bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient elastography for predicting esophageal/gastric varices in children with biliary atresia
Authors: Chongsrisawat Voranush , Vejapipat Paisarn , Siripon Nipaporn , Poovorawan Yong
Published: May 2011

Background

Transient elastography (TE) is an innovative, noninvasive technique to assess liver fibrosis by measuring liver stiffness in patients with chronic liver diseases. The purpose of this study has been to explore the accuracy of TE and clinical parameters in predicting the presence of esophageal/gastric varices in children with biliary atresia (BA) following portoenterostomy.

Methods

Patients with BA status post portoenterostomy and normal children were recruited. Splenomegaly and presence of EV/GV were determined by physical examination and endoscopy, respectively. Aspartate transaminase to platelet ratio index (APRI) was used as a serum fibrosis marker. TE was performed by using FibroScan. Data was expressed as mean ± SD.

Results

Seventy-three BA patients (male:female = 32:41; age 9.11 ± 5.64 years) and 50 normal controls (male:female = 19:31; age 11.00 ± 3.31 years) were enrolled. The liver stiffness score of BA patients was significantly higher than that of normal controls (27.37 ± 22.48 and 4.69 ± 1.03 kPa; p < 0.001). Patients with EV/GV had significantly higher liver stiffness score and APRI than those without EV/GV. As for EV/GV diagnosis, the areas under the receiver operating characteristic curve were 0.89 (95% CI 0.80 to 0.98) for TE and 0.87 (95% CI 0.78 to 0.96) for APRI, respectively. The sensitivity (and specificity) of TE (using a cut-off value of 12.7 kPa) and APRI (using a cut-off value of 1.92) in predicting EV/GV were 84% (77%) and 84% (83%), respectively, whereas the sensitivity (and specificity) of splenomegaly in predicting EV/GV were 92% (85%).

Conclusions

Transient elastography is a useful tool for predicting the presence of EV/GV. In addition, basic physical examination, routine biochemical and hematological tests, are still worthwhile and correlate well with the presence of EV/GV in patients with BA post portoenterostomy.
Clinical and epidemiological aspects of a hepatitis E outbreak in Bangui, Central African Republic
Authors: Goumba Alice I , Konamna Xavier , Komas Narcisse P
Published: May 2011

Background

Outbreaks of hepatitis E frequently occur in tropical developing countries during the rainy season due to overflowing drains, short-circuiting of networks of clean water and use of contaminated water from wells. Hepatitis E virus (HEV) infections are usually accompanied by general symptoms of acute liver disease. This study was conducted to define the clinical and epidemiological aspects of the HEV outbreak that occurred in May 2004 in Bangui.

Methods

Blood samples were collected from 411 patients aged 1-87 years, most of whom presented with jaundice, asthenia or signs of uncomplicated malaria, for a transversal study from June 2004 to September 2005. Patients were recruited at 11 health care centres, including two referral hospitals, after they had given informed consent. The diagnosis of HEV was made with a commercial ELISA test to detect IgM and/or IgG antibodies. HEV RNA was amplified by RT-PCR to confirm the presence of the viral genome.

Results

The most frequent clinical signs found were jaundice (93.4%), vomiting (50.7%), hepatalgia (47.4%), hepatomegaly (30.9%) and asthenia (26.8%), which are the general clinical signs of hepatic disease. Acute hepatitis E was found in 213 patients (51.8%) who were positive for HEV IgM antibodies. The IgG anti-HEV seroprevalence during this outbreak was high (79.5%). The age group 18-34 years was more frequently infected (91.2%) than those aged 1-17 (78.0%) or over 34 (64.9%) (p < 10-6). RT-PCR performed on 127 sera from the 213 IgM-HEV-positive patients was amplified, and the presence of the viral genome was found in 65 samples.

Conclusion

Although no specific clinical signs exist for hepatitis E infection, people presenting with jaundice, vomiting, hepatalgia, asthenia, hepatomegaly or distended abdomen with no signs of uncomplicated malaria in tropical developing countries should be sent to a laboratory for testing for hepatitis E.
Efficient production of human acidic fibroblast growth factor in pea (Pisum sativum L.) plants by agroinfection of germinated seeds
Authors: Fan Yajun , Li Wei , Wang Junjie , Liu Jingying , Yang Meiying , Xu Duo , Zhu Xiaojuan , Wang Xingzhi
Published: May 2011

Background

For efficient and large scale production of recombinant proteins in plants transient expression by agroinfection has a number of advantages over stable transformation. Simple manipulation, rapid analysis and high expression efficiency are possible. In pea, Pisum sativum, a Virus Induced Gene Silencing System using the pea early browning virus has been converted into an efficient agroinfection system by converting the two RNA genomes of the virus into binary expression vectors for Agrobacterium transformation.

Results

By vacuum infiltration (0.08 Mpa, 1 min) of germinating pea seeds with 2-3 cm roots withAgrobacteriacarrying the binary vectors, expression of the gene for Green Fluorescent Protein as marker and the gene for the human acidic fibroblast growth factor (aFGF) was obtained in 80% of the infiltrated developing seedlings. Maximal production of the recombinant proteins was achieved 12-15 days after infiltration.

