physically securing equipment at the San Bernardino dispatching center to reduce damage.
Developing a Scenario for Widespread Use: Best Practices, Lessons Learned
Authors: Perry Sue , Jones Lucile , Cox Dale
Published: May 2011

The ShakeOut Scenario is probably the most widely known and used earthquake scenario created to date. Much of the credit for its widespread dissemination and application lies with scenario development criteria that focused on the needs and involvement of end users and with a suite of products that tailored communication of the results to varied end users, who ranged from emergency managers to the general public, from corporations to grassroots organizations. Products were most effective when they were highly visual, when they emphasized the findings of social scientists, and when they communicated the experience of living through the earthquake. This paper summarizes the development criteria and the products that made the ShakeOut Scenario so widely known and used, and it provides some suggestions for future improvements.
Public Response to a Catastrophic Southern California Earthquake: A Sociological Perspective
Authors: Goltz James D. , Mileti Dennis S.
Published: May 2011

This paper describes a hypothetical scenario of public response to a large regional earthquake on the southern section of the San Andreas Fault. Conclusive social and behavioral science research over decades has established that the behavior of individuals in disaster is, on the whole, controlled, rational, and adaptive, despite popular misperceptions that people who experience a disaster are dependent upon and problematic for organized response agencies. We applied this knowledge to portray the response of people impacted by the earthquake focusing on actions they will take during and immediately following the cessation of the shaking including: immediate response, search and rescue, gaining situational awareness through information seeking, making decisions about evacuation and interacting with organized responders. Our most general conclusion is that the actions of ordinary people in this earthquake scenario comprised the bulk of the initial response effort, particularly in those areas isolated for lengthy periods of time following the earthquake.
Recovering from the ShakeOut Earthquake
Authors: Wein Anne , Johnson Laurie , Bernknopf Richard
Published: May 2011

Recovery from an earthquake like the M7.8 ShakeOut Scenario will be a major endeavor taking many years to complete. Hundreds of Southern California municipalities will be affected; most lack recovery plans or previous disaster experience. To support recovery planning this paper 1) extends the regional ShakeOut Scenario analysis into the recovery period using a recovery model, 2) localizes analyses to identify longer-term impacts and issues in two communities, and 3) considers the regional context of local recovery. Key community insights about preparing for post-disaster recovery include the need to: geographically diversify city procurement; set earthquake mitigation priorities for critical infrastructure (e.g., airport), plan to replace mobile homes with earthquake safety measures, consider post-earthquake redevelopment opportunities ahead of time, and develop post-disaster recovery management and governance structures. This work also showed that communities with minor damages are still sensitive to regional infrastructure damages and their potential long-term impacts on community recovery. This highlights the importance of community and infrastructure resilience strategies as well.
Estimating Surface Faulting Impacts from the ShakeOut Scenario Earthquake
Authors: Treiman Jerome A. , Ponti Daniel J.
Published: May 2011

An earthquake scenario, based on a kinematic rupture model, has been prepared for a Mw 7.8 earthquake on the southern San Andreas Fault. The rupture distribution, in the context of other historic large earthquakes, is judged reasonable for the purposes of this scenario. This model is used as the basis for generating a surface rupture map and for assessing potential direct impacts on lifelines and other infrastructure. Modeling the surface rupture involves identifying fault traces on which to place the rupture, assigning slip values to the fault traces, and characterizing the specific displacements that would occur to each lifeline impacted by the rupture. Different approaches were required to address variable slip distribution in response to a variety of fault patterns. Our results, involving judgment and experience, represent one plausible outcome and are not predictive because of the variable nature of surface rupture.
Utility Performance Panels in the ShakeOut Scenario
Authors: Porter Keith A. , Sherrill Rachel
Published: May 2011

