bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep RNA sequencing of L. monocytogenes reveals overlapping and extensive stationary phase and sigma B-dependent transcriptomes, including multiple highly transcribed noncoding RNAs
Authors: Oliver Haley F , Orsi Renato H , Ponnala Lalit , Keich Uri , Wang Wei , Sun Qi , Cartinhour Samuel W , Filiatrault Melanie J , Wiedmann Martin , Boor Kathryn J
Published: December 2009

Background

Identification of specific genes and gene expression patterns important for bacterial survival, transmission and pathogenesis is critically needed to enable development of more effective pathogen control strategies. The stationary phase stress response transcriptome, including many σB-dependent genes, was defined for the human bacterial pathogenListeria monocytogenesusing RNA sequencing (RNA-Seq) with the Illumina Genome Analyzer. Specifically, bacterial transcriptomes were compared between stationary phase cells ofL. monocytogenes10403S and an otherwise isogenic ΔsigBmutant, which does not express the alternative σ factor σB, a major regulator of genes contributing to stress response, including stresses encountered upon entry into stationary phase.

Results

Overall, 83% of allL. monocytogenesgenes were transcribed in stationary phase cells; 42% of currently annotatedL. monocytogenesgenes showed medium to high transcript levels under these conditions. A total of 96 genes had significantly higher transcript levels in 10403S than in ΔsigB, indicating σB-dependent transcription of these genes. RNA-Seq analyses indicate that a total of 67 noncoding RNA molecules (ncRNAs) are transcribed in stationary phaseL. monocytogenes, including 7 previously unrecognized putative ncRNAs. Application of a dynamically trained Hidden Markov Model, in combination with RNA-Seq data, identified 65 putative σBpromoters upstream of 82 of the 96 σB-dependent genes and upstream of the one σB-dependent ncRNA. The RNA-Seq data also enabled annotation of putative operons as well as visualization of 5'- and 3'-UTR regions.

Conclusions

The results from these studies provide powerful evidence that RNA-Seq data combined with appropriate bioinformatics tools allow quantitative characterization of prokaryotic transcriptomes, thus providing exciting new strategies for exploring transcriptional regulatory networks in bacteria.

See minireivewhttp://jbiol.com/content/8/12/107.
Virus infection elevates transcriptional activity of miR164a promoter in plants
Authors: Bazzini Ariel A , Almasia Natalia I , Manacorda Carlos A , Mongelli Vanesa C , Conti Gabriela , Maroniche Guillermo A , Rodriguez María C , Distéfano Ana J , Hopp H Esteban , del Vas Mariana , Asurmendi Sebastian
Published: December 2009

Background

Micro RNAs (miRs) constitute a large group of endogenous small RNAs that have crucial roles in many important plant functions. Virus infection and transgenic expression of viral proteins alter accumulation and activity of miRs and so far, most of the published evidence involves post-transcriptional regulations.

Results

Using transgenic plants expressing a reporter gene under the promoter region of a characterized miR (P-miR164a), we monitored the reporter gene expression in different tissues and during Arabidopsis development. Strong expression was detected in both vascular tissues and hydathodes. P-miR164a activity was developmentally regulated in plants with a maximum expression at stages 1.12 to 5.1 (according to Boyes, 2001) along the transition from vegetative to reproductive growth. Upon quantification of P-miR164a-derived GUS activity after Tobacco mosaic virus Cg or Oilseed rape mosaic virus (ORMV) infection and after hormone treatments, we demonstrated that ORMV and gibberellic acid elevated P-miR164a activity. Accordingly, total mature miR164, precursor of miR164a and CUC1 mRNA (a miR164 target) levels increased after virus infection and interestingly the most severe virus (ORMV) produced the strongest promoter induction.

Conclusion

This work shows for the first time that the alteration of miR pathways produced by viral infections possesses a transcriptional component. In addition, the degree of miR alteration correlates with virus severity since a more severe virus produces a stronger P-miR164a induction.
Design and methods for testing a simple dietary message to improve weight loss and dietary quality
Authors: Merriam Philip A , Ma Yunsheng , Olendzki Barbara C , Schneider Kristin L , Li Wenjun , Ockene Ira S , Pagoto Sherry L
Published: December 2009

Background

The current food pyramid guidelines have been criticized because of their complexity and the knowledge required for users to understand the recommendations. Simplification of a dietary message to focus on a single key aspect of dietary quality, e.g., fiber intake, may make the message much easier to comprehend and adhere, such that respondents can achieve greater weight loss, better dietary quality and overall metabolic health.

Methods and design

This is a randomized controlled clinical trial with two equal sized arms. In total, 240 obese adults who meet diagnostic criteria for the metabolic syndrome will be randomized to one of the two conditions: 1) a high fiber diet and 2) the American Heart Association (AHA) diet. In the high fiber diet condition, patients will be given instruction only on achieving daily dietary fiber intake of 30 g or more. In the AHA diet condition, patients will be instructed to make the several dietary changes recommended by the AHA 2006 guidelines. The trial examines participant weight loss and dietary quality as well as changes in components of the metabolic syndrome, inflammatory biomarkers, low-density lipoprotein cholesterol levels, insulin levels, and glycosolated hemoglobin. Potential mediators, i.e., diet adherence and perceived ease of the diet, and the intervention effect on weight change will also be examined.

