bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory of own mind in autism
Authors: Williams David
Published: October 2010

Assuming that self-awareness is not a unitary phenomenon, and that one can be aware of different aspects of self at any one time, it follows that selective impairments in self-awareness can occur. This article explores the idea that autism involves a particular deficit in awareness of the ‘psychological self’, or ‘theory of own mind’. This hypothesised deficit renders individuals with autism spectrum disorder (ASD) at least as impaired at recognising their own mental states as at recognising mental states in other people. This deficit, it is argued, stands in contrast to an apparently typical awareness of the ‘physical self’ amongst people with autism. Theoretical implications of the empirical evidence are discussed.
Effects of Prescribed Medications on Cognition and Behavior in Frontotemporal Lobar Degeneration
Authors: Irwin David , Lippa Carol F. , Rosso Andrea
Published: October 2010

A retrospective chart review of 21 patients meeting core clinical criteria for behavioral or aphasic variants of frontotemporal lobar degeneration (FTLD) was conducted. Data recorded included Folstein Mini-Mental State Examination (MMSE) scores, medications prescribed, and subjective reports of behavioral symptoms from each visit. Behaviors were graded on a scale from 1 to 3 and totaled for each visit. Changes in MMSE and behavior scores between visits 1 month and 6 months apart where a new medication was started were analyzed using a paired t test and were compared between medication classes using an unpaired t test. Acetylcholinesterase inhibitors (AChEIs) were associated with a decrease in MMSE scores by 1.6 (P = .02) and an increase in total behavior scores by 1.0 (P = .03). Mean MMSE and behavior scores were statistically more improved by selective serotonin reuptake inhibitors than AChEIs (P = .04). This data suggest a potential worsening of objective measures of cognitive and behavioral symptoms in FTLD with AChEI treatment.
Assessing Specific Grapho-Phonemic Skills in Elementary Students
Authors: Robbins Kelly P. , Hosp John L. , Hosp Michelle K. , Flynn Lindsay J.
Published: October 2010

This study examines the relation between decoding and spelling performance on tasks that represent identical specific grapho-phonemic patterns. Elementary students ( N = 206) were administered a 597 pseudoword decoding inventory representing 12 specific grapho-phonemic patterns and a 104 real-word spelling inventory representing identical grapho-phonemic patterns presented on the decoding inventory. Correlational and quantile regression analyses revealed a moderate to strong correlation between student performance in decoding and spelling tasks, with stronger relations found among more complex grapho-phonemic patterns and weaker relations found among less complex grapho-phonemic patterns. The results of this study support the utility of a spelling assessment with items representing a wide range of grapho-phonemic patterns as a screener for specific areas of grapho-phonemic knowledge weakness and provide educators with an efficient method of collecting the data needed to develop targeted interventions.
Leading Systemic Improvement: Confronting Complexity in Turnaround Schools
Authors: Peurach Donald J. , Marx Gary E.
Published: October 2010

This case is developed for use in a policy-centered course on systemic improvement in underperforming districts and schools. The narrative details the complexity that arose in the context of one such reform initiative, a framework for analyzing that complexity, and a set of leadership decisions that follow. Course instructors can use the case to: motivate students’ interest in district-driven systemic improvement, examine issues that often complicate such work, review emerging research on school turnaround efforts, and frame further inquiry into actual cases of district-driven systemic improvement.
The adult day care workforce in England at a time of policy change: implications for learning disability support services
Authors: Hussein Shereen , Manthorpe Jill
Published: October 2010

More people will receive personal budgets to pay for social care services in England. Such people may or may not continue using services such as adult day care centres. Many day centres are under threat of closure. These trends will affect those working in adult day care. This article examines the profile of this workforce, using recent NMDS-SC data and applying multinomial statistical modelling. We identified nearly 6000 adult day care workers, over half supporting adults with learning disability. The results of the analysis show significant variations between the adult day care, residential care and domiciliary workforces. At the personal level, day care workers are significantly older and less ethnically diverse than other workers. They tend to have been working in the sector for longer, and their work patterns are more stable. The findings are discussed within the context of policy changes affecting learning disabilities and social care workforce strategies.
Antenatal testing and the subsequent birth of a child with Down syndrome: a phenomenological study of parents’ experiences
Authors: Sooben Roja D.
Published: October 2010

The objective was to gain a deeper insight into the lived experiences of parents during antenatal testing for Down syndrome and the subsequent birth of their baby. A phenomenological research inquiry used unstructured interviews and thematic framework analysis. Conversations between parents and midwives about Down syndrome, when they occurred, were brief, functional and had a biomedical problem orientation. Antenatal screening failed to meet parents’ expectations of better preparation for birth. After birth, children’s ‘differentness’ rather than health needs was the main focus of care interventions. The inquiry revealed the ‘invisibility’ of the potential child with Down syndrome. Professionals in maternity care services must be equipped with appropriate knowledge about Down syndrome in order to better support parents. Such preparation must include a balanced view of the future of the child, consistent with the principle of reproductive autonomy. Appropriate support after birth is also essential in helping parents to adapt to their new situation.
Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments
Authors: Stolk Jan , Cooper Brendan G. , Stoel Berend , Rames Alexis , Rutman Olga , Soliman Sherif , Stockley Robert
Published: October 2010