The ShakeOut Scenario assessed earth-science impacts, physical damage, and socioeconomic impacts of a hypothetical M7.8 southern San Andreas Fault earthquake. Among many detailed studies were special studies of 12 lifelines, 7 of which were performed by panels of employees of the utilities at risk. Panels met for four hours. Panelists were presented with the scenario's earth science impacts and previously estimated damage to “upstream” lifelines. They then hypothesized a realistic outcome of the earthquake on damage and service restoration, identifying research needs and mitigation options. The panel process worked well: panelists were well qualified and seemed to fairly assess realistic earthquake impacts and restoration, probably more realistically than an outside consultant would have been able to do, thus improving the ShakeOut. Panelists gained insight into lifeline interaction, mutual-aid needs, communication capabilities, and backup supplies. Southern California Edison, for example, enhanced its planning and preparedness for a large Southern California earthquake.
Economic Impacts of the ShakeOut Scenario
Authors: Rose Adam , Wei Dan , Wein Anne
Published: May 2011

For the ShakeOut Earthquake Scenario, we estimate $68 billion in direct and indirect business interruption (BI) and $11 billion in related costs in addition to the $113 billion in property damage in an eight-county Southern California region. The modeled conduits of shock to the economy are property damage and lifeline service outages that affect the economy's ability to produce. Property damage from fire is 50% greater than property damage from shaking because fire is more devastating. BI from water service disruption and fire each represent around one-third of total BI losses because of the long duration of service outage or long restoration and reconstruction periods. Total BI losses are 4.3% of annual gross output in the affected region, an impact far larger than most conventional economic recessions. These losses are still much lower than they potentially could be due to the resilience of the economy.
Dialogues across the Continent: The Influence of Czesław Miłosz on Seamus Heaney
Authors: Kay Magdalena
Published: May 2011

This article analyzes the influence of Polish poet Czesław Miłosz on Northern Irish poet Seamus Heaney in reference to two poems — Miłosz's biographical, ethically self-critical “Bypassing Rue Descartes” and Heaney's ethical allegory “From the Republic of Conscience” — which serve as case studies to elucidate the way in which Milosz's poetic changes as it travels westward and influences Heaney's volume The Haw Lantern (1987). Heaney's experiments with the parable form, and his corollary desire to bring the “aerated” language of abstractions into a poetry based on concrete experience, are conducted under the aegis of Miłosz, his “Master.” These experiments are not historically neutral, and the political dimension of Miłosz's poetic meditation is not lost upon Heaney, whose own desire is to forge a poetic more de-materialized than that of his previous volumes North (1975) and Field Work (1979). His view of Miłosz, however, is affected by associations against which Miłosz himself rebels. Most notable for this comparison is Miłosz's insistence that “noble feelings” are dangerous for literature and — in spite of his avowed anti-Romanticism — his bardic aura. Heaney's experience with Miłosz must be seen in the cultural context with which each poet was associated and in the context of Heaney's desire at the time to attune himself to Eastern European poetry in general and to his “Master” in particular. This article first situates Heaney's encounter with Miłosz in literary-historical and biographical space, then closely compares the two poems at hand, and, finally, considers the sort of transnational reading strategy that these poems demand.
Listening: Jean-Luc Nancy and the “Anti-Ocular” Turn in Continental Philosophy and Critical Theory
Authors: Janus Adrienne
Published: May 2011

This essay analyzes Jean-Luc Nancy's recent work À L'Écoute (2002)/Listening (2007) as a culminating moment in what might be called the “anti-ocular” turn in Continental philosophy. It situates Nancy within a genealogy of “otocentric” thinkers that includes Martin Heidegger, Peter Sloterdijk, Jacques Attali, Didier Anzieu, and Luce Irigary. These figures not only present a critique of vision as the dominant paradigm in Western thought, but also develop a positive alternative model of listening that offers the possibility of reintegrating modes of sensual perception excluded by “ocularcentrism” and the conceptual abstraction associated with it. As exemplified by Martin Jay's otherwise admirable “synoptic survey” of “anti-ocularcentric” discourse in twentieth-century French thought, however, the importation and translation of these “otocentric” figures into the field of Anglophone critical theory — when they are acknowledged at all — tends to allow the visual paradigm to reassert itself, if only as the object of endless deconstructive critique.
Ovarian metabolism of xenobiotics
Authors: Bhattacharya Poulomi , Keating Aileen F
Published: May 2011