Discussions

The purpose of this paper is to outline the study design and methods for testing the simple message of increasing dietary fiber. If the simple dietary approach is found efficacious for weight loss; and, improves dietary quality, metabolic health, and adherence, it might then be used to develop a simple public health message.

Trial registration

NCT00911885
A novel scoring system for prognostic prediction in d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure BALB/c mice
Authors: Feng Bo , Wu Sheng Ming , Lv Sa , Liu Feng , Chen Hong Song , Gao Yan , Dong Fang Ting , Wei Lai
Published: December 2009

Background

It is frequently important to identify the prognosis of fulminant hepatic failure (FHF) patients as this will influence patient management and candidacy for liver transplantation. Therefore, a novel scoring system based on metabonomics combining with multivariate logistic regression was developed to predict the prognosis of FHF mouse model.

Methods

BALB/c mice were used to construct FHF model. Parts of plasma were collected at 4, 5, and 6-h time points after treatment, respectively, and detected using gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). The acquired data were processed using partial least square discriminant analysis (PLS-DA). The metabolic markers identified were used to construct a scoring system by multivariate regression analysis.

Results

28 mice of survival group and 28 of dead group were randomly selected and analyzed. PLS regression analysis showed that both the PLS models of 5 h and 6 h after d-galactosamine/lipopolysaccharide treatment demonstrated good performances. Loadings plot suggested that phosphate, beta-hydroxybutyrate (HB), urea, glucose and lactate concentrations in plasma had the highest weightings on the clustering differences at the three time points. By the multivariate logistic regression analysis, the death/survival index (DSI) was constructed based on relative concentrations of HB, urea and phosphate. It provided general accurate rate of prediction of 93.3% in the independent samples.

Conclusions

The novel scoring system based on metabonomics combining with multivariate logistic regression is accurate in predicting the prognosis of FHF mouse model and may be referred in clinical practice as a more useful prognostic tool with other available information.
Incarceration experiences among a community-recruited sample of injection drug users in Bangkok, Thailand
Authors: Hayashi Kanna , Milloy M-J , Fairbairn Nadia , Kaplan Karyn , Suwannawong Paisan , Lai Calvin , Wood Evan , Kerr Thomas
Published: December 2009

Background

Since 2003 Thailand has waged an aggressive "war on drugs" campaign focused on arresting and incarcerating suspected drug users and dealers. However, little is known about incarceration experiences among IDU in the wake of the recent war on drugs. Therefore, we sought to examine incarceration experiences among IDU in Bangkok, Thailand.

Methods

We examined the prevalence of incarceration among community-recruited IDU participating in the Mitsampan Community Research Project. Multivariate logistic regression was used to identify factors associated with a self-reported history of incarceration. We also examined the prevalence of injection drug use and syringe sharing within prisons.

Results

252 IDU were recruited in August 2008; 66 (26.2%) were female and the median age was 36.5 years. In total, 197 (78.2%) participants reported a history of incarceration. In multivariate analyses, reporting a history of incarceration was associated with a history of compulsory drug treatment (adjusted odds ratio [AOR] = 4.93; 95% confidence interval [CI]: 1.95 - 12.48), non-fatal overdose (AOR = 3.69; 95%CI: 1.45 - 9.39), syringe sharing (AOR = 2.20; 95%CI: 1.12 - 4.32), and female gender (AOR = 0.41; 95%CI: 0.20 - 0.82). Among those who reported a history of incarceration, 59 (29.9%) reported injection drug use in prison, and 48 (81.4%) of these individuals reported sharing syringes in prison. Incarceration was not associated with the number of injections performed in the previous week (p = 0.202).

Conclusion

Over three-quarters of the IDU participating in this study reported a history of incarceration, and 30% of these individuals reported injection drug use within prison. Further, an alarmingly high level of syringe sharing within prison was reported, and incarceration was not associated with reductions in drug use. These findings provide further evidence of the need for community diversion strategies, as well as harm reduction programs, in Thai prisons.
Aminoguanidine inhibits aortic hydrogen peroxide production, VSMC NOX activity and hypercontractility in diabetic mice
Authors: Oak Jeong-Ho , Youn Ji-Youn , Cai Hua
Published: December 2009

Background

Dysfunctionally uncoupled endothelial nitric oxide synthase (eNOS) is involved in producing reactive oxygen species (ROS) in the diabetic endothelium. The present study investigated whether anti-diabetes drug Aminoguanidine (AG) has any effect on eNOS function and vascular oxidant stress.

Methods and Results

Blood glucose levels were increased to 452.0 ± 15.1 mg/dl in STZ-treated male C57BL/6J mice (148.4 ± 3.2 mg/dl in untreated controls). Aortic productions of NO•and O2•-were measured specifically and sensitively using electron spin resonance. Diabetic mice had a marked increase in aortic O2•-production. Aortic hydrogen peroxide (H2O2) production was also increased in diabetic aortas and significantly attenuated by AG. AG however had only a marginal effect in reducing aortic O2•-production, which corresponded to a minimal effect in improving aortic nitric oxide (NO•) bioavailability. The endothelium-dependent vasodilatation however was modestly but significantly improved by AG, likely consequent to AG-induced reduction in hyper-contractility.NAD(P)Hoxidase (NOX)-dependent O2•-production was completely attenuated by AG in endothelium-denuded diabetic aortas.