Conclusions

Compared to the leaf injection method vacuum infiltration of germinated seeds is highly efficient allowing large scale production of plants transiently expressing recombinant proteins. The production cycle of plants for harvesting the recombinant protein was shortened from 30 days for leaf injection to 15 days by applying vacuum infiltration. The synthesized aFGF was purified by heparin-affinity chromatography and its mitogenic activity on NIH 3T3 cells confirmed to be similar to a commercial product.
Regulation of PBX3 expression by androgen and Let-7d in prostate cancer
Authors: Ramberg Håkon , Alshbib Ayham , Berge Viktor , Svindland Aud , Taskén Kristin Austlid
Published: May 2011

Background

The pre-leukemia transcription factor 3 (PBX) is part of the PBX family of transcription factors, which is known to regulate genes involved in differentiation of urogenital organs and steroidogenesis. This is of interest with regard to prostate cancer progression as regulation of steroidogenesis is one of the mechanisms involved in the development of castration-resistant prostate cancer. In light of this we wanted to investigate the possible involvement of androgen regulation of PBX3 expression in prostate cancer.

Results

In this study, we show that PBX3 is post-transcriptionally regulated by androgen in prostate cancer cells and that the effect might be independent of the androgen receptor. Furthermore, PBX3 was identified as a target of Let-7d, an androgen regulated microRNA. Let-7d was down-regulated in malignant compared to benign prostate tissue, whereas up-regulation of PBX3 expression was observed.

Conclusions

We demonstrate that PBX3 is up-regulated in prostate cancer and post- transcriptionally regulated by androgen through Let-7d.
Interferon signaling patterns in peripheral blood lymphocytes may predict clinical outcome after high-dose interferon therapy in melanoma patients
Authors: Simons Diana L , Lee Gerald , Kirkwood John M , Lee Peter P
Published: May 2011

Background

High-dose Interferon (HDI) therapy produces a clinical response and achieves relapse-free survival in 20-33% of patients with operable high risk or metastatic melanoma. However, patients may develop significant side effects frequently necessitating dose reduction or discontinuation of therapy. We recently showed that peripheral blood lymphocytes (PBL) from some melanoma patients have impaired interferon (IFN) signaling which could be restored with high concentrations of IFN. This exploratory study evaluated IFN signaling in PBL of melanoma patients to assess whether the restoration of PBL IFN signaling may predict a beneficial effect for HDI in melanoma patients.

Methods

PBL from 14 melanoma patients harvested on Day 0 and Day 29 of neoadjuvant HDI induction therapy were analyzed using phosflow to assess their interferon signaling patterns through IFN-α induced phosphorylation of STAT1-Y701.

Results

Patients who had a clinical response to HDI showed a lower PBL interferon signaling capacity than non-responders at baseline (Day 0). Additionally, clinical responders and patients with good long-term outcome showed a significant increase in their PBL interferon signaling from Day 0 to Day 29 compared to clinical non-responders and patients that developed metastatic disease. The differences in STAT1 activation from pre- to post- HDI treatment could distinguish between patients who were inclined to have a favorable or unfavorable outcome.

Conclusion

While the sample size is small, these results suggest that interferon signaling patterns in PBL correlate with clinical responses and may predict clinical outcome after HDI in patients with melanoma. A larger confirmatory study is warranted, which may yield a novel approach to select patients for HDI therapy.
Synthesis of magnetic nanofibers using femtosecond laser material processing in air
Authors: Alubaidy Mohammed-Amin , Venkatakrishnan Krishnan , Tan Bo
Published: May 2011

In this study, we report formation of weblike fibrous nanostructure and nanoparticles of magnetic neodymium-iron-boron (NdFeB) via femtosecond laser radiation at MHz pulse repetition frequency in air at atmospheric pressure. Scanning electron microscopy (SEM) analysis revealed that the nanostructure is formed due to aggregation of polycrystalline nanoparticles of the respective constituent materials. The nanofibers diameter varies between 30 and 70 nm and they are mixed with nanoparticles. The effect of pulse to pulse separation rate on the size of the magnetic fibrous structure and the magnetic strength was reported. X-ray diffraction (XRD) analysis revealed metallic and oxide phases in the nanostructure. The growth of magnetic nanostructure is highly recommended for the applications of magnetic devices like biosensors and the results suggest that the pulsed-laser method is a promising technique for growing nanocrystalline magnetic nanofibers and nanoparticles for biomedical applications.
WFDC1 expression identifies memory CD4 T- lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions
Authors: Alvarez Raymond A , Thorborn Georgina , Reading James L , Reddy Shalini Kamu , Vyakarnam Annapurna
Published: May 2011

Background

Elucidating mechanisms that promote HIV-1 transfer between CD4+ T-lymphocytes and their subsequent loss is of importance to HIV-1 pathogenesis. We recently reported that whey acidic protein, ps20, promotes cell-free HIV-1 spread through ICAM-1 modulation. Since ICAM-1 is pivotal in cell conjugation and intercellular HIV-1 transfer, this study examines ps20 effects on HIV-1 spread between T lymphocytes.