At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial follicles resulting in premature ovarian failure and, consequently, early entry into menopause. A number of chemical classes can induce premature ovarian failure, including environmental, chemotherapeutic and industrial exposures. While our knowledge on the mechanistic events that occur in the ovary with chemical exposures is increasing, our understanding of the ovary's capacity to metabolize such compounds is less established. This review will focus on three chemicals for which information on ovarian metabolism is known: trichloroethylene, 7,12-dimethylbenz[a]anthracene and 4-vinylcyclohexene. The current state of understanding of ovarian bioactivation and detoxification processes for each will be described.
Epithelial Membrane Protein-2 Promotes Endometrial Tumor Formation through Activation of FAK and Src
Authors: Fu Maoyong , Rao Rajiv , Sudhakar Deepthi , Hogue Claire P. , Rutta Zach , Morales Shawn , Gordon Lynn K. , Braun Jonathan , Goodglick Lee , Wadehra Madhuri
Published: May 2011

Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2), a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK)/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.
Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus
Authors: Sacks David B , Arnold Mark , Bakris George L , Bruns David E , Horvath Andrea Rita , Kirkman M Sue , Lernmark Ake , Metzger Boyd E , Nathan David M
Published: May 2011

BACKGROUND

Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially.

APPROACH

An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence Based Laboratory Medicine Committee of the AACC jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association.

CONTENT

In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A1c (Hb A1c) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed.

The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended.
Endocrine cells and blood vessels work in tandem to generate hormone pulses
Authors: Schaeffer Marie , Hodson David J , Lafont Chrystel , Mollard Patrice
Published: May 2011

Hormones are dynamically collected by fenestrated capillaries to generate pulses, which are then decoded by target tissues to mount a biological response. To generate hormone pulses, endocrine systems have evolved mechanisms to tightly regulate blood perfusion and oxygenation, coordinate endocrine cell responses to secretory stimuli, and regulate hormone uptake from the perivascular space into the bloodstream. Based on recent findings, we review here the mechanisms that exist in endocrine systems to regulate blood flow, and facilitate coordinated cell activity and output under both normal physiological and pathological conditions in the pituitary gland and pancreas.
High‐Dose Daptomycin for Treatment of Complicated Gram‐Positive Infections: A Large, Multicenter, Retrospective Study
Authors: Kullar Ravina , Davis Susan L. , Levine Donald P. , Zhao Jing J. , Crank Christopher W. , Segreti John , Sakoulas George , Cosgrove Sara E. , Rybak Michael J.
Published: May 2011

Study Objective. To evaluate the clinical response and safety of high‐dose daptomycin for treatment of complicated gram‐positive infections.

Design. Multicenter, retrospective, observational, case series analysis.

Setting. Five academic medical centers in four major United States cities.

Patients. Two hundred fifty adults, not undergoing dialysis, who received high‐dose daptomycin (≥ 8 mg/kg/day) for at least 72 hours for complicated gram‐positive infections between January 1, 2005, and March 1, 2010.

Measurements and Main Results. Clinical and microbiologic outcomes were assessed at the end of high‐dose daptomycin therapy. Safety evaluations were recorded for all patients, and when available, baseline, end‐of‐therapy and highest observed serum creatine phosphokinase (CPK) levels were recorded. Methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococcusfaecium (VRE) were the primary organisms isolated. The median dose of daptomycin was 8.9 mg/kg/day (interquartile range [IQR] 8.0–10.0 mg/kg/day). The median duration of daptomycin during hospitalization for MRSA and VRE infection was 10 days (IQR 5–16 days) and 13 days (IQR 6–18 days), respectively. Among the 250 patients, high‐dose daptomycin was primarily used as salvage therapy after vancomycin treatment (184 patients [73.6%]). Primary infections included complicated bacteremia (119 patients [47.6%]), endocarditis (59 [23.6%]), skin or wound (70 [28.0%]), and bone or joint (67 [26.8%]). Overall, clinical response and microbiologic success were assessed in 83.6% (209/250 patients) and 80.3% (175/218 patients), respectively. Isolates from 13 patients (5.2%) developed nonsusceptibility to daptomycin, with most of these patients having extended vancomycin exposure. Three patients (1.2%) developed an adverse event attributable to high‐dose daptomycin therapy, with the event considered either mild or moderate in severity. The median end‐of‐therapy CPK level was 39 U/L (IQR 26–67 U/L). No significant correlation was found between daptomycin dose and highest observed CPK level.
Comparison of Rate Control versus Rhythm Control for Management of Atrial Fibrillation in Patients with Coexisting Heart Failure: A Cost‐Effectiveness Analysis
Authors: Perez Alexandra , Touchette Daniel R. , DiDomenico Robert J. , Stamos Thomas D. , Walton Surrey M.
Published: May 2011

