bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic and field-based electrical imaging of a zerovalent iron barrier: Implications for monitoring long-term barrier performance
Authors: Slater Lee , Binley Andrew
Published: September 2006

We performed a study of electrical imaging sensitivity to geochemical alteration of a zerovalent iron permeable reactive barrier (PRB) over time. Complex-resistivity measurements of laboratory cores from an operational PRB defined the electrical properties of both unreacted and geochemically altered (reacted) iron, as well as the growth rate of the reacted front on the up gradient edge of the barrier. Laboratory results were used to generate models of the electrical structure of the PRB at 0, 15, and 30 years of operation. Synthetic cross-borehole resistivity and induced-polarization data were generated and perturbed with errors representative of noise at the site. To generate reliable images of the engineered structure, a complex-resistivity inversion was employed with a disconnect in the regularization between the part of the finite-element mesh (FEM) representing the internal structure of the barrier and the remainder of the FEM mesh.Synthetic results show that although the internal structure of inverted images at 15 and 30 years does not accurately reflect the width of the reacted front, modeled along the up-gradient edge of the barrier, perturbations to the internal structure of the imaged PRB are diagnostic of the growth of the reacted front. Cross-borehole electrical data, obtained at the field site during a 15-month period, demonstrate that the complex-resistivity algorithm can resolve reliably the PRB target using the engineering design specifications to define the correct shape of the regularization disconnect. Both resistivity and induced-polarization reciprocal errors are low, and the induced-polarization data are highly repeatable over this period. Changes in the electrical properties of the PRB over time were small but consistent with growth of a reacted front, based on the synthetic study. Significantly, resistivity imaging alone may be sufficient for long-term monitoring of precipitation, leading to reduced PRB performance.
The influence of crack shape on the effective elasticity of fractured rocks
Authors: Grechka Vladimir , Vasconcelos Ivan , Kachanov Mark
Published: September 2006

A circle is the basic fracture shape adopted by conventional effective media theories to describe the overall elasticity of cracked solids. Fractures in rocks do not resemble circles, so it is important to find out to what extent the available theoretical results apply to realistic fracture shapes. To address this issue, we conduct 3D numerical experiments on the so-called digital rocks containing irregular cracks that might be partially closed and might intersect each other. Despite profound deviations of our fracture geometries from circles, we find that basic theoretical results originally developed for penny-shaped cracks remain valid for arbitrary fracture shapes. Based on a series of finite-element computations, we show that as far as the effective elasticity is concerned, flat fractures with random in-plane irregularities are represented accurately by circular ones. We also show that approximate effective elliptical orthotropy established for multiple sets of dry, penny-shaped cracks embedded in isotropic host rock holds with the same accuracy for irregular, possibly intersecting fractures.
3D modeling of a deepwater EM exploration survey
Authors: Michael Hoversten G. , Newman Gregory A. , Geier Nathan , Flanagan Guy
Published: September 2006

Analysis of a current offshore prospect employed 3D numerical modeling of a controlled-source electromagnetic (CSEM) exploration system. The analysis considers the sensitivity of data presentations to assumptions about the background model. The numerical simulations show that false anomalies and significant distortion to anomaly magnitude can be caused by normalization of the observed electric fields by reference fields calculated from an incorrect or oversimplified background model. Bathymetry effects on the measured electric fields, if not accounted for, can produce anomalies as large as those of target sands. The maximum sensitivity to oil-water contacts or other strong lateral variations within the modeled channel sands is achieved by profiling along the length of the channel. Profiles run offset from a simulated oil-water contact by as little as [Formula: see text] show a response below the expected noise levels. Good background models can be constructed by taking advantage of the magnetotelluric data recorded by marine receivers during times when the CSEM transmitter is not in operation. The effects of electrical anisotropy can produce anomalies as large as target responses, although the spatial pattern of sheetlike anisotropic zones can be distinguished from the spatial pattern of sand-channel anomalies.
Calculation of magnitude magnetic transforms with high centricity and low dependence on the magnetization vector direction
Authors: Gerovska Daniela , Araúzo-Bravo Marcos J.
Published: September 2006

We present a Matlab tool that calculates five magnitude magnetic transforms (MMTs) from an input measured anomalous magnetic field. The MMTs are all based on the total magnitude anomaly (TMA), and consist of the TMA itself, the modulus of the gradient of the TMA, the Laplacian of the TMA, half of the square root of the Laplacian of the square of the TMA, and the square root of the product of the TMA plus the Laplacian of the TMA. These MMTs produce anomalies that are closer to the magnetic source’s true horizontal position and are simpler to interpret than the measured anomalous magnetic field itself. While the conventional magnetic transforms of reduction-to-the-pole (RTP), the pseudogravity field, and the analytic signal (AS) also have these properties, these MMTs have several additional advantages. They require only first-order, horizontal derivatives for their calculation. They are also more stable at low magnetic latitudes than the RTP, and have a pattern that is independent of the geomagnetic-field vector direction, in contrast to the AS.