Conclusion

In summary, despite that AG is not an effective eNOS recoupling agent presumably consequent to its ineffectiveness in preventing endothelial NOX activation, it is inhibitory of aortic H2O2production, VSMC NOX activity, and hypercontractility in diabetes.
Tuning microbial hosts for membrane protein production
Authors: Freigassner Maria , Pichler Harald , Glieder Anton
Published: December 2009

The last four years have brought exciting progress in membrane protein research. Finally those many efforts that have been put into expression of eukaryotic membrane proteins are coming to fruition and enable to solve an ever-growing number of high resolution structures. In the past, many skilful optimization steps were required to achieve sufficient expression of functional membrane proteins. Optimization was performed individually for every membrane protein, but provided insight about commonly encountered bottlenecks and, more importantly, general guidelines how to alleviate cellular limitations during microbial membrane protein expression. Lately, system-wide analyses are emerging as powerful means to decipher cellular bottlenecks during heterologous protein production and their use in microbial membrane protein expression has grown in popularity during the past months.

This review covers the most prominent solutions and pitfalls in expression of eukaryotic membrane proteins using microbial hosts (prokaryotes, yeasts), highlights skilful applications of our basic understanding to improve membrane protein production. Omics technologies provide new concepts to engineer microbial hosts for membrane protein production.
Effects of hydrogen sulfide on inflammation in caerulein-induced acute pancreatitis
Authors: Sidhapuriwala Jenab N , Ng Siaw Wei , Bhatia Madhav
Published: December 2009

Background

Hydrogen sulfide (H2S), a gaseous mediator plays an important role in a wide range of physiological and pathological processes. H2S has been extensively studied for its various roles in cardiovascular and neurological disorders. However, the role of H2S in inflammation is still controversial. The current study was aimed to investigate the therapeutic potential of sodium hydrosulfide (NaHS), an H2S donor in in vivo model of acute pancreatitis in mice.

Methods

Acute pancreatitis was induced in mice by hourly caerulein injections (50 μg/kg) for 10 hours. Mice were treated with different dosages of NaHS (5 mg/kg, 10 mg/kg or 15 mg/kg) or with vehicle, distilled water (DW). NaHS or DW was administered 1 h before induction of pancreatitis. Mice were sacrificed 1 h after the last caerulein injection. Blood, pancreas and lung tissues were collected and were processed to measure the plasma amylase, myeloperoxidase (MPO) activities in pancreas and lung and chemokines and adhesion molecules in pancreas and lung.

Results

It was revealed that significant reduction of inflammation, both in pancreas and lung was associated with NaHS 10 mg/kg. Further the anti-inflammatory effects of NaHS 10 mg/kg were associated with reduction of pancreatic and pulmonary inflammatory chemokines and adhesion molecules. NaHS 5 mg/kg did not cause significant improvement on inflammation in pancreas and associated lung injury and NaHS 15 mg/kg did not further enhance the beneficial effects seen with NaHS 10 mg/kg.

Conclusion

In conclusion, these data provide evidence for anti-inflammatory effects of H2S based on its dosage used.
Tyrosine Phosphorylation of the N-Methyl-D-Aspartate Receptor 2B Subunit in Spinal Cord Contributes to Remifentanil-Induced Postoperative Hyperalgesia: the Preventive Effect of Ketamine
Authors: Gu Xiaoping , Wu Xiaoli , Liu Yue , Cui Songqin , Ma Zhengliang
Published: December 2009

Background

Experimental and clinical studies showed that intraoperative infusionof remifentanil has been associated with postoperative hyperalgesia. Previous reports suggested that spinal N-methyl-D-aspartate (NMDA) receptors may contribute to the development and maintenance of opioid-induced hyperalgesia. In the present study, we used a rat model of postoperative pain to investigate the role of tyrosine phosphorylation of NMDA receptor 2B (NR2B) subunit in spinal cord in the postoperative hyperalgesia induced by remifentanil and the intervention of pretreatment with ketamine.

Results

Intraoperative infusion of remifentanil (0.04 mg/kg, subcutaneous) significantly enhanced mechanical allodynia and thermal hyperalgesia induced by the plantar incision during the postoperative period (each lasting between 2 h and 48 h), which was attenuated by pretreatment with ketamine (10 mg/kg, subcutaneous). Correlated with the pain behavior changes, immunocytochemical and western blotting experiments in our study revealed that there was a marked increase in NR2B phosphorylation at Tyr1472 in the superficial dorsal horn after intraoperative infusion of remifentanil, which was attenuated by pretreatment with ketamine.