Study Objective. To compare lifetime costs and health outcomes of rate control versus rhythm control for management of atrial fibrillation in patients with coexisting heart failure from the third‐party payer perspective.

Design. A Markov decision analysis model constructed from costs, utility, and transition probability inputs obtained from randomized clinical trials and publically available databases.

Patients. A simulated cohort aged 65 years or older with persistent or paroxysmal atrial fibrillation and heart failure.

Measurements and Main Results. Markov states for rhythm control were cardioversion plus amiodarone and maintenance amiodarone, and those for rate control were β‐blocker, digoxin, and calcium channel blocker. Transition states included treatment success, hospitalizations for atrial fibrillation and/or heart failure, and severe adverse effects. Economic inputs included cost for drugs, cost of hospitalizations for atrial fibrillation and/or heart failure, and cost of management of severe adverse effects. Costs were measured in 2009 U.S. dollars, and clinical outcomes in quality‐adjusted life‐years (QALYs). One‐way and multivariable sensitivity analyses were conducted. Uncertainty intervals (UIs) were obtained from probabilistic sensitivity analyses. Rate control was found to be less costly and more effective than rhythm control. Base case and probabilistic sensitivity analyses cost and effectiveness values for rate control were $7231 (95% UI $5517–9016) and 2.395 QALYs (95% UI 2.366–2.424 QALYs); whereas those for rhythm control were $16,291 (95% UI $11,033–21,434) and 2.197 QALYs (95% UI 2.155–2.237 QALYs). No critical values were found for any model parameters in the one‐way sensitivity analyses. The cost‐effectiveness acceptability curves showed that rate control was considered cost‐effective in 100% of cases at willingness‐to‐pay ratios between $0 and $200,000/QALY.

Conclusion. Rate control is less costly and more effective than rhythm control and should be the initial treatment for atrial fibrillation among patients with coexisting heart failure.
Population Pharmacokinetics of Cyclosporine in Korean Adults Undergoing Living‐Donor Kidney Transplantation
Authors: Ji Eunhee , Kim Mi‐Young , Yun Hwi‐Yeol , Kim Kyung Im , Kang Wonku , Kwon Kwang‐Il , Kim In‐Wha , Lee Hye Suk , Shin Wan Gyoon , Oh Jung Mi
Published: May 2011

Study Objective. To estimate the population pharmacokinetic parameters of cyclosporine in Korean adults undergoing living‐donor kidney transplantation, and to identify clinical factors affecting cyclosporine pharmacokinetics.

Design. Retrospective cohort study.

Setting. Single, 1600‐bed, tertiary care academic medical center in Seoul, South Korea.

Patients. Seventy‐four living‐donor kidney transplant recipients (mean age 42 yrs) receiving oral cyclosporine microemulsion as an immunosuppressant between January 1, 2001, and August 31, 2006.

Measurements and Main Results. Using nonlinear mixed‐effects modeling (NONMEM) with first‐order absorption and elimination, a total of 2394 whole‐blood cyclosporine concentrations from the 74 patients were analyzed. The effects of several clinical covariates on cyclosporine pharmacokinetic parameters were evaluated over 12 months after transplantation. The absorption rate constant was fixed at 1.28 hour−1, and the following population pharmacokinetic estimates were calculated: cyclosporine clearance 43.6 L/hour, apparent volume of distribution 1990 L, and interpatient variability for clearance (coefficient of variation) 17.69%. The clinical factors (covariates) that significantly affected cyclosporine pharmacokinetics were postoperative days, prednisolone dose (in mg/day), total bilirubin level (mg/dl), current body weight (in kg), and concurrent use of amlodipine.