Emphysema is characterized by the destruction of alveolar wall and enlargement of alveolar airspaces, resulting in a reduction of the total lung gas exchange area, loss of lung elastic recoil and hyperinflation. The REPAIR study (Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry) is the first proof-of-concept study of a new potential disease-modifying drug, Palovarotene©, an orally active, gamma selective retinoid agonist in patients with emphysema secondary to alpha-1-antitrypsin deficiency (AATD) as a model population for the general smoke-induced emphysema population. This article describes the study design as well as the effectiveness of the quality control that was implemented on the key efficacy endpoints, based on data derived from the placebo-treated subjects. In this multicentre, multinational study the implementation of standardized procedures included: careful site selection, use of trained staff, regular monitoring and machine calibration, use of biological controls and regular feedback to sites by an independent quality control centre. All of these procedures resulted in high-quality measurements of lung density, spirometry, static lung volumes and gas transfer. It was also confirmed that CT lung density was the most sensitive endpoint followed by TLco, FEV1 and RV measured by body box.
Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning
Authors: Majhail Navneet S. , Brazauskas Ruta , Rizzo J. Douglas , Sobecks Ronald M. , Wang Zhiwei , Horowitz Mary M. , Bolwell Brian , Wingard John R. , Socie Gerard
Published: October 2010

Risks of secondary solid cancers among allogeneic hematopoietic cell transplant (HCT) recipients who receive conditioning without total body irradiation are not well known. We evaluated the incidence and risk factors for solid cancers after HCT using high-dose busulfan-cyclophosphamide conditioning in 4318 recipients of first allogeneic HCT for acute myeloid leukemia in first complete remission (N = 1742) and chronic myeloid leukemia in first chronic phase (N = 2576). Our cohort represented 22 041 person-years at risk. Sixty-six solid cancers were reported at a median of 6 years after HCT. The cumulative-incidence of solid cancers at 5 and 10 years after HCT was 0.6% and 1.2% among acute myeloid leukemia and 0.9% and 2.4% among chronic myeloid leukemia patients. In comparison to general population incidence rates, HCT recipients had 1.4× higher than expected rate of invasive solid cancers (95% confidence interval, 1.08-1.79, P = .01). Significantly elevated risks were observed for tumors of the oral cavity, esophagus, lung, soft tissue, and brain. Chronic graft-versus-host disease was an independent risk factor for all solid cancers, and especially cancers of the oral cavity. Recipients of allogeneic HCT using busulfan-cyclophosphamide conditioning are at risk for developing solid cancers. Their incidence continues to increase with time, and lifelong cancer surveillance is warranted in this population.
Differential functional genomic effects of anti-inflammatory phytocompounds on immune signaling
Authors: Chiu Shao-Chih , Tsao Shan-Wen , Hwang Pei-Ing , Vanisree Staniforth , Chen Yi-An , Yang Ning-Sun
Published: October 2010

Background

Functional comparative genomic analysis of the cellular immunological effects of different anti-inflammatory phytocompounds is considered as a helpful approach to distinguish the complex and specific bioactivities of candidate phytomedicines. Using LPS-stimulated THP-1 monocytes, we characterize here the immunomodulatory activities of three single phytocompounds (emodin, shikonin, and cytopiloyne) and a defined phytocompound mixture extracted fromEchinaceaplant (BF/S+L/Ep) by focused DNA microarray analysis of selected immune-related genes.

Results

Shikonin and emodin significantly inhibited the early expression (within 0.5 h) of approximately 50 genes, notably cytokines TNF-α, IL-1β and IL-4, chemokines CCL4 and CCL8, and inflammatory modulators NFATC3 and PTGS2. In contrast, neither cytopiloyne nor BF/S+L/Ep inhibited the early expression of these 50 genes, but rather inhibited most late-stage expression (~12 h) of another immune gene subset. TRANSPATH database key node analysis identified the extracellular signal-regulated kinase (ERK) 1/2 activation pathway as the putative target of BF/S+L/Ep and cytopiloyne. Western blot confirmed that delayed inactivation of the ERK pathway was indeed demonstrable for these two preparations during the mid-stage (1 to 4 h) of LPS stimulation. We further identified ubiquitin pathway regulators, E6-AP and Rad23A, as possible key regulators for emodin and shikonin, respectively.