Conclusions

This study provides direct evidence that tyrosine phosphorylation of the NR2B at Tyr1472 in spinal dosal horn contributes to postoperative hyperalgesia induced by remifentanil and supports the potential therapeutic value of ketamine for improving postoperative hyperalgesia induced by remifentanil.
Cancer patients' attitudes towards Chinese medicine: a Hong Kong survey
Authors: Lam Yuen-chi , Cheng Chung-wah , Peng Heng , Law Chun-key , Huang Xianzhang , Bian Zhaoxiang
Published: December 2009

Background

This article reports a survey conducted in Hong Kong on the cancer patients' attitudes towards Chinese medicine treatment.

Methods

Cancer patients from three Chinese medicine clinics and one oncology clinic were interviewed with a structured questionnaire.

Results

Of a total of 786 participants included in the study, 42.9% used Western medicine only; 57.1% used at least one form of Chinese medicine; 5 participants used Chinese medicine only; and 56.5% used Chinese medicine before/during/after Western medicine treatment. Commonly used Western medicine and Chinese medicine treatments included chemotherapy (63.7%), radiotherapy (62.0%), surgery (57.6%), Chinese herbal medicine (53.9%) and Chinese dietary therapy (9.5%). Participants receiving chemotherapy used Chinese medicine (63.3%) more than those receiving any other Western medicine treatments. Spearman correlation coefficients showed that the selection of Chinese medicine was associated with the cancer type (rs = -1.36; P < 0.001), stage (rs = 0.178; P < 0.001), duration (rs = -0.074; P = 0.037), whether receiving chemotherapy (rs = 0.165; P < 0.001) and palliative therapy (rs = 0.087; P = 0.015). Nearly two-thirds of the participants (N = 274) did not tell their physicians about using Chinese medicine. Over two-thirds of all participants (68.2%) believed that integrated Chinese and Western medicine was effective.

Conclusion

Chinese medicine is commonly used among Hong Kong cancer patients. The interviewed cancer patients in Hong Kong considered integrative Chinese and Western medicine is an effective cancer treatment.
Transplantation and innate immunity: the lesson of natural killer cells
Authors: Bertaina Alice , Locatelli Franco , Moretta Lorenzo
Published: December 2009

Natural killer cells have been demonstrated to play a major role in mediating an anti-leukemia effect in patients given a T-cell depleted allogeneic hematopoietic stem cell transplantation from an HLA-haploidentical family donor. In particular, donor-derived natural killer cells, which are alloreactive (i.e. KIR/HLA mismatched) towards recipient cells, significantly contribute to the eradication of leukemia blasts escaping the preparative regimen to transplantation. A recent study on high-risk pediatric acute lymphoblastic leukemia refractory to chemotherapy further highlighted the importance of donors with alloreactive natural killer cells in haploidentical hematopoietic stem cell transplantation, as it demonstrated that these cells can emerge starting from the fourth-fifth month after the allograft and persist for many months. This study represents a major breakthrough in the cure of otherwise fatal leukemias, providing information on the best criteria for choosing the optimal donor.
Correlating measurements across samples improves accuracy of large-scale expression profile experiments
Authors: Alvarez Mariano Javier , Sumazin Pavel , Rajbhandari Presha , Califano Andrea
Published: December 2009

Gene expression profiling technologies suffer from poor reproducibility across replicate experiments. However, when analyzing large datasets, probe-level expression profile correlation can help identify flawed probes and lead to the construction of truer probe sets with improved reproducibility. We describe methods to eliminate uninformative and flawed probes, account for dependence between probes, and address variability due to transcript-isoform mixtures. We test and validate our approach on Affymetrix microarrays and outline their future adaptation to other technologies.
Mottle camouflage patterns in cuttlefish: quantitative characterization and visual background stimuli that evoke them
Authors: Chiao Chuan-Chin , Chubb Charles , Buresch Kendra C. , Barbosa Alexandra , Allen Justine J. , Mäthger Lydia M. , Hanlon Roger T.
Published: December 2009

Cuttlefish and other cephalopods achieve dynamic background matching with two general classes of body patterns: uniform (or uniformly stippled) patterns and mottle patterns. Both pattern types have been described chiefly by the size scale and contrast of their skin components. Mottle body patterns in cephalopods have been characterized previously as small-to-moderate-scale light and dark skin patches (i.e. mottles) distributed somewhat evenly across the body surface. Here we move beyond this commonly accepted qualitative description by quantitatively measuring the scale and contrast of mottled skin components and relating these statistics to specific visual background stimuli (psychophysics approach) that evoke this type of background-matching pattern. Cuttlefish were tested on artificial and natural substrates to experimentally determine some primary visual background cues that evoke mottle patterns. Randomly distributed small-scale light and dark objects (or with some repetition of small-scale shapes/sizes) on a lighter substrate with moderate contrast are essential visual cues to elicit mottle camouflage patterns in cuttlefish. Lowering the mean luminance of the substrate without changing its spatial properties can modulate the mottle pattern toward disruptive patterns, which are of larger scale, different shape and higher contrast. Backgrounds throughout nature consist of a continuous range of spatial scales; backgrounds with medium-sized light/dark patches of moderate contrast are those in which cuttlefish Mottle patterns appear to be the most frequently observed.
Acute kidney injury: how do we define it?
Authors: Lewington Andrew J P , Sayed Ahmed
Published: December 2009