Results

We demonstrate intrinsic ps20 variability in primary CD4+ T-lymphocyte clonal populations and a significant positive correlation between endogenous ps20 levels and virus transfer involving fusion resulting in a spreading infection that could be reversed by the addition of reverse transcriptase inhibitors. Blocking anti-ps20 antibody or siRNA mediated ps20 knockdown, significantly reduced virus transfer. Conversely, virus transfer was promoted by ectopic ps20 expression or by exogenous addition of recombinant ps20. A higher frequency of virological synapse formation was evident in cocultures of HIV-1 infected donor T-cells with ps20high v ps20low/intermediate targets. Blocking ps20 inhibited T-lymphocyte conjugate formation and ICAM-1 expression, and was as potent as ICAM-1 in inhibiting HIV-1 transfer.

Conclusions

Therefore ps20 is a novel marker of CD4+ T-cells rendered vulnerable to HIV-1 infection by regulating the fundamental biologic process of intercellular conjugate formation and consequently of potential importance in HIV-1 pathogenesis.
Enhancement of bacteriolysis of Shuffled phage PhiX174 gene E
Authors: Yu Shen-ye , Peng Wei , Si Wei , Yin Lu , Liu Si-guo , Liu Hui-fang , Zhao Hai-ling , Wang Chun-lai , Chang Yue-hong , Lin Yue-zhi
Published: May 2011

Bacterial ghosts that are generated using the regulated PhiX174 lysis gene E offer a new avenue for the study of inactivated vaccines. Here, we constructed a library of mutant gene E using a gene-shuffling technique. After screening and recombination with the prokaryotic non-fusion expression vector pBV220, two lysis plasmids were selected. Among which, a novel mutant E gene (named mE), consisting of a 74-bp non-encoding sequence at 5'-end and a 201-bp gene ΔE, significantly increased the lysis effect on prokaryotic Escherichia coli and Salmonella enteritidis. Moreover, lysis efficiency, as measured by the OD600 value, reached 1.0 (109 CFU), avoiding the bottleneck problem observed with other bacterial lysis procedures, which results in a low concentration of bacteria in suspension, and consequent low production of bacterial ghosts. Our results may provide a promising avenue for the development of bacterial ghost vaccines.
Cu, Zn-superoxide dismutase 1 (SOD1) is a novel target of Puromycin-sensitive aminopeptidase (PSA/NPEPPS): PSA/NPEPPS is a possible modifier of amyotrophic lateral sclerosis
Authors: Ren Guijie , Ma Zhongcai , Hui Maria , Kudo Lili C , Hui Koon-Sea , Karsten Stanislav L
Published: May 2011

Accumulation of misfolded neurotoxic Cu, Zn-superoxide dismutase-1 (SOD1) protein found in both familial and sporadic amyotrophic lateral sclerosis (ALS) is recognized as an important contributing factor of neuronal cell death. However, little is known about the mechanisms controlling the accumulation and turnover of SOD1 protein. Puromycin-sensitive aminopeptidase (PSA/NPEPPS) was recently identified as a major peptidase acting on neurotoxic TAU protein and protecting against TAU-induced neurodegeneration. In addition, recent report implicated PSA/NPEPPS in the direct removal of neurotoxic polyglutamine repeats. These combined data suggest that PSA/NPEPPS might represent a novel degradation pathway targeting pathologically aggregating neurotoxic protein substrates including SOD1. Here, we report that PSA/NPEPPS directly regulates SOD1 protein abundance and clearance via proteolysis. In addition, PSA/NPEPPS expression is significantly decreased in motor neurons of both SOD

G93A
transgenic mice and sporadic ALS patients, suggesting its possible contribution to the disease pathogenesis. These results implicate SOD1 as a new target protein of PSA/NPEPPS and point to the possible neuroprotective role of PSA/NPEPPS in ALS.
A protein network-guided screen for cell cycle regulators in Drosophila
Authors: Guest Stephen T , Yu Jingkai , Liu Dongmei , Hines Julie A , Kashat Maria A , Finley Russell L
Published: May 2011

Background

Large-scale RNAi-based screens are playing a critical role in defining sets of genes that regulate specific cellular processes. Numerous screens have been completed and in some cases more than one screen has examined the same cellular process, enabling a direct comparison of the genes identified in separate screens. Surprisingly, the overlap observed between the results of similar screens is low, suggesting that RNAi screens have relatively high levels of false positives, false negatives, or both.

Results

We re-examined genes that were identified in two previous RNAi-based cell cycle screens to identify potential false positives and false negatives. We were able to confirm many of the originally observed phenotypes and to reveal many likely false positives. To identify potential false negatives from the previous screens, we used protein interaction networks to select genes for re-screening. We demonstrate cell cycle phenotypes for a significant number of these genes and show that the protein interaction network is an efficient predictor of new cell cycle regulators. Combining our results with the results of the previous screens identified a group of validated, high-confidence cell cycle/cell survival regulators. Examination of the subset of genes from this group that regulate the G1/S cell cycle transition revealed the presence of multiple members of three structurally related protein complexes: the eukaryotic translation initiation factor 3 (eIF3) complex, the COP9 signalosome, and the proteasome lid. Using a combinatorial RNAi approach, we show that while all three of these complexes are required for Cdk2/Cyclin E activity, the eIF3 complex is specifically required for some other step that limits the G1/S cell cycle transition.