Conclusion

The current focused DNA microarray approach rapidly identified important subgenomic differences in the pattern of immune cell-related gene expression in response to specific anti-inflammatory phytocompounds. These molecular targets and deduced networks may be employed as a guide for classifying, monitoring and manipulating the molecular and immunological specificities of different anti-inflammatory phytocompounds in key immune cell systems and for potential pharmacological application.
Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage
Authors: Tulsawani Rajkumar , Kelly Lorena S , Fatma Nigar , Chhunchha Bhavanaben , Kubo Eri , Kumar Anil , Singh Dhirendra P
Published: October 2010

Background

The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS)-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC) death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6) plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis.

Results

We have shown that RGCs exposed to hypoxia (1%) or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM), revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6.

Conclusion

Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.
Comparison of real-time PCR and microscopy for malaria parasite detection in Malawian pregnant women
Authors: Rantala Anne-Maria , Taylor Steve M , Trottman Paul A , Luntamo Mari , Mbewe Bernard , Maleta Kenneth , Kulmala Teija , Ashorn Per , Meshnick Steven R
Published: October 2010

Background

New diagnostic tools for malaria are required owing to the changing epidemiology of malaria, particularly among pregnant women in sub-Saharan Africa. Real-time PCR assays targetingPlasmodium falciparumlactate dehydrogenase (pfldh) gene may facilitate the identification of a high proportion of pregnant women with aP. falciparumparasitaemia below the threshold of microscopy. These molecular methods will enable further studies on the effects of these submicroscopic infections on maternal health and birth outcomes.

Methods

Thepfldhreal-time PCR assay and conventional microscopy were compared for the detection ofP. falciparumfrom dried blood spots and blood smears collected from the peripheral blood of 475 Malawian women at delivery. A cycle threshold (Ct) of the real-time PCR was determined optimizing the sensitivity and specificity of thepfldhPCR assay compared to microscopy. A real-time PCR species-specific assay was applied to identify the contribution to malaria infections of threePlasmodiumspecies (P. falciparum P. ovaleandP. malariae) in 44 discordant smear andpfldhPCR assay results.

Results

Of the 475 women,P. falciparumwas detected in 11 (2.3%) by microscopy and in 51 (10.7%) by real-time PCR; compared to microscopy, the sensitivity of real-time PCR was 90.9% and the specificity 91.2%. If a Ct value of 38 was used as a cut-off, specificity improved to 94.6% with no change in sensitivity. The real-time PCR species-specific assay detectedP. falciparumalone in all but four samples: two samples were mixed infections withP. falciparumandP. malariae, one was a pureP. malariaeinfection and one was apfldhPCR assay-positive/species-specific assay-negative sample. Of threeP. malariaeinfections detected by microscopy, only one was confirmed by the species-specific assay.

Conclusions

Although microscopy remains the most appropriate method for clinical malaria diagnosis in field settings, molecular diagnostics such as real-time PCR offer a more reliable means to detect malaria parasites, particularly at low levels. Determination of the possible contribution of these submicroscopic infections to poor birth outcomes and maternal health is critical. For future studies to investigate these effects, thispfldhreal-time PCR assay offers a reliable detection method.
Proteomic characterization of van A-containing Enterococcu s recovered from Seagulls at the Berlengas Natural Reserve, W Portugal
Authors: Radhouani Hajer , Poeta Patrícia , Pinto Luís , Miranda Júlio , Coelho Céline , Carvalho Carlos , Rodrigues Jorge , López María , Torres Carmen , Vitorino Rui , Domingues Pedro , Igrejas Gilberto
Published: October 2010

Background

Enterococci have emerged as the third most common cause of nosocomial infections, requiring bactericidal antimicrobial therapy. Although vancomycin resistance is a major problem in clinics and has emerged in an important extend in farm animals, few studies have examined it in wild animals. To determine the prevalence of van A-containing Enterococcus strains among faecal samples of Seagulls (Larus cachinnans) of Berlengas Natural Reserve of Portugal, we developed a proteomic approach integrated with genomic data. The purpose was to detect the maximum number of proteins that vary in different enterococci species which are thought to be connected in some, as yet unknown, way to antibiotic resistance.