Over recent years, there has been welcome increased interest in acute kidney injury (AKI) and its association with patient outcome. The term AKI has replaced the term acute renal failure (ARF) and encompasses all types of ARF. New definitions and staging systems for AKI have been proposed, which have stimulated a multitude of different studies to evaluate their clinical utility. These recent advances need to be communicated to the wider health care community so that we are using a shared nomenclature. In 2009 the National Confidential Enquiry into Patient Outcome and Death AKI study (‘Adding Insult to Injury’) announced its findings and recommendations. The report recommended that the detection of AKI and its management should be improved. These recommendations along with the adoption of the new staging systems will potentially have an impact on clinical biochemistry departments and exert an increased demand on resources. Running in parallel with these initiatives is the quest to discover novel biomarkers to detect AKI, the development and introduction of which will require laboratory support.
Application of housekeeping npcRNAs for quantitative expression analysis of human transcriptome by real-time PCR
Authors: Galiveti Chenna R. , Rozhdestvensky Timofey S. , Brosius Jürgen , Lehrach Hans , Konthur Zoltán
Published: December 2009

In recent years the improvements in high-throughput gene expression analysis have led to the discovery of numerous non-protein-coding RNA (npcRNA) molecules. They form an abundant class of untranslated RNAs that have shown to play a crucial role in different biochemical pathways in the cell. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is an efficient tool to measure RNA abundance and gene expression levels in tiny amounts of material. Despite its sensitivity, the lack of appropriate internal controls necessary for accurate data analysis is a limiting factor for its application in npcRNA research. Common internal controls applied are protein-coding reference genes, also termed “housekeeping” genes (HKGs). However, their expression levels reportedly vary among tissues and different experimental conditions. Moreover, application of HKGs as reference in npcRNA expression analyses is questionable, due to the differences in biogenesis. To address the issue of optimal RT-qPCR normalizers in npcRNA analysis, we performed a systematic evaluation of 18 npcRNAs along with four common HKGs in 20 different human tissues. To determine the most suitable internal control with least expression variance, four evaluation strategies, geNORM, NormFinder, BestKeeper, and the comparative delta Cq method, were applied. Our data strongly suggest that five npcRNAs, which we term housekeeping RNAs (HKRs), exhibit significantly better constitutive expression levels in 20 different human tissues than common HKGs. Determined HKRs are ideal candidates for RT-qPCR data normalization in human transcriptome analysis, and might also be used as reference genes irrespective of the nature of the genes under investigation.
Preferential translation of Hsp83 in Leishmania requires a thermosensitive polypyrimidine-rich element in the 3′ UTR and involves scanning of the 5′ UTR
Authors: David Maya , Gabdank Idan , Ben-David Miriam , Zilka Alon , Orr Irit , Barash Danny , Shapira Michal
Published: December 2009

Heat shock proteins (HSPs) provide a useful system for studying developmental patterns in the digenetic Leishmania parasites, since their expression is induced in the mammalian life form. Translation regulation plays a key role in control of protein coding genes in trypanosomatids, and is directed exclusively by elements in the 3′ untranslated region (UTR). Using sequential deletions of the Leishmania Hsp83 3′ UTR (888 nucleotides [nt]), we mapped a region of 150 nt that was required, but not sufficient for preferential translation of a reporter gene at mammalian-like temperatures, suggesting that changes in RNA structure could be involved. An advanced bioinformatics package for prediction of RNA folding (UNAfold) marked the regulatory region on a highly probable structural arm that includes a polypyrimidine tract (PPT). Mutagenesis of this PPT abrogated completely preferential translation of the fused reporter gene. Furthermore, temperature elevation caused the regulatory region to melt more extensively than the same region that lacked the PPT. We propose that at elevated temperatures the regulatory element in the 3′ UTR is more accessible to mediators that promote its interaction with the basal translation components at the 5′ end during mRNA circularization. Translation initiation of Hsp83 at all temperatures appears to proceed via scanning of the 5′ UTR, since a hairpin structure abolishes expression of a fused reporter gene.
Accuracy Certificates for Computational Problems with Convex Structure
Authors: Nemirovski Arkadi , Onn Shmuel , Rothblum Uriel G.
Published: December 2009

The goal of this paper is to introduce the notion of certificates, which verify the accuracy of solutions of computational problems with convex structure. Such problems include minimizing convex functions, variational inequalities with monotone operators, computing saddle points of convex-concave functions, and solving convex Nash equilibrium problems. We demonstrate how the implementation of the ellipsoid method and other cutting plane algorithms can be augmented with the computation of such certificates without significant increase of the computational effort. Further, we show that (computable) certificates exist for any algorithm that is capable of producing solutions of guaranteed accuracy.
Cooperation in Service Systems
Authors: Anily Shoshana , Haviv Moshe
Published: December 2009