Conclusions

Our results show that false positives and false negatives each play a significant role in the lack of overlap that is observed between similar large-scale RNAi-based screens. Our results also show that protein network data can be used to minimize false negatives and false positives and to more efficiently identify comprehensive sets of regulators for a process. Finally, our data provides a high confidence set of genes that are likely to play key roles in regulating the cell cycle or cell survival.
The best practice for preparation of samples from FTA®cards for diagnosis of blood borne infections using African trypanosomes as a model system
Authors: Ahmed Heba A , MacLeod Ewan T , Hide Geoff , Welburn Susan C , Picozzi Kim
Published: May 2011

Background

Diagnosis of blood borne infectious diseases relies primarily on the detection of the causative agent in the blood sample. Molecular techniques offer sensitive and specific tools for this although considerable difficulties exist when using these approaches in the field environment. In large scale epidemiological studies, FTA®cards are becoming increasingly popular for the rapid collection and archiving of a large number of samples. However, there are some difficulties in the downstream processing of these cards which is essential for the accurate diagnosis of infection. Here we describe recommendations for the best practice approach for sample processing from FTA®cards for the molecular diagnosis of trypanosomiasis using PCR.

Results

A comparison of five techniques was made. Detection from directly applied whole blood was less sensitive (35.6%) than whole blood which was subsequently eluted from the cards using Chelex®100 (56.4%). Better apparent sensitivity was achieved when blood was lysed prior to application on the FTA cards (73.3%) although this was not significant. This did not improve with subsequent elution using Chelex®100 (73.3%) and was not significantly different from direct DNA extraction from blood in the field (68.3%).

Conclusions

Based on these results, the degree of effort required for each of these techniques and the difficulty of DNA extraction under field conditions, we recommend that blood is transferred onto FTA cards whole followed by elution in Chelex®100 as the best approach.
Breaking evolutionary and pleiotropic constraints in mammals: On sloths, manatees and homeotic mutations
Authors: Varela-Lasheras Irma , Bakker Alexander J , van der Mije Steven D , Metz Johan AJ , van Alphen Joris , Galis Frietson
Published: May 2011

Background

Mammals as a rule have seven cervical vertebrae, except for sloths and manatees. Bateson proposed that the change in the number of cervical vertebrae in sloths is due to homeotic transformations. A recent hypothesis proposes that the number of cervical vertebrae in sloths is unchanged and that instead the derived pattern is due to abnormal primaxial/abaxial patterning.

Results

We test the detailed predictions derived from both hypotheses for the skeletal patterns in sloths and manatees for both hypotheses. We find strong support for Bateson's homeosis hypothesis. The observed vertebral and rib patterns cannot be explained by changes in primaxial/abaxial patterning. Vertebral patterns in sloths and manatees are similar to those in mice and humans with abnormal numbers of cervical vertebrae: incomplete and asymmetric homeotic transformations are common and associated with skeletal abnormalities. In sloths the homeotic vertebral shift involves a large part of the vertebral column. As such, similarity is greatest with mice mutant for genes upstream of Hox.

Conclusions

We found no skeletal abnormalities in specimens of sister taxa with a normal number of cervical vertebrae. However, we always found such abnormalities in conspecifics with an abnormal number, as in many of the investigated dugongs. These findings strongly support the hypothesis that the evolutionary constraints on changes of the number of cervical vertebrae in mammals is due to deleterious pleitropic effects. We hypothesize that in sloths and manatees low metabolic and activity rates severely reduce the usual stabilizing selection, allowing the breaking of the pleiotropic constraints. This probably also applies to dugongs, although to a lesser extent.
High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus
Authors: Abdulahad Deena A , Westra Johanna , Bijzet Johannes , Limburg Pieter C , Kallenberg Cees GM , Bijl Marc
Published: May 2011

Introduction

High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein. HMGB1, which is secreted by inflammatory cells and passively released from apoptotic and necrotic cells, may act as a pro-inflammatory mediator. As apoptotic cells accumulate in systemic lupus erythematosus (SLE), HMGB1 levels might be increased in SLE. HMGB1 may also serve as an autoantigen, leading to the production of anti-HMGB1 antibodies. In this study we determined levels of HMGB1 and anti-HMGB1 in SLE patients in comparison to healthy controls (HC) and analysed their relation with disease activity.

Methods

The study population consisted of 70 SLE patients and 35 age- and sex-matched HC. Thirty-three SLE patients had quiescent disease, the other 37 patients were selected for having active disease. Nineteen of these had lupus nephritis. HMGB1 levels were measured with both Western blot and ELISA. Anti-HMGB1 levels were measured by ELISA. Clinical and serological parameters were assessed according to routine procedures.