Results

From the 57 seagull samples, 54 faecal samples showed the presence of Enterococcus isolates (94.7%). For the enterococci, E. faecium was the most prevalent species in seagulls (50%), followed by E. faecalis and E. durans (10.4%), and E. hirae (6.3%). VanA-containing enterococcal strains were detected in 10.5% of the 57 seagull faecal samples studied. Four of the vanA-containing enterococci were identified as E. faecium and two as E. durans. The tet(M) gene was found in all five tetracycline-resistant vanA strains. The erm(B) gene was demonstrated in all six erythromycin-resistant vanA strains. The hyl virulence gene was detected in all four van A-containing E. faecium isolates in this study, and two of them harboured the pur K1 allele. In addition these strains also showed ampicillin and ciprofoxacin resistance. The whole-cell proteomic profile of van A-containing Enterococcus strains was applied to evaluate the discriminatory power of this technique for their identification. The major differences among species-specific profiles were found in the positions corresponding to 97-45 kDa. Sixty individualized protein spots for each vanA isolate was identified and suitable for peptide mass fingerprinting measures by spectrometry measuring (MALDI/TOF MS) and their identification through bioinformatic databases query. The proteins were classified in different groups according to their biological function: protein biosynthesis, ATP synthesis, glycolysis, conjugation and antibiotic resistance. Taking into account the origin of these strains and its relation to infectious processes in humans and animals, it is important to explore the proteome of new strains which might serve as protein biomarkers for biological activity.

Conclusions

The comprehensive description of proteins isolated from vancomycin-resistant Enterococcus faecium and E. durans may provide new targets for development of antimicrobial agents. This knowledge may help to identify new biomarkers of antibiotic resistance and virulence factors.
A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases
Authors: Miller Ira J , Blank Alan , Yin Suellen M , Mcnickle Allison , Gray Robert , Gitelis Steven
Published: October 2010

Giant cell tumor (GCT) of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated sarcomas. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT.
Scoring function to predict solubility mutagenesis
Authors: Tian Ye , Deutsch Christopher , Krishnamoorthy Bala
Published: October 2010

Background

Mutagenesis is commonly used to engineer proteins with desirable properties not present in the wild type (WT) protein, such as increased or decreased stability, reactivity, or solubility. Experimentalists often have to choose a small subset of mutations from a large number of candidates to obtain the desired change, and computational techniques are invaluable to make the choices. While several such methods have been proposed to predict stability and reactivity mutagenesis, solubility has not received much attention.

Results

We use concepts from computational geometry to define a three body scoring function that predicts the change in protein solubility due to mutations. The scoring function captures both sequence and structure information. By exploring the literature, we have assembled a substantial database of 137 single- and multiple-point solubility mutations. Our database is the largest such collection with structural information known so far. We optimize the scoring function using linear programming (LP) methods to derive its weights based on training. Starting with default values of 1, we find weights in the range [0,2] so that predictions of increase or decrease in solubility are optimized. We compare the LP method to the standard machine learning techniques of support vector machines (SVM) and the Lasso. Using statistics for leave-one-out (LOO), 10-fold, and 3-fold cross validations (CV) for training and prediction, we demonstrate that the LP method performs the best overall. For the LOOCV, the LP method has an overall accuracy of 81%.

Availability

Executables of programs, tables of weights, and datasets of mutants are available from the following web page: http://www.wsu.edu/~kbala/OptSolMut.html.
Signaling network of dendritic cells in response to pathogens: a community-input supported knowledgebase
Authors: Patil Sonali , Pincas Hanna , Seto Jeremy , Nudelman German , Nudelman Irina , Sealfon Stuart C
Published: October 2010

Background

Dendritic cells are antigen-presenting cells that play an essential role in linking the innate and adaptive immune systems. Much research has focused on the signaling pathways triggered upon infection of dendritic cells by various pathogens. The high level of activity in the field makes it desirable to have a pathway-based resource to access the information in the literature. Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks.

Description

We have built a detailed diagram of the dendritic cell signaling network, with the goal of providing researchers with a valuable resource and a facile method for community input. Network construction has relied on comprehensive review of the literature and regular updates. The diagram includes detailed depictions of pathways activated downstream of different pathogen recognition receptors such as Toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors and nucleotide-binding oligomerization domain-like receptors. Initially assembled using CellDesigner software, it provides an annotated graphical representation of interactions stored in Systems Biology Mark-up Language. The network, which comprises 249 nodes and 213 edges, has been web-published through the Biological Pathway Publisher software suite. Nodes are annotated with PubMed references and gene-related information, and linked to a public wiki, providing a discussion forum for updates and corrections. To gain more insight into regulatory patterns of dendritic cell signaling, we analyzed the network using graph-theory methods: bifan, feedforward and multi-input convergence motifs were enriched. This emphasis on activating control mechanisms is consonant with a network that subserves persistent and coordinated responses to pathogen detection.