Conclusion. This population pharmacokinetic model identified important sources of variability in cyclosporine pharmacokinetics. The model will help calculate cyclosporine dose requirements in renal transplant recipients according to specific clinical factors affecting cyclosporine clearance, and it will also be useful for therapeutic drug monitoring.
Potential for Linezolid‐Related Blindness: A Review of Spontaneous Adverse Event Reports
Authors: Brown Jack , Aitken Samuel L. , van Manen Robbert P.
Published: May 2011

Study Objective. To provide clinicians with an understanding of the comparative occurrence of linezolid and blindness, and to provide any clinically relevant characteristics that may be useful in identifying the patients at risk.

Design. Retrospective cohort study.

Data Source. Spontaneous reports in the United States Food and Drug Administration Adverse Event Reporting System (AERS) database generated between November 1, 1997, and December 21, 2008.

Patients. Twenty‐nine patients who experienced blindness while receiving linezolid therapy.

Measurements and Main Results. Available information related to each case of linezolid‐reported blindness in the AERS database was qualitatively and quantitatively reviewed. Optic nerve disorders, glaucoma, and treatment with linezolid for long durations were common characteristics in patients experiencing blindness. A limitation of AERS is the lack of a quantitative exposure estimate to put rare adverse events of the AERS, such as linezolid‐related blindness, into perspective. To overcome this limitation, disproportionality analysis with Bayesian correction methodology was used. Disproportionality analysis uses an adverse event relative reporting ratio (RRR) to compare the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA‐approved prescription drugs. The disproportionality analysis was considered meaningful if the 5th percentile of the distribution of the RRR (RRR05) was 2 or greater. Among the 29 reported cases of linezolid use and blindness, an RRR05 of 2.1 was determined for linezolid‐related blindness compared with all other agents listed in the AERS. Also, RRR05 values of 2.7 and 2.2 were found when linezolid was compared with all other systemic antibiotics and a select subgroup of antibiotics, respectively.

Conclusion. Although disproportionality analyses suggested a quantitative signal for an association between linezolid use and blindness, causality cannot be inferred from the data. Thus, additional rigorous scientific analyses are warranted to explore these findings.
Effect of Acetaminophen on International Normalized Ratio in Patients Receiving Warfarin Therapy
Authors: Hughes Gregory J. , Patel Priti N. , Saxena Neera
Published: May 2011

Warfarin is known to have extensive interactions with many classes of drugs. The literature suggesting a relevant interaction between acetaminophen and warfarin is inconsistent. Considering the ubiquitous use of acetaminophen, a review of the effects on international normalized ratio (INR) in patients taking warfarin was necessary. Thus, we performed a search of the PubMed (1966‐November 2010) and International Pharmaceutical Abstracts (1970‐November 2010) databases to review the available literature addressing an acetaminophen‐warfarin interaction and its possible mechanisms. A sample of case reports, in addition to all English‐language studies were evaluated, and relevant references were examined for additional articles. Reports of nonwarfarin coumarin anticoagulants were excluded. Published documentation reporting an interaction between acetaminophen and warfarin is limited. Small prospective studies of various designs and case studies describe aberrant INR results in patients using acetaminophen while receiving warfarin. These INR elevations typically involved acetaminophen ingestion of at least 2 g/day for several consecutive days. In several small prospective studies, INR results were elevated to a statistically significant extent that would require a change in warfarin dosing and monitoring in clinical practice. The mechanism for this interaction remains to be elucidated yet is suggested to occur through alterations in hepatic metabolism. The use of moderate‐to‐high doses of acetaminophen while receiving warfarin results in supra‐therapeutic INRs in some patients. The characteristics that may predispose a patient to this interaction are unclear, yet the widespread use of acetaminophen calls for enhanced clinician awareness and reinforcement of patient education about this interaction.
Montrose Field Reservoir Management
Authors: Bishlawi Morad , Moore Robert L.
Published: May 2011