Results

HMGB1 levels in SLE patients could be measured reliably by Western blotting only, and were significantly increased compared to HC. During active disease HMGB1 levels increased, in particular in patients with renal involvement. Serum HMGB1 levels correlated with SLEDAI, proteinuria, and anti-dsDNA levels, and showed a negative correlation with complement C3. Anti-HMGB1 levels were significantly increased in SLE patients compared to HC, and positively correlated with HMGB1 levels.

Conclusions

Levels of HMGB1 in the sera of SLE patients, in particular in those with active renal disease, are increased. Serum HMGB1 levels are related to SLEDAI scores and proteinuria, as well as to levels of anti-HMGB1 antibodies. These findings suggest that besides HMGB1, HMGB1-anti-HMGB1 immune complexes play a role in the pathogenesis of SLE, in particular in patients with renal involvement.
High-resolution passive seismic tomography for 3D velocity, Poisson’s ratioν, and P-wave qualityQPin the Delvina hydrocarbon field, southern Albania
Authors: Tselentis G-Akis , Martakis Nikolaos , Paraskevopoulos Paraskevas , Lois Athanasios
Published: May 2011

We have studied using traveltimes of P- and S-waves and initial seismic-pulse rise-time measurements from natural microearthquakes to derive 3D P-wave velocity VPinformation (mostly structural) as well as P- and S-wave velocity VP/VSand P-wave quality factor QPinformation (mostly lithologic) in a known hydrocarbon field in southern Albania. During a 12-month monitoring period, 1860 microearthquakes were located at a 50-station seismic network and were used to obtain the above parameters. The data set included earthquakes with magnitudes ranging from –0.1 to 3.0 R (Richter scale) and focal depths typically occurring between 2 and 10 km. Kohonen neural networks were implemented to facilitate the lithological classification of the passive seismic tomography (PST) results. The obtained results, which agreed with data from nearby wells, helped delineate the structure of the reservoir. Two subregions of the investigated area, one corresponding to an oil field and one to a gas field, were correlated with the PST results. This experiment showed that PST is a powerful new geophysical technique for exploring regions that present seismic penetration problems, difficult topographies, and complicated geologies, such as thrust-belt regions. The method is economical and environmentally friendly, and it can be used to investigate very large regions for the optimal design of planned 2D or 3D conventional geophysical surveys.
Dynamic of oxidative and nitrosative stress markers during the convalescent period of stroke patients undergoing rehabilitation
Authors: Manolescu Bogdan Nicolae , Berteanu M , Oprea E , Chiriac N , Dumitru L , Vlădoiu S , Popa O , Ianăş O
Published: May 2011

Background

Stroke patients have a redox imbalance, a consequence of both the cerebrovascular event and the associated pathological conditions. Our study was aimed to investigate the dynamic of some oxidative and nitrosative markers during the convalescent phase of postacute stroke patients undergoing rehabilitation.

Methods

We assessed thiol, advanced oxidation protein product, protein carbonyl, 3-nitro-l-tyrosine, ceruloplasmin and oxidized LDL concentrations, as well as gamma-glutamyltranspeptidase (GGT) activity in 20 patients at the beginning of the hospitalization and at the discharge moment, respectively, and 24 apparently healthy controls.

Results

We found significantly increased values for GGT ( P = 0.04), ceruloplasmin ( P = 0.01) and protein carbonyl ( P = 0.04) in stroke patients at the hospitalization moment when compared with healthy controls, while total thiols were significantly decreased ( P = 0.002). Rehabilitation was associated with a significant decrease of protein carbonyl ( P = 0.03) and oxidized LDL particle concentrations ( P = 0.03), as well as GGT activity ( P = 0.02). At the hospitalization moment, both GGT and ceruloplasmin were significantly negatively correlated with non-proteic thiols ( r = −0.44, P = 0.049, and r = −0.53, P = 0.015, respectively) and significantly positively with protein carbonyls ( r = +0.80, P < 0.001, and r = +0.69, P < 0.001, respectively) suggesting putative roles of GGT and ceruloplasmin in the redox imbalance.

Conclusions

These results highlight the existence of a redox imbalance in postacute stroke patients, and the possible benefits of an antioxidant-based therapy for the recovery of these patients.
Corrections to Papers by Montgomery and Klatt
Authors: Alt Francis B.
Published: May 2011

In a series of papers dealing with the economic design of T2 control charts, Montgomery and Klatt incorrectly use the T2 statistic. This note locates their error and gives the correct method of solution.
Gemcitabine and Carboplatin (GC) Regimen for Advanced Non-Small-Cell Lung Cancer
Authors: King Crystal L. , Waddell J. Aubrey , Solimando Dominic A.
Published: May 2011

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Being Successful as a Mentor
Authors: White Sara J.
Published: May 2011

This article is intended to be practical advice on mentoring for pharmacists and pharmacy faculty. It defines successful mentoring and provides approaches for mentors to find out who the mentee is as a person, where they are currently, where they would like to go, and how to customize mentoring techniques.
New Drugs Approved by the FDA; New Dosage Forms and Indications Approved by the FDA; Agents Pending FDA Approval; New Drug/Biologics License Applications Filed by Manufacturer; Significant Labeling Changes or “Dear Health Professional” Letters Related to Safety
Authors: Baker Danial E.
Published: May 2011