We consider a number of servers that may improve the efficiency of the system by pooling their service capacities to serve the union of the individual streams of customers. This economies-of-scope phenomenon is due to the reduction in the steady-state mean total number of customers in the system. The question we pose is how the servers should split among themselves the cost of the pooled system. When the individual incoming streams of customers form Poisson processes and individual service times are exponential, we define a transferable utility cooperative game in which the cost of a coalition is the mean number of customers (or jobs) in the pooled system. We show that, despite the characteristic function is neither monotone nor concave, the game and its subgames possess nonempty cores. In other words, for any subset of servers there exist cost-sharing allocations under which no partial subset can take advantage by breaking away and forming a separate coalition. We give an explicit expression for all (infinitely many) nonnegative core cost allocations of this game. Finally, we show that, except for the case where all individual servers have the same cost, there exist infinitely many core allocations with negative entries, and we show how to construct a convex subset of the core where at least one server is being paid to join the grand coalition.
Robust Approximation to Multiperiod Inventory Management
Authors: See Chuen-Teck , Sim Melvyn
Published: December 2009

We propose a robust optimization approach to address a multiperiod inventory control problem under ambiguous demands, that is, only limited information of the demand distributions such as mean, support, and some measures of deviations. Our framework extends to correlated demands and is developed around a factor-based model, which has the ability to incorporate business factors as well as time-series forecast effects of trend, seasonality, and cyclic variations. We can obtain the parameters of the replenishment policies by solving a tractable deterministic optimization problem in the form of a second-order cone optimization problem (SOCP), with solution time; unlike dynamic programming approaches, it is polynomial and independent on parameters such as replenishment lead time, demand variability, and correlations. The proposed truncated linear replenishment policy (TLRP), which is piecewise linear with respect to demand history, improves upon static and linear policies, and achieves objective values that are reasonably close to optimal.
A Shadow Simplex Method for Infinite Linear Programs
Authors: Ghate Archis , Sharma Dushyant , Smith Robert L.
Published: December 2009

We present a simplex-type algorithm—that is, an algorithm that moves from one extreme point of the infinite-dimensional feasible region to another, not necessarily adjacent, extreme point—for solving a class of linear programs with countably infinite variables and constraints. Each iteration of this method can be implemented in finite time, whereas the solution values converge to the optimal value as the number of iterations increases. This simplex-type algorithm moves to an adjacent extreme point and hence reduces to a true infinite-dimensional simplex method for the important special cases of nonstationary infinite-horizon deterministic and stochastic dynamic programs.
Safety Considerations and Potential Interactions of Vitamins: Should Vitamins Be Considered Drugs?
Authors: Rogovik Alexander L , Vohra Sunita , Goldman Ran D
Published: December 2009

Objective:

To examine adverse effects, adverse events, and potential interactions of vitamins in light of their current prevalence of use, and to discuss whether vitamins should be considered over-the-counter drugs or natural health products/dietary supplements.

Data Sources:

We performed a MEDLINE/PubMed search, explored 4 online databases (Medline Plus, Drug Digest, Natural Medicine Comprehensive Database, and the database of the University of Maryland), and examined reference lists of inclucted studies published from 1966 through October 2009.

Study Selection and Data Extraction:

The studies were reviewed, with an emphasis on randomized controlled clinical trials. We included articles with the most clinically important information with regard to adverse events and interactions.

Data Synthesis:

Vitamins are used by over one third of the North American population. Vitamins have documented adverse effects and toxicities, and most have documented interactions with drugs. While some vitamins (biotin, pantothenic acid, riboflavin, thiamine, vitamin B12, vitamin K) have minor and reversible adverse effects, others, such as fat-soluble vitamins (A, E, D), can cause serious adverse events. Two water-soluble vitamins, folic acid and niacin, can also have significant toxicities and adverse events.

Conclusions:

Our recommendation is that vitamins A, E, D, folic acid, and niacin should be categorized as over-the-counter medications. Labeling of vitamins, especially those intended for children and other vulnerable groups, should include information on possible toxicities, dosing, recommended upper intake limits, and concurrent use with other products. Vitamin A should be excluded from multivitamin supplements and food fortificants.
Integrase Inhibitors: A Novel Class of Antiretroviral Agents
Authors: Schafer Jason J , Squires Kathleen E
Published: December 2009

OBJECTIVE

To review the pharmacology, efficacy, safety, and resistance profiles of the integrase inhibitors raltegravir and elvitegravir.

DATA SOURCES

A search of PubMed was conducted (2000-August 2009) using the following key words: raltegravir, MK-0518, elvitegravir, and GS-9137. Articles were evaluated for content and bibliographies were reviewed. Data available exclusively in abstracts from major infectious diseases and HIV conferences were also evaluated for inclusion.

STUDY SELECTION AND DATA EXTRACTION

Studies included were in vitro investigations; Phase 1, 2, and 3 clinical trials; retrospective analyses including case reports; and pharmacokinetic and pharmacodynamic evaluations.