Conclusions

This map represents a navigable aid for presenting a consensus view of the current knowledge on dendritic cell signaling that can be continuously improved through contributions of research community experts. Because the map is available in a machine readable format, it can be edited and may assist researchers in data analysis. Furthermore, the availability of a comprehensive knowledgebase might help further research in this area such as vaccine development. The dendritic cell signaling knowledgebase is accessible athttp://tsb.mssm.edu/pathwayPublisher/DC_pathway/DC_pathway_index.html.
Differential interleukin-6/Stat3 signaling as a function of cellular context mediates Ras-induced transformation
Authors: Leslie Kenneth , Gao Sizhi P , Berishaj Marjan , Podsypanina Katrina , Ho Hao , Ivashkiv Lionel , Bromberg Jacqueline
Published: October 2010

Introduction

Tyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is expressed in numerous cancers and is required for mediating tumorigenesis. Autocrine and paracrine interleukin (IL)-6 signaling is the principal mechanism by which Stat3 is persistently phosphorylated in epithelial tumors including breast, lung, colon and gastric cancer. The Ras oncogene mediates cellular transformation without evidence of pStat3 in cultured cells. However, non-tyrosine phosphorylated Stat3 was shown to function as a transcriptional activator, localize to the mitochondria and regulate ATP synthesis and mediate cell migration. Here we examined the role of Stat3 in Ras mediated transformation.

Methods

Ha-rasV12 transformed mammary epithelial cells (MCF10A-Ras) cells were transduced with a Stat3shRNA, IL-6shRNA and/or treated with inhibitors of Janus kinases (JAKs) to examine the role of the IL-6 signaling pathway in Ras mediated migration, invasion and tumorigenesis.

Results

Cellular migration, invasion, anchorage independent growth and tumorigenesis were largely abrogated in the Stat3-reduced cells compared to control cells. Analysis of MCF10A-Ras tumors revealed high levels of pStat3 and interleukin-6. Tumors derived from transgenic MMTV-K-Ras mice were also found to express pStat3 and IL-6. MCF10A-Ras cells, when grown in a three-dimensional Matrigel culture system revealed the appearance of the junctional protein E-Cadherin as a consequence of reducing Stat3 levels or inhibiting Stat3 activity. Decreasing IL-6 levels in the MCF10A-Ras cells abrogated tumorigenesis and reduced cell migration. By isolating Ras-expressing primary tumors and serially passaging these cells in two-dimensional culture led to a decrease in IL-6 and pStat3 levels with the reappearance of E-Cadherin.

Conclusions

The cellular and environmental context can lead to differential IL-6/pStat3 signaling and a dependency on this cytokine and transcription factor for migration, invasion and tumorigenesis.
Enhanced density estimation from prestack inversion of multicomponent seismic data
Authors: Leiceaga Gorka Garcia , Silva Josimar , Artola Fredy , Marquez Evelin , Vanzeler Joclean
Published: October 2010

Using 3C-2D seismic data in the Albacora block, Campos Basin, Brazil, we analyzed the potential of multicomponent data for density esti-mation by simultaneously inverting prestack compressional and mode-converted seismic data. Initial forward modeling using the available well logs shows that small changes in density at the reservoir level affect the PS reflectivity more than PP. The inversion engine uses a global optimization algorithm with a nonlinear cost function to simultaneously invert a number of in-put stacks to an Earth model. Inverting solely PP data has shown a lower cor-relation between the estimated density and the measured log in comparison to jointly inverting both PP and PS data. The results also show that adding PS information in the inversion pro-cess improves the density inversion bandwidth and, consequently, inversion resolution.
Time-lapse multicomponent seismic modeling of CO2 fluid substitution in the Devonian Redwater reef, Alberta, Canada
Authors: Sodagar Taher M. , Lawton Don C.
Published: October 2010

The Devonian Redwater reef, northeast of Edmonton, Alberta, is being evaluated for geological storage of [Formula: see text] for the Heartland Area Redwater [Formula: see text] Storage Project (HARP). It is close to large sources of [Formula: see text] in the Redwater-Fort Saskatchewan-Edmonton region. The main objective of the study was to build a 2D geological model of the Redwater reef, from the reef center to off-reef, and investigate the seismic response of the reef to [Formula: see text] saturation in the Leduc Formation. Fluid substitution and seismic modeling were undertaken to generate PP and PS synthetic seismic data to study the consequences of [Formula: see text] saturation on the seismic response of the various reef facies and formations below the reef, based on seismic attributes and character.
Inhibition of the Type 2 Iodothyronine Deiodinase Underlies the Elevated Plasma TSH Associated with Amiodarone Treatment
Authors: Rosene Matthew L. , Wittmann Gábor , Arrojo e Drigo Rafael , Singru Praful S. , Lechan Ronald M. , Bianco Antonio C.
Published: October 2010