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at bakerdan@wsu.edu .
340B Drug Pricing Program: Interpreting Regulations and Exploring Opportunities
Authors: Eggers Garrett G. , Mark Scott M. , Weber Robert J.
Published: May 2011

The Director's Forum series is edited by Robert J. Weber and Scott M. Mark and is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. This article focuses on an important program for expanding pharmacy practice models to uninsured and underinsured patients. The 340B program provides assistance to hospitals on drug pricing to allow organizations sufficient additional savings to channel to patients in need. The regulations surrounding eligibility, drug pricing, and pharmacy contracting are complex and can make participating in 340B seem intimidating and unattractive to potentially eligible organizations. By gaining further understanding of the intricacies of the 340B Drug Pricing Program, pharmacists and other health care providers can utilize the program to maximize the benefit for both their patients and their organization.
Size Effect Related to Composite Toughness Characterization
Authors: Yotte Sylvie , Breysse Denys
Published: May 2011

This paper deals with toughness characterization of composite materials. In that case, Linearly Elastic Fracture Mechanics (LEFM) may not be effective because a damage zone develops at the notch tip during crack propagation. Experimental tests were carried out on two different series of homothetic specimens (Single Edge Notched Tensile and Steel Frame Assisted Tension). Data gathered for the tested sample sizes confirmed that LEFM cannot be used for toughness characterization. A macroscopic failure criterion was hence derived from experimental data. Acoustic emission data indicated fiber bridging as the main mechanism opposing crack propagation. The corresponding microscopic failure criterion is chosen to define a test-independent criterion. Cumulative statistical distributions of test-independent failure parameters were finally determined on the basis of all experimental results.
Derivation of Clinically Relevant Boundary Conditions Suitable for Evaluation of Chronic Impingement of Lumbar Total Disk Replacement: Application to Standard Development
Authors: Rundell S. A. , Day J. S. , Isaza J. , Siskey R. , MacDonald D. , Kurtz S. M.
Published: May 2011

Currently available standardized methods for evaluating the long-term wear of total disk replacements do not incorporate the effects of potential device impingement. Creation of a standard that incorporates device impingement is difficult without a thorough understanding of the associated biomechanical environment. Arbitrary modification of the currently available wear-test protocols to account for device impingement may add unnecessary cost, and potentially inaccurate, unrealistic results. Finite element models provide the ability to control variation and test for a wide range of parameters without the excessive time and monetary costs associated with cadaveric testing or wear simulations. However, careful validation and verification of these models is required in order to ensure predictability. Retrieved implants can be used to validate the clinical predictability of finite element models (FEMs). The objective of the current study was to quantify the ability of a previously developed FEM of the lumbar spine to predict polyethylene damage modes and impingement in actual clinical scenarios, and extract the loading and boundary conditions for implementation into a new lumbar TDR wear simulation standard. In order to achieve this objective, actual clinical scenarios, associated with retrieved implants, were modeled and simulated. We hypothesized that clinical damage modes, including both impingement and non-impingement scenarios, can be predicted using a FEM that incorporates case-specific clinical factors, anterior-posterior shear forces, coupled translations, and facet contact.
A Clustering Analysis Model for Golden Die Extractions Based on Wafer Acceptance Test at Semiconductor R&D Stage
Authors: Liu S. F. , Chen F. L. , Lin S. C. , Chang K. J. , Yu S. M.
Published: May 2011

During the research and development (R&D) stage of semiconductor fabrication, the R&D engineers make a lot of effort to identify golden dice that meet simulated performance of circuit design. With feedback from wafer acceptance test (WAT) data of the golden dice, the efficiency of process window analysis can be further improved. However, it is difficult for current practices to select golden dice due to limited time and cost concerns. In this research, an analytical model is proposed to analyze WAT data during the R&D stage of semiconductor fabrication to assist R&D engineers in resolving these critical issues. WAT data are collected and utilized to classify dice on a wafer and similar golden dice are then identified based on pre-defined golden dice. Similar golden dice can provide much more important feedback from WAT data, and the efficiency of process window analysis can then be improved. Real WAT data at the R&D stage during semiconductor fabrication were collected from a famous semiconductor manufacturing company and were experimented through the presented methodology. Experimental results show that the presented model can successfully extract representative similar golden dice within clusters. With advice from R&D engineers, the representative similar golden dice extracted from this work are sufficient for subsequent process window analysis.
“—wie ihn uns Meister Dürer gemalt!”: Contest, Myth, and Prophecy in Wagner's Die Meistersinger von Nürnberg
Authors: Goehr Lydia
Published: May 2011

Wagner introduced into the very first scene of his opera Die Meistersinger von Nürnberg a brief description of an image of David slaying Goliath. He attributed the image to Albrecht Dürer. But did Dürer actually produce this image? To answer the question, this essay assumes the form of a “had I but known” mystery story to explore the mythological and theological foundations of Wagner's opera of contest, myth, and prophecy. The quest for Dürer's image is set against three contests: between Apollo and Marsyas; between the arts of music, poetry, and painting; and between composers, painters, and poets. The essay draws upon these contests to make explicit the unfolding of a drama that begins with an image in which the old King David of the harp is displaced by a young King David of the sword. The question is: who exactly is the young David?
Testicular size development and reproductive hormones in boys and adult males with Noonan syndrome: a longitudinal study
Authors: Ankarberg-Lindgren Carina , Westphal Otto , Dahlgren Jovanna
Published: May 2011

Objective

To characterise changes in testicular size and reproductive hormones and to investigate the aetiology of delayed puberty and impaired fertility in males with Noonan syndrome (NS).