The Montrose Field, one of the earliest oil discoveries in the UK sector of the North Sea, was put on production in 1976. The Field is operated by Amoco for the Amoco/Gas Council Group, a group of companies comprised of the British Gas Corporation, Texas Eastern and Amerada Hess in addition to Amoco. Extensive reservoir pressure data collection from the start of production enabled the Amoco/Gas Council Group to develop a reservoir depletion policy that was by no means obvious from reservoir studies completed prior to the start of production and is believed will result in the maximum recovery of oil. The reservoir pressure data gathered included conventional bottomhole shut-in pressure buildup surveys plus, in all wells drilled since 1977, Repeat Formation Tester (RFT)* pressure surveys; a tool which has only recently been found to be a strong aid in reservoir evaluation and in developing a sound reservoir management policy.
Impact of Fruit Ripeness on Physicochemical Properties and Convective Drying Characteristics of Kent Mango (Mangifera indica L. cv. 'Kent')
Authors: Dissa Alfa Oumar , Desmorieux Hélène , Degraeve Pascal , Bathiebo Joseph , Koulidiati Jean
Published: May 2011

Impact of ripeness on drying characteristics of mango was studied by considering different zones on the fruit. For each zone, ripeness was estimated by total soluble solids/acidity ratio, colour and texture of fruit flesh. For each state of ripeness, drying curves and time-temperature curves were established both in forced and natural convection. Mass diffusivity (estimated by considering two diffusion regions), thermal diffusivity and drying rates were deduced from these drying curves by considering product shrinkage. Results showed that the time required to reduce moisture content to any given level depended on the ripeness state, being highest for unripe samples and lowest for ripe samples. At each drying moment, temperature of ripe sample was higher than that of unripe sample. Mass diffusivity, thermal diffusivity and drying rates strongly increased with ripeness state. At 60°C, unripe and ripe fruit mass diffusivities ranged respectively from 1.69x10-10 to 9.87x10-10 m²/s and 3.38x10-10 to 1.77x10-9 m²/s. Thermal diffusivities ranged from 2.12 x10-11 to 6.44x10-10 m²/s and 2.74x10-10 to 8.05 x10-10 m²/s respectively for unripe and ripe samples. In natural convection, drying rates reached maximal values of 0.16 kg m-2 s for unripe sample and 0.47 kg m-2 s for ripe sample whereas in forced convection they reached respectively 0.43 and 0.67 kg m-2 s. Product shrinkage decreased with ripeness and was almost ideal for the major part of the drying process. Constants of suitable fitting models also varied considerably with fruit ripeness. This work showed that ripeness state influences strongly drying characteristics of mango fruit.
Cost-Effectiveness Analysis of a Randomized Trial Comparing Care Models for Chronic Kidney Disease
Authors: Hopkins Robert B. , Garg Amit X. , Levin Adeera , Molzahn Anita , Rigatto Claudio , Singer Joel , Soltys George , Soroka Steven , Parfrey Patrick S. , Barrett Brendan J. , Goeree Ron
Published: May 2011

Background and objectives

Potential cost and effectiveness of a nephrologist/nurse–based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease.

Design, setting, participants, & measurements

Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist–supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs.

Results

Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR.

Conclusions

The nephrologist/nurse–based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.
Active Vitamin D and Acute Respiratory Infections in Dialysis Patients
Authors: Tsujimoto Yoshihiro , Tahara Hideki , Shoji Tetsuo , Emoto Masanori , Koyama Hidenori , Ishimura Eiji , Tabata Tsutomu , Nishizawa Yoshiki , Inaba Masaaki
Published: May 2011

Background and objectives

Vitamin D has gained attention for its pleiotropic effects in areas other than bone metabolism, and the effects of vitamin D in preventing respiratory infections have been reported as one of its immunomodulating properties. This study assessed the preventive effect of vitamin D receptor activator (VDRA) on respiratory infections in dialysis patients.

Design, setting, participants, & measurements

Maintained Japanese hemodialysis patients (n = 508) were observed for 5 years, and the incidence of hospitalization during this period because of acute respiratory infection (ARI) was recorded.

Results:

Of the 508 patients, 212 had taken oral VDRA at the start of the study, whereas 296 patients had not received it. During the 5-year follow-up period, 57 patients were hospitalized because of ARIs. Kaplan–Meier analysis revealed that the incidence of hospitalization because of respiratory infection was significantly lower in patients who had been treated with VDRA compared with patients who had not (log rank test; P = 0.02). The multivariate Cox proportional hazards model demonstrated that the patients who had taken oral VDRA were at a significantly lower risk of hospitalization because of respiratory disease (hazard ratio 0.47, 95% confidence interval 0.25 to 0.90).