The widely prescribed cardiac antiarrhythmic drug amiodarone (AMIO) and its main metabolite, desethylamiodarone (DEA), have multiple side effects on thyroid economy, including an elevation in serum TSH levels. To study the AMIO effect on TSH, mice with targeted disruption of the type 2 deiodinase gene (D2KO) were treated with 80 mg/kg AMIO for 4 wk. Only wild-type (WT) mice controls developed the expected approximate twofold rise in plasma TSH, illustrating a critical role for D2 in this mechanism. A disruption in the D2 pathway caused by AMIO could interfere with the transduction of the T4 signal, generating less T3 and softening the TSH feedback mechanism. When added directly to sonicates of HEK-293 cells transiently expressing D2, both AMIO and DEA behaved as noncompetitive inhibitors of D2 [IC(50) of >100 μm and ∼5 μm, respectively]. Accordingly, D2 activity was significantly decreased in the median eminence and anterior pituitary sonicates of AMIO-treated mice. However, the underlying effect on TSH is likely to be at the pituitary gland given that in AMIO-treated mice the paraventricular TRH mRNA levels (which are negatively regulated by D2-generated T3) were decreased. In contrast, AMIO and DEA both exhibited dose-dependent inhibition of D2 activity and elevation of TSH secretion in intact TαT1 cells, a pituitary thyrotroph cell line used to model the TSH feedback mechanism. In conclusion, AMIO and DEA are noncompetitive inhibitors of D2, with DEA being much more potent, and this inhibition at the level of the pituitary gland contributes to the rise in TSH seen in patients taking AMIO.
Retrograde Endocannabinoid Signaling Reduces GABAergic Synaptic Transmission to Gonadotropin-Releasing Hormone Neurons
Authors: Farkas Imre , Kalló Imre , Deli Levente , Vida Barbara , Hrabovszky Erik , Fekete Csaba , Moenter Suzanne M. , Watanabe Masahiko , Liposits Zsolt
Published: October 2010

Cannabinoids suppress fertility via reducing hypothalamic GnRH output. γ-Aminobutyric acid (GABA)A receptor (GABAA-R)-mediated transmission is a major input to GnRH cells that can be excitatory. We hypothesized that cannabinoids act via inhibiting GABAergic input. We performed loose-patch electrophysiological studies of acute slices from adult male GnRH-green fluorescent protein transgenic mice. Bath application of type 1 cannabinoid receptor (CB1) agonist WIN55,212 decreased GnRH neuron firing rate. This action was detectable in presence of the glutamate receptor antagonist kynurenic acid but disappeared when bicuculline was also present, indicating GABAA-R involvement. In immunocytochemical experiments, CB1-immunoreactive axons formed contacts with GnRH neurons and a subset established symmetric synapses characteristic of GABAergic neurotransmission. Functional studies were continued with whole-cell patch-clamp electrophysiology in presence of tetrodotoxin. WIN55,212 decreased the frequency of GABAA-R-mediated miniature postsynaptic currents (mPSCs) (reflecting spontaneous vesicle fusion), which was prevented with the CB1 antagonist AM251, indicating collectively that activation of presynaptic CB1 inhibits GABA release. AM251 alone increased mPSC frequency, providing evidence that endocannabinoids tonically inhibit GABAA-R drive onto GnRH neurons. Increased mPSC frequency was absent when diacylglycerol lipase was blocked intracellularly with tetrahydrolipstatin, showing that tonic inhibition is caused by 2-arachidonoylglycerol production of GnRH neurons. CdCl2 in extracellular solution can maintain both action potentials and spontaneous vesicle fusion. Under these conditions, when endocannabinoid-mediated blockade of spontaneous vesicle fusion was blocked with AM251, GnRH neuron firing increased, revealing an endogenous endocannabinoid brake on GnRH neuron firing. Retrograde endocannabinoid signaling may represent an important mechanism under physiological and pathological conditions whereby GnRH neurons regulate their excitatory GABAergic inputs.
Metformin Versus Placebo from First Trimester to Delivery in Polycystic Ovary Syndrome: A Randomized, Controlled Multicenter Study
Authors: Vanky Eszter , Stridsklev Solhild , Heimstad Runa , Romundstad Pål , Skogøy Kristin , Kleggetveit Odrun , Hjelle Sissel , von Brandis Philip , Eikeland Torunn , Flo Karin , Berg Kristin Flaten , Bunford Gabor , Lund Agnethe , Bjerke Cecilie , Almås Ingunn , Berg Ann Hilde , Danielson Anna , Lahmami Gulim , Carlsen Sven Magnus
Published: October 2010

Context: Metformin is widely prescribed to pregnant women with polycystic ovary syndrome (PCOS) in an attempt to reduce pregnancy complications. Metformin is not approved for this indication, and evidence for this practice is lacking.

Objectives: Our objective was to test the hypothesis that metformin, from first trimester to delivery, reduces pregnancy complications in women with PCOS.

Design and Setting: We conducted a randomized, placebo-controlled, double-blind, multicenter study at 11 secondary care centers.

Participants: The participants were 257 women with PCOS, in the first trimester of pregnancy, aged 18–42 yr.

Intervention: We randomly assigned 274 singleton pregnancies (in 257 women) to receive metformin or placebo, from first trimester to delivery.