DATA SYNTHESIS

Raltegravir is currently approved by the Food and Drug Administration for the management of HIV-1 infection in treatment-naïve or -experienced adults as part of an optimized combination regimen. When combined with other active agents, it has demonstrated similar virologic efficacy after 96 weeks to the combination of efavirenz, tenofovir, and emtricitabine in treatment-naïve patients. Unlike many antiretrovirals, raltegravir does not enter cytochrome P450 metabolism and instead undergoes glucuronidation. Elvitegravir is in the late stages of clinical development. A Phase 2 study has demonstrated virologic efficacy in treatment-experienced patients comparable to protease inhibitor-based regimens after 24 weeks. Boosting of elvitegravir through inhibition of CYP3A4 metabolism has been investigated and suggests a pharmacokinetic profile conducive to once-daily-dosing. Phase 2 and 3 clinical trials evaluating boosted elvitegravir are in process. The Phase 2 trial combines elvitegravir with a non-ritonavir boosting agent plus tenofovir/emtricitabine given once daily as a “quad-pill” formulation. The Phase 3 trial compares once-daily ritonavir-boosted elvitegravir with twice-daily raltegravir, each given with an optimized background regimen. Both integrase inhibitors are well tolerated and raltegravir has few drug-drug interactions. Resistance mutations have been identified in patients experiencing virologic failure and cross resistance between raltegravir and elvitegravir has been confirmed.

CONCLUSIONS

The integrase inhibitors provide a novel target for antiretroviral therapy and provide an option for patients harboring resistance to other antiretrovirals.
Fluconazole Prophylaxis in High-Risk Neonates
Authors: Reed Brent N , Caudle Kelly E , Rogers P David
Published: December 2009

OBJECTIVE

To evaluate the literature regarding the use of fluconazole prophylaxis in high-risk neonates.

DATA SOURCES

Literature was accessed through MEDLINE (February 2001-August 2009) using the search terms fluconazole and prophylaxis, with limits for age group (ie, birth-18 y). Reference citations from identified articles were also reviewed.

DATA SELECTION AND DATA EXTRACTION

All prospective and retrospective studies in English identified from MEDLINE were evaluated.

DATA SYNTHESIS

Critically ill neonates possess a number of risk factors that predispose them to fungal colonization with Candida spp. In many cases, colonization may progress to invasive systemic infections despite efforts aimed at early diagnosis and treatment. Because of its success among immunocompromised patients, fluconazole prophylaxis has been suggested as a possible approach for reducing the rates of both colonization and invasive fungal infections among at-risk neonates. To date, 4 prospective randomized controlled trials and 8 retrospective cohort studies have examined fluconazole prophylaxis in neonates. Although fluconazole prophylaxis appears to reduce the rates of colonization and invasive fungal infections, no trial in this review was able to demonstrate a significant difference in long-term morbidity or mortality. Concerns also remain regarding the adverse effects associated with prolonged exposure to fluconazole therapy. Lack of standardized study designs and treatment regimens also limit widespread recommendation for the use of fluconazole prophylaxis in clinical practice.

CONCLUSIONS

While it may be beneficial for critically ill neonates with certain predisposing risk factors (eg, central venous access, sustained exposure to broad-spectrum antibiotics, or units with significantly high incidence of invasive fungal infections), existing research does not support the use of fluconazole prophylaxis based on birth weight or gestational age alone. Multifactor analysis evaluating the effect of fluconazole prophylaxis is necessary to establish which neonates would benefit from this practice.
Black Box Warning Contraindicated Comedications: Concordance Among Three Major Drug Interaction Screening Programs
Authors: Wang Lorraine M , Wong Maple , Lightwood James M , Cheng Christine M
Published: December 2009

BACKGROUND

Black box warnings represent the strongest safety warning that the Food and Drug Administration can issue for a marketed prescription drug. Some black box warnings recommend against coadministration of specific medications due to an increased risk for serious, perhaps life-threatening, effects.

OBJECTIVE

To determine the level of agreement in presence, clinical severity scores level of documentation ratings, and alert content among 3 leading drug interaction screening programs with regard to contraindicated comedications that are mentioned in black box warnings.

METHODS

We reviewed the prescribing information for currently marketed prescription drugs with a black box warning that mentioned a contraindicated drug combination. We selected the drug interaction databases Facts & Comparisons 4.0, MICROMEDEX DRUG-REAX, and Lexi-Comp Lexi-Interact to evaluate the interactions. Discrepancies in the inclusion of interactions and level of agreement in clinical severity scores and level of documentation ratings for each interaction were assessed, using descriptive statistics, Spearman's correlation coefficient, Kendall-Stuart Ö-c, and Cronbach's α.

RESULTS

We identified 11 drugs with black box warnings that contained information on 59 unique contraindicated drug combinations, only 68% of which were covered by any source. Lexi-Comp detected the most interactions (n = 29) and DRUG-REAX the least (n = 18). Only 3 drug combinations were detected and rated as contraindicated or potentially life-threatening in all 3 databases. The severity scores and level of documentation ratings varied widely.

CONCLUSIONS

There are discrepancies among major drug interaction screening programs in the inclusion, severity, and level of documentation of contraindicated drug combinations mentioned in black box warnings. Further studies could explore the implications of these inconsistencies, particularly with regard to the integration of black box warning information in clinical practice. Clinicians should consult multiple drug resources to maximize the potential for detecting a potentially severe drug interaction.
Implementation of a Closed-Loop Reporting System for Critical Values and Clinical Communication in Compliance with Goals of The Joint Commission
Authors: Parl Fritz F , O'Leary Mandy F , Kaiser Allen B , Paulett John M , Statnikova Kristina , Shultz Edward K
Published: December 2009

Background: Current practices of reporting critical laboratory values make it challenging to measure and assess the timeliness of receipt by the treating physician as required by The Joint Commission’s 2008 National Patient Safety Goals.