Design

In this study, 12 males with NS were longitudinally followed from pre/early puberty until adulthood. Of the 12 males, ten had no medical history other than NS and were divided into two groups, undescended testes (UT), and descended testes (DT) and compared with a reference population.

Methods

Hormone concentrations in serum were determined by immunoassays and testicular volume was measured using an orchidometer.

Results

Before puberty, reproductive hormone levels were within the expected range in almost all cases. In some cases, LH, FSH and testosterone and oestradiol (E2) concentrations started to increase during puberty and inhibin B and anti-Müllerian hormone (AMH) declined to subnormal levels. Most of the boys studied had small testes that, in the majority of cases, progressed to normal size in adulthood. No difference in reproductive hormones was observed between the UT and DT groups either during puberty or at adulthood. However, as adults, males with NS had higher LH (5.7 vs 4.0 U/l, P<0.01), FSH (7.1 vs 2.5 U/l, P<0.001), testosterone (18.7 vs 15.6 nmol/l, P<0.01) and E2 (66 vs 46 pmol/l, P<0.001) levels and lower AMH (33 vs 65 pmol/l, P<0.01) and inhibin B (median 108 vs 187 pg/ml, P<0.01) levels than the reference population.

Conclusions

In NS males, both Sertoli and Leydig cell dysfunction is common with reproductive hormone levels deteriorating progressively to adulthood.
The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells
Authors: Gravina Giovanni Luca , Marampon Francesco , Petini Foteini , Biordi Leda , Sherris David , Jannini Emmanuele A , Tombolini Vincenzo , Festuccia Claudio
Published: May 2011

One of the major obstacles in the treatment of hormone-refractory prostate cancer (HRPC) is the development of chemo-resistant tumors. The aim of this study is to evaluate the role of Palomid 529 (P529), a novel TORC1/TORC2 inhibitor, in association with docetaxel (DTX) and cisplatin (CP). This work utilizes a wide panel of prostatic cancer cell lines with or without basal activation of Akt as well as twoin vivomodels of aggressive HRPC. The blockade of Akt/mTOR activity was associated to reduced cell proliferation and induction of apoptosis. Comparison of IC50 values calculated for PTEN-positive and PTEN-negative cell lines as well as the PTEN transfection in PC3 cells or PTEN silencing in DU145 cells revealed that absence of PTEN was indicative for a better activity of the drug. In addition, P529 synergized with DTX and CP. The strongest synergism was achieved when prostate cancer (PCa) cells were sequentially exposed to CP or DTX followed by treatment with P529. Treatment with P529 before the exposure to chemotherapeutic drugs resulted in a moderate synergism, whereas intermediated values of combination index were found when drugs were administered simultaneously.In vivotreatment of a combination of P529 with DTX or CP increased the percentage of complete responses and reduced the number of mice with tumor progression. Our results provide a rationale for combinatorial treatment using conventional chemotherapy and a Akt/mTOR inhibitor as promising therapeutic approach for the treatment of HRPC, a disease largely resistant to conventional therapies.
Becoming more focused therapeutic lipid patterns: results from the Hungarian MULTI GAP 2010
Authors: Reiber István , Paragh György , Márk László , Pados Gyula
Published: May 2011

Previous studies have found that many high-risk patients are not achieving their LDL-cholesterol goals, and many patients, despite being treated with lipid-lowering therapy, also have elevated triglycerides and/or low levels of HDL-cholesterol. Aims: Authors analyzed the treatment strategies for dyslipidemic subjects following cardiovascular events similarly to their former survey from 2008 and 2009. Methods: In the MULTI GAP (MULTI Goal Attainment Problem) 2010 trial data from standard and structured questionnaires of 2332 patients were processed. Authors analyzed the proportion of the patients reaching target levels for total cholesterol, LDL-C, HDL-C, A-C (atherogen cholesterol) and triglyceride. Results: 15% (n = 355) of the patients did not receive any lipid lowering treatment. 44% of the patients treated by specialists reached the target LDL-C level of 2.5 mmol/l. In „high risk” group target levels for HDL-C were reached by 61% of the patients, and for triglyceride by 43% of the subjects. 43% of the patients with the best compliance (>90%) reached the target LDL-C level of 2.5 mmol/l. Conclusion: There is a need for more effective lipid lowering therapy with more frequent use of higher doses of statins or combinations of lipid lowering drugs. Orv. Hetil., 2011, 152, 822–827.
A linguistic approach in culturally and linguistically diverse classrooms
Authors: de Oliveira Luciana C.
Published: May 2011