Conclusions:

The findings of this study suggest that the administration of oral VDRA has a preventive effect on the incidence of ARIs in dialysis patients.
Pre-emptive Eculizumab and Plasmapheresis for Renal Transplant in Atypical Hemolytic Uremic Syndrome
Authors: Nester Carla , Stewart Zoe , Myers David , Jetton Jennifer , Nair Ramesh , Reed Alan , Thomas Christie , Smith Richard , Brophy Patrick
Published: May 2011

The case of a 12-year-old with a hybrid CFH/CFHL1 gene and atypical hemolytic uremic syndrome (aHUS) that had previously developed native kidney and then renal allograft loss is reported. This case illustrates the relatively common occurrence of renal loss from the late presentation of aHUS. Also presented is a protocol for the pre-emptive use of eculizumab and plasmapheresis as part of a renal transplant plan for the treatment of aHUS in patients deemed at high risk for recurrent disease. This protocol was a result of a multidisciplinary approach including adult and pediatric nephrology, transplant surgery, transfusion medicine, and infectious disease specialists. This protocol and the justifications and components of it can function as a guideline for the treatment of a group of children that have waited in limbo for the first U.S. transplant to open the door to this type of definitive care for this devastating disease.
Spinal Epidural Abscess in Hemodialysis Patients
Authors: Wong San S. , Daka Smitha , Pastewski Andrew , Kyaw Win , Chapnick Edward , Sepkowitz Douglas
Published: May 2011

Spinal epidural abscess (SEA) is a rare but potentially devastating condition. We noticed an increase in the number of cases of SEA, with the majority in hemodialysis (HD) patients. This prompted a retrospective chart review of all cases of SEA admitted from 2000 to 2005 and a literature search of similar cases. We identified 19 SEA cases treated at Long Island College Hospital during this 6-year period, of which six were on HD: four were dialyzed via catheter, one via arteriovenous fistula, and in one the method of dialysis was not documented. Four patients had bacteremia with Staphylococcus aureus. Four patients presented with paresis or paralysis; only one improved. The mortality rate was 33% (2/6). We found 30 other cases of SEA in patients on HD from the literature. These 36 HD cases were compared with 85 SEA cases that were not on HD (13 from our study and 72 described in two large case series). The mortality rate was noted to be much higher in HD patients (23% [6/26] versus 7% [6/85]). Neurologic deficit at presentation was noted in 47% (17/36) of HD patients versus 69% (59/85) of non-HD patients, but neurologic improvement was higher in non-HD patients (71% [42/59] versus 29% [5/17]). This is the largest literature review of SEA in patients on HD. When compared with non-HD patients, HD patients had a higher mortality rate and were less likely to improve neurologically.
Thrombospondin-1: An Islet Endothelial Cell Signal of Importance for β-Cell Function
Authors: Olerud Johan , Mokhtari Dariush , Johansson Magnus , Christoffersson Gustaf , Lawler Jack , Welsh Nils , Carlsson Per-Ola
Published: May 2011

OBJECTIVE

Loss of thrombospondin (TSP)-1 in pancreatic islets has been shown to cause islet hyperplasia. This study tested the hypothesis that endothelial-derived TSP-1 is important for β-cell function.

RESEARCH DESIGN AND METHODS

Islet function was evaluated both in vivo and in vitro. Messenger RNA and protein expression were measured by real-time PCR and Western blot, respectively. The role of endothelial-derived TSP-1 for β-cell function was determined using a transplantation design in which recipient blood vessels either were allowed to grow or not into the transplanted islets.