Methods: A multidisciplinary team of laboratorians, clinicians, and information technology experts developed an electronic ALERTS system that reports critical values via the laboratory and hospital information systems to alphanumeric pagers of clinicians and ensures failsafe notification, instant documentation, automatic tracking, escalation, and reporting of critical value alerts. A method for automated acknowledgment of message receipt was incorporated into the system design.

Results: The ALERTS system has been applied to inpatients and eliminated approximately 9000 phone calls a year made by medical technologists. Although a small number of phone calls were still made as a result of pages not acknowledged by clinicians within 10 min, they were made by telephone operators, who either contacted the same physician who was initially paged by the automated system or identified and contacted alternate physicians or the patient’s nurse. Overall, documentation of physician acknowledgment of receipt in the electronic medical record increased to 95% of critical values over 9 months, while the median time decreased to <3 min.

Conclusions: We improved laboratory efficiency and physician communication by developing an electronic system for reporting of critical values that is in compliance with The Joint Commission’s goals.
Latrodectism in New Caledonia: First Report of Presumed Redback Spider (Latrodectus hasselti) Envenomation
Authors: Maillaud Claude , Jourdan Hervé , Winkel Ken , Arnaud Gaëlle , Lafforgue Patrick , Durand Francis
Published: December 2009

We describe a recent case of presumed redback spider ( Latrodectus hasselti) envenomation observed near Noumea in New Caledonia. This is the first local reported case in this archipelago, where L. hasselti is currently considered a native species. We highlight the challenge of providing appropriate analgesia in this situation and believe that the use of specific redback spider antivenom should be considered in New Caledonia.
The South Millevaches Middle Carboniferous crustal melting and its place in the French Variscan belt
Authors: Faure Michel , Mezeme Eugène Be , Cocherie Alain , Melleton Jérémie , Rossi Philippe
Published: December 2009

Several episodes of crustal melting are now well identified in the Variscan French Massif Central. Middle Devonian (ca 385-375 Ma) migmatites are recognized in the Upper and Lower Gneiss Units involved in the stack of nappes. Late Carboniferous migmatites (ca 300 Ma) are exposed in the Velay Massif only and Middle Carboniferous migmatites crop out in the Para-autochthonous Unit and southern Fold-and-Thrust Belt. In the SW part of the Massif Central, the South Millevaches massif exposes migmatites developed at the expense of ortho- and paragneiss. They form kilometer-sized septa within the foliated Goulles leucogranitic pluton, which is in turn intruded by the non-foliated Glény two micas granite pluton. Monazite grains extracted from these three rock-types have been dated by the EPMA chemical method. Three samples of migmatite yield a late Visean age (ca 337-328 Ma), the Goulles and Glény granitic plutons yield ages at 324-323 Ma and 324-318 Ma, respectively. These new results enlarge the evidence of a Middle Carboniferous crustal melting imprint that up to now was only reported in the eastern part of the French Massif Central, in the northern Cévennes and in the Montagne Noire axial zone. At the scale of the French Variscan massifs, the Visean crustal melting event is conspicuously developed since it is recognized from the Massif Armoricain (Vendée and south coast of Brittany) to the Central Vosges. This episode is synchronous with the huge thermal event responsible for the “Tuffs anthracifères” magmatism of the northern Massif Central and Vosges, and took place immediately after the last thickening phase recorded both in Montagne Noire and Ardennes, that is on the southern and northern outer zones of the Variscan Belt, respectively. However, the geodynamic significance of this major event is not fully understood yet.
Age and depositional environment of the Sainte-Anne Formation (Armorican Massif, France): the oldest (Emsian) evidence for mountain erosion in the Variscan belt
Authors: Ducassou Céline , Strullu-Derrien Christine , Ballevre Michel , Dabard Marie-Pierre , Gerrienne Philippe , Lardeux Hubert , Robin Cécile
Published: December 2009

The palaeogeography of the internal zones of the Variscan belt during the early stages of the convergence remains unclear. Sedimentary sequences that recorded the denudation of an early relief have generally been removed by erosion. In the Chalonnes area (southeast of the Armorican Massif), the reefal carbonates of the Chalonnes Formation (Fm) are overlain by the immature, poorly-sorted sandstones of the Sainte-Anne Fm. This formation is characterised by the occurrence of gravity flow deposits and contains immature and poorly sorted sandstones with a large amount of plant debris and lithic fragments, suggesting a depositional environment in a delta front dominated by floods. A revision of the palaeoflora content allows to assign an Emsian age to the Sainte-Anne Fm. Lithic fragments are mainly of sedimentary and volcanic origin, suggesting moderate erosion level of the source area. Palaeocurrent data indicate a southern origin for the sediments. These features collectively demonstrate that the Sainte-Anne Fm is the record of the erosion of a continental area located farther south, and experiencing incipient tectonic uplift during the Emsian. The Sainte-Anne Fm could represent therefore the earliest record in France of the very first stages of the Variscan orogeny.