Main Outcome Measures: The prevalence of preeclampsia, gestational diabetes mellitus, preterm delivery, and a composite of these three outcomes is reported.

Results: Preeclampsia prevalence was 7.4% in the metformin group and 3.7% in the placebo group (3.7%; 95% CI, −1.7–9.2) (P = 0.18). Preterm delivery prevalence was 3.7% in the metformin group and 8.2% in the placebo group (−4.4%; 95%, CI, −10.1–1.2) (P = 0.12). Gestational diabetes mellitus prevalence was 17.6% in the metformin group and 16.9% in the placebo group (0.8%; 95% CI, −8.6–10.2) (P = 0.87). The composite primary endpoint prevalence was 25.9 and 24.4%, respectively (1.5%; 95% CI, −8.9–11.3) (P = 0.78). Women in the metformin group gained less weight during pregnancy compared with those in the placebo group. There was no difference in fetal birth weight between the groups.

Conclusions: Metformin treatment from first trimester to delivery did not reduce pregnancy complications in PCOS.
Betting on New Forms of Worker Organization
Authors: Cobble Dorothy Sue
Published: October 2010

I have always admired labor organizers, in part because their long hours and incredible ability to listen, engage, and sympathize with people from every political persuasion make it possible for the labor movement to survive. I do not envy them, however, particularly at this moment in history. They often find themselves in untenable situations, faced with impossible moral and political dilemmas. As one Harvard Union of Clerical and Technical Worker organizer from the Tufts University campaign—where the union recently lost an election—explained to me in January 2010, “You can't win an election without employer neutrality. Yet you can't get neutrality without making concessions you don't want to make.”
Factory Workers in the Hills of West Virginia: The Values and Politics of Rural Industrial Workers in Hancock County, 1930–1965
Authors: Martin Lou
Published: October 2010

When he was a young man in the 1950s and 1960s, Walter Danna used to hunt to supplement his family's diet. He fondly remembered hunting groundhogs, but he cautioned that you had to wait a couple of weeks after they were done hibernating before you bagged them or else they had a “mud taste.” Let them eat some grass and work that out of their system, he said. Danna was not a frontiersman, living in some remote, undeveloped wilderness. He spent his whole career as a steelworker in Hancock County, West Virginia. Yet his experiences and his lifestyle were quite different from industrial workers living in major cities. Steel and pottery workers in the rural environment of Hancock County adapted rural habits to the dictates of modern industrial capitalism. As a result, their values and their politics diverged from those of the more metropolitan segment of the American working class.
No Easy Way Through: Race Leadership and Black Workers at the Nadir
Authors: Kelly Brian
Published: October 2010

It is difficult, even excruciating, to imagine the staggering descent from high optimism to despondency experienced by many African Americans who lived between emancipation and the dawn of the twentieth century. For historians living in the post–civil rights era, recapturing the scale, velocity, and brutality of that dramatic fall has been hampered by two conceptual problems. The first of these, undergirded by prominent trends in the formerly “new” social history, is a widely shared enthusiasm for illuminating those hidden corners of daily life where men and women on the receiving end of Jim Crow continued to wield a degree of control. “Agency” has been the buzzword for a generation of scholarship that emphasizes the staying power and persistence of black Southerners in the face of relentless assaults on their social and economic status, their civil rights, and even, at times, their collective existence. This is, in many ways, an understandable reaction to an earlier consensus that relegated black historical initiative to the margins of a national fable cleansed of unseemly violence and sharp social conflict, but it is also be problematic.
Commutability of National Institute of Standards and Technology standard reference material 1955 homocysteine and folate in frozen human serum for total folate with automated assays
Authors: Ihara Hiroshi , Watanabe Toshiaki , Hashizume Naotaka , Totani Masayuki , Kamioka Kazuyuki , Onda Kimiko , Sunahara Satoshi , Suzuki Tomoko , Itabashi Mitsuharu , Aoki Yoshikazu , Ishibashi Midori , Ito Shozo , Ohashi Koji , Enomoto Tsuyoshi , Saito Kensuke , Saeki Kayoko , Nagamura Yoichi , Nobori Tsutomu , Hirota Kouichi , Fujishiro Kinya , Maekawa Masato , Miura Masakazu , Ohta Yoshiji
Published: October 2010

Background

The aim of the present study was to evaluate standard reference material (SRM) 1955 commutability as a reference material for serum folate using automated methods. We also designed so as to reduce the intermethod variability present in different automated methods.

Methods

Using a microbiological assay related to the ‘information value’ of SRM 1955 as a comparison method, we investigated the possibility of standardization for the assay values of serum folate as measured by the automated methods (Access, Centaur and Elecsys). In the assay of 50 patient sera by these automated methods, we corrected observed values by the SRM 1955 and compared with comparison values.