This article describes the application of systemic functional linguistics (Halliday & Matthiesen, 2004; Martin & Rose, 2005) to the teaching of science in a 4th grade classroom in the United States. Drawing on different data sources, including classroom lessons and planning meetings between a teacher educator and a teacher, a framework for working with mainstream content-area teachers is mapped out, based on work on the teaching/learning cycle (Rothery, 1994) and the notion of scaffolding (Hammond, 2001) applied to teacher education.
Understanding joint construction in the tertiary context
Authors: Dreyfus Shoshana J. , Macnaught Lucy , Humphrey Sally
Published: May 2011

The importance of teacher-student collaboration in text production is well established in education literature (Cazden 1996; Green 1988; Mehan 1979). Teacher-student collaboration is a key feature of Sydney School Genre pedagogy, particularly in the Joint Construction stage of the Teaching Learning cycle. Joint Construction supports the literacy development of all students through dialogic exchanges that enable the co-creation of a target text (Rothery & Stenglin 1995). While this stage of the Teaching Learning cycle has been widely used across primary, secondary and tertiary contexts, teacher-student dialogue in text production has only been analysed in detail at a primary school level (see Hunt 1991 & 1994). This paper examines three Joint Construction lessons from the tertiary context. Using phasal analysis (Gregory 1985, 1988), it examines how different stages of Joint Construction achieve their goals. Using exchange structure analysis (Sinclair & Coulthard 1975; Berry 1981; Ventola 1987 & 1988; Martin 2007; Author 2007), which is located within the discourse semantic system of NEGOTIATION (Martin & Rose 2007), the paper provides a principled linguistic analysis of the conversational moves taking place.
‘It’s really a great presentation!’
Authors: Lipovsky Caroline
Published: May 2011

It is crucial that interviewers in job interviews make a good impression on candidates so they can attract the right person for the position they need to fill. The large body of literature on job interviews however mostly focuses on interviewers’ impressions of the candidates. This study aims at redressing the imbalance by examining interviewers’ impression management strategies. In particular, it explores the ways in which interviewers evaluate candidates in the course of their interviews. Drawing on systemic functional linguistics, and in particular on Appraisal theory (Martin and White, 2005), this paper examines a set of authentic job interviews in French, or French and English. The analysis of the job interviews is complemented by analysis of participants’ comments on their interviews. The first analysis reveals an evaluative stance that is overwhelmingly positive and favourable to candidates, while the second shows candidates’ positive reaction and alignment to their interviewers’ appraisal.
Genetics of Nonsyndromic Orofacial Clefts
Authors: Rahimov Fedik , Jugessur Astanand , Murray Jeffrey C.
Published: May 2011

With an average worldwide prevalence of approximately 1.2/1000 live births, orofacial clefts are the most common craniofacial birth defects in humans. Like other complex disorders, these birth defects are thought to result from the complex interplay of multiple genes and environmental factors. Significant progress in the identification of underlying genes and pathways has benefited from large populations available for study, increased international collaboration, rapid advances in genotyping technology, and major improvements in analytic approaches. Here we review recent advances in genetic epidemiological approaches to complex traits and their applications to studies of nonsyndromic orofacial clefts. Our main aim is to bring together a discussion of new and previously identified candidate genes to create a more cohesive picture of interacting pathways that shape the human craniofacial region. In future directions, we highlight the need to search for copy number variants that affect gene dosage and rare variants that are possibly associated with a higher disease penetrance. In addition, sequencing of protein-coding regions in candidate genes and screening for genetic variation in noncoding regulatory elements will help advance this important area of research.
Motivations of Orthodontic Residents in Canada and the United States to Treat Patients with Craniofacial Anomalies, Cleft Lip/Palate, and Special Needs
Authors: Noble James , Schroth Robert J. , Hechter Frank J. , Huminicki Amanda , Wiltshire William A.
Published: May 2011

Objectives

To determine the motivation of orthodontic residents in Canada and the United States to treat patients with cleft lip/palate (CLP), craniofacial anomalies (CFA), and special needs (SN).

Methods

In March 2009, an e-mail with a link to a 41-item survey was sent to all orthodontic residents in Canada and the United States (n = 944).

Results

Of 944 residents contacted, 339 viewed and 208 completed the survey (22.03%). Using a seven-point Likert scale, residents recognized the importance of treating patients with CLP/CFA/SN. When asked if they plan to treat patients with CLP/CFA/SN, 54.48% responded yes, 13.46% no, and 36.06% were unsure. A total of 38.05% said they would charge the same fee as a typical multiarch case, while 58.05% would charge more, and 60% of fourth-year residents would charge twice the fee. Of the respondents, 43.00% were aware of the established fellowship programs in CLP/CFA/SN. Canadian residents (67.9%) were more enthusiastic about completing a fellowship than Americans were. Of the respondents, 29.33% would complete a 1-year fellowship, while 70.67% would not. A total of 78.4% of male respondents and 77.4% of American residents indicated they would not pursue a fellowship.

Conclusions

Residents supported the importance of treating patients with CLP/CFA/SN, and more than 54% indicated they plan to treat these patients. Residents who indicated that they would not treat these patients sited limited experience and inadequate expertise as the reasons. Less than 30% indicated a willingness to pursue a fellowship program.