RESULTS

TSP-1–deficient mice were glucose intolerant, despite having an increased β-cell mass. Moreover, their islets had decreased glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate, as well as increased expression of uncoupling protein-2 and lactate dehydrogenase-A when compared with control islets. Almost all TSP-1 in normal islets were found to be derived from the endothelium. Transplantation of free and encapsulated neonatal wild-type and TSP-1–deficient islets was performed in order to selectively reconstitute with TSP-1–positive or –negative blood vessels in the islets and supported that the β-cell defects occurring in TSP-1–deficient islets reflected postnatal loss of the glycoprotein in the islet endothelial cells. Treatment of neonatal TSP-1–deficient mice with the transforming growth factor (TGF)β-1–activating sequence of TSP-1 showed that reconstitution of TGFβ-1 activation prevented the development of decreased glucose tolerance in these mice. Thus, endothelial-derived TSP-1 activates islet TGFβ-1 of importance for β-cells.

CONCLUSIONS

Our study indicates a novel role for endothelial cells as functional paracrine support for pancreatic β-cells.
Genetic Defect in Phospholipase Cδ1 Protects Mice From Obesity by Regulating Thermogenesis and Adipogenesis
Authors: Hirata Masayuki , Suzuki Mutsumi , Ishii Rika , Satow Reiko , Uchida Takafumi , Kitazumi Tomoya , Sasaki Tsutomu , Kitamura Tadahiro , Yamaguchi Hideki , Nakamura Yoshikazu , Fukami Kiyoko
Published: May 2011

OBJECTIVE

Regulation of obesity development is an important issue to prevent metabolic syndromes. Gene-disrupted mice of phospholipase Cδ1 (PLCδ1), a key enzyme of phosphoinositide turnover, seemed to show leanness. Here we examined whether and how PLCδ1 is involved in obesity.

RESEARCH DESIGN AND METHODS

Weight gain, insulin sensitivity, and metabolic rate in PLCδ1−/− mice were compared with PLCδ1+/− littermate mice on a high-fat diet. Thermogenic and adipogenetic potentials of PLCδ1−/− immortalized brown adipocytes and adipogenesis of PLCδ1-knockdown (KD) 3T3L1 cells, or PLCδ1−/− white adipose tissue (WAT) stromal-vascular fraction (SVF) cells, were also investigated.

RESULTS

PLCδ1−/− mice showed marked decreases in weight gain and mass of epididymal WAT and preserved insulin sensitivity compared with PLCδ1+/− mice on a high-fat diet. In addition, PLCδ1−/− mice have a higher metabolic rate such as higher oxygen consumption and heat production. When control immortalized brown adipocytes were treated with thermogenic inducers, expression of PLCδ1 was decreased and thermogenic gene uncoupling protein 1 (UCP1) was upregulated to a greater extent in PLCδ1−/− immortalized brown adipocytes. In contrast, ectopic expression of PLCδ1 in PLCδ1−/− brown adipocytes induced a decrease in UCP expression, indicating that PLCδ1 negatively regulates thermogenesis. Importantly, accumulation of lipid droplets was severely decreased when PLCδ1-KD 3T3L1 cells, or PLCδ1−/− WAT SVF cells, were differentiated, whereas differentiation of PLCδ1−/− brown preadipocytes was promoted.

CONCLUSIONS

PLCδ1 has essential roles in thermogenesis and adipogenesis and thereby contributes to the development of obesity.
Transcriptional Profiling of Diabetic Neuropathy in the BKS db/db Mouse
Authors: Pande Manjusha , Hur Junguk , Hong Yu , Backus Carey , Hayes John M. , Oh Sang Su , Kretzler Matthias , Feldman Eva L.
Published: May 2011

OBJECTIVE

A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve.

RESEARCH DESIGN AND METHODS

Microarray data for 24-week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further analyzed to identify regulated biological processes and pathways. Expression profile clustering was performed to identify coexpressed DEGs. A set of coexpressed lipid metabolism genes was used for promoter sequence analysis.

RESULTS

Gene expression changes are consistent with structural changes of axonal degeneration. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, peroxisome proliferator–activated receptor signaling, apoptosis, and axon guidance. Promoter sequences of lipid metabolism–related genes exhibit evidence of coregulation of lipid metabolism and nervous system development genes.

CONCLUSIONS

Our data support existing hypotheses regarding hyperglycemia-mediated nerve damage in DN. Moreover, our analyses revealed a possible coregulation mechanism connecting hyperlipidemia and axonal degeneration.