Results

The observed values of SRM 1955 Levels I, II and III were within or outside (but near) a 95% prediction interval obtained from patient sera by the automated methods. The normalized residuals obtained from SRM 1955 were within ±3.0 (in SD units), which enabled us to conclude that the SRM 1955 had a physicochemical characterization similar to native serum. Twelve patients were assessed as hypofolataemia (<6.0 ng/mL) and 38 patients as normal (≥6.0 ng/mL). Before correction, folate levels in six of 12 patients were lower than 6.0 ng/mL, and those in seven of 38 patients were higher than 6.0 ng/mL with the automated methods. After correction, low levels were found in four of 12 patients, and normal levels were found in 33 of 38 patients.

Conclusions

The use of SRM 1955 would help to reduce the intermethod variability present in different automated methods for serum folate measurement.
Active Learning Projects in Service Operations Management
Authors: Behara Ravi S. , Davis Mark M.
Published: October 2010

Today's students have grown up in the Internet era, where they actively participate in the generation and consumption of information. To create and promote student interest in the classroom, business school faculty therefore have to actively engage them as part of the learning process. This article presents ways in which to incorporate active learning as part of a service operations management (SOM) course at both the undergraduate and graduate levels. We identify specific action learning projects for both levels, based on student maturity and business experience. These projects align with specific topics that are typically presented in a service operations management course. We also present a framework that provides insights for aligning the types of action learning projects with the nature of the data used and the types of intended outcomes. Student feedback suggests that there is significant value in these projects for both the students and faculty.
Cholestatic Pruritus: Sertraline (Adults)
Authors: Generali Joyce A. , Cada Dennis J.
Published: October 2010

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .
Denosumab
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E.
Published: October 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The October 2010 monograph topics are on dapagliflozin, glyco-pyrrolate oral solution, alcaftadine 0.25% ophthalmic solution, fidaxomicin, and cladribine tablets. The DUE/MUE is on memantine.
Mobilizing Care through Portable Information Devices for Patients and Providers
Authors: Felkey Bill G. , Fox Brent I.
Published: October 2010

We are witnessing a convergence of forces that are driving a shift in the US health care system. We have finally recognized the importance to our patients' health of what occurs outside of our health care institutions. Communication with and inclusion of the patient is a new frontier in mobilizing health care delivery. Tools for mobile providers also are receiving heightened attention. These and related topics are addressed in this installment.
Low-Molecular-Weight Heparin Overdose: Management by Observation
Authors: Monte Andrew A , Bodmer Michael , Schaeffer Tammi H
Published: October 2010

Objective:

To describe 3 episodes of low-molecular-weight heparin (LMWH) overdose in 2 patients and discuss the clinical presentations, outcomes, and therapeutic options.

Case Summaries:

The first patient, a 35-year-old female, presented after an intentional overdose of 72,000 units of dalteparin. The peak measured anti-Xa activity was 6.2 U/mL at 7.5 hours postinjection. No interventions were performed and there were no bleeding complications. The patient presented 20 days later following another overdose of 72,000 units. Anti-Xa activity was 4.5 U/mL 2 hours postinjection. No treatment was given and the patient was discharged with plans for follow-up the next day. There was no evidence of bleeding complications on follow-up. The second patient, a 29-year-old male, presented after an intentional overdose of 480 mg of enoxaparin. The anti-Xa activity was 1.9 U/mL measured 2 hours postinjection. The patient was observed without intervention. There were no bleeding complications.

Discussion:

To our knowledge, there is only one previous report of an LMWH overdose in the literature, an iatrogenic overdose in an infant treated with protamine. In our 3 presented episodes of LMWH overdose, no therapeutic interventions were performed and there were no bleeding complications. Review of the literature regarding the efficacy of protamine and recombinant factor VIIa for reversal of LMWH coagulopathy revealed that protamine is only partially effective and recombinant factor VIIa is effective in in vitro studies and case reports.

Conclusions:

In cases of LMWH overdose, observation seems to be appropriate in the absence of clinically significant bleeding. Prolonged monitoring may be necessary for patients with renal failure. Use of protamine or recombinant factor VIIa is not supported by this case series in patients without significant bleeding. There is a lack of data regarding how to treat patients with significant bleeding.
Residency Requirement for Pharmacists Providing Direct Patient Care
Authors: Nahata Milap C
Published: October 2010

A residency requirement has been proposed as a prerequisite for all pharmacists providing direct patient care. This editorial explores the basis for requiring a residency, direct patient care offered by pharmacists with or without a residency, needs to increase interprofessional team–based health care, importance of distinguishing levels of pharmacy practice, role of pharmacy technicians, availability of residency positions, and future of pharmacy residencies. All PharmD graduates should be able to provide a certain level of direct patient care, including medication therapy management services, without completing a residency, and residency programs should be offered for complex levels of direct patient care in all practice settings.