The Matlab tool is designed to deal with big data sets and is compatible with common data formats, GS ASCII grid files, and XYZ data files. A calculation of the MMTs of the total magnetic anomaly of a synthetic example at a low magnetic latitude and with a field example from the Kuju volcanic area, Japan demonstrate the effectiveness of the program.
Anisotropic geometrical-spreading correction for wide-azimuth P-wave reflections
Authors: Xu Xiaoxia , Tsvankin Ilya
Published: September 2006

Compensation for geometrical spreading along a raypath is one of the key steps in AVO (amplitude-variation-with-offset) analysis, in particular, for wide-azimuth surveys. Here, we propose an efficient methodology to correct long-spread, wide-azimuth reflection data for geometrical spreading in stratified azimuthally anisotropic media. The P-wave geometrical-spreading factor is expressed through the reflection traveltime described by a nonhyperbolic moveout equation that has the same form as in VTI (transversely isotropic with a vertical symmetry axis) media.

The adapted VTI equation is parameterized by the normal-moveout (NMO) ellipse and the azimuthally varying anellipticity parameter [Formula: see text]. To estimate the moveout parameters, we apply a 3D nonhyperbolic semblance algorithm of Vasconcelos and Tsvankin that operates simultaneously with traces at all offsets andazimuths. The estimated moveout parameters are used as the input in our geometrical-spreading computation. Numerical tests for models composed of orthorhombic layers with strong, depth-varying velocity anisotropy confirm the high accuracy of our travetime-fitting procedure and, therefore, of the geometrical-spreading correction. Because our algorithm is based entirely on the kinematics of reflection arrivals, it can be incorporated readily into the processing flow of azimuthal AVO analysis.

In combination with the nonhyperbolic moveout inversion, we apply our method to wide-azimuth P-wave data collected at the Weyburn field in Canada. The geometrical-spreading factor for the reflection from the top of the fractured reservoir is clearly influenced by azimuthal anisotropy in the overburden, which should cause distortions in the azimuthal AVO attributes. This case study confirms that the azimuthal variation of the geometrical-spreading factor often is comparable to or exceeds that of the reflection coefficient.
Prospective Study of [18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography and Magnetic Resonance Imaging in Oral Cavity Squamous Cell Carcinoma With Palpably Negative Neck
Authors: Ng Shu-Hang , Yen Tzu-Chen , Chang Joseph Tung-Chieh , Chan Sheng-Chieh , Ko Sheung-Fat , Wang Hung-Ming , Lee Li-Yu , Kang Chung-Jan , Wong Alex Mun-Ching , Liao Chun-Ta
Published: September 2006

Purpose

To assess the clinical usefulness of [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) as well as computed tomography (CT) or magnetic resonance imaging (MRI) in oral squamous cell carcinoma (SCC) patients with palpably negative neck.

Patients and Methods

In total, 134 oral SCC patients with palpably negative neck were prospectively evaluated with [18F]FDG PET, CT/MRI, and their visual correlation. Histopathologic analysis was used as the gold standard for assessment of these imaging techniques.

Results

Thirty-five (26.1%) of our 134 patients were found to have neck metastases. On a level-by-level basis, the sensitivity of [18F]FDG PET for nodal metastases was two-fold higher than that of CT/MRI (41.2% v 21.6%, respectively; P = .021). Visual correlation of [18F]FDG PET and CT/MRI yielded slightly higher sensitivity and specificity than [18F]FDG PET alone (47.1% v 41.2%, P = .25; 98.0% v 96.8%, P = .125, respectively). On a patient-by-patient basis, the sensitivity of [18F]FDG PET for neck metastases was 51.4% and increased to 57.1% after visual correlation with CT/MRI. The probabilities of occult neck metastasis after using [18F]FDG PET were 6.7% in T1 tumors, 10.8% in T2 tumors, 13.3% in T3 tumors, and 25% in T4 tumors and decreased to 3.3% in T1 tumors and to 9.2% in T2 tumors after visual correlation with CT/MRI.

Conclusion

[18F]FDG PET was superior to CT/MRI for detecting palpably occult neck metastasis of oral SCC. Because [18F]FDG PET could reduce the probability of occult neck metastasis to less than 15% in T1 to T3 tumors, it should be indicated for evaluation of these subpopulations.
Breast Cancer Treatment of Older Women in Integrated Health Care Settings
Authors: Enger Shelley M. , Thwin Soe Soe , Buist Diana S.M. , Field Terry , Frost Floyd , Geiger Ann M. , Lash Timothy L. , Prout Marianne , Yood Marianne Ulcickas , Wei Feifei , Silliman Rebecca A.
Published: September 2006

Purpose

A substantial literature describes age-dependent variations in breast cancer treatment, showing that older women are less likely to receive standard treatment than younger women. We sought to identify patient and tumor characteristics associated with the nonreceipt of standard primary tumor and systemic adjuvant therapies.

Patients and Methods

We studied 1,859 women age 65 years or older with stage I and II breast cancer diagnosed between 1990 and 1994 who were cared for in six geographically dispersed community-based health care systems. We collected demographic, tumor, treatment, and comorbidity data from electronic data sources, including cancer registry, administrative, and clinical databases, and from subjects' medical records.

Results

Women 75 years of age or older and women with higher comorbidity indices were more likely to receive nonstandard primary tumor therapy, to not receive axillary lymph node dissection, and to not receive radiation therapy after breast-conserving surgery (BCS). Asian women were less likely to receive BCS, and African American women were less likely to be prescribed tamoxifen. Although nonreceipt of most therapies was associated with a lower baseline risk of recurrence, an important minority of high-risk women (16% to 30%) did not receive guideline therapies.

Conclusion

Age is an independent risk factor for nonreceipt of effective cancer therapies, even when comorbidity and risk of recurrence are taken into account. Information regarding treatment effectiveness in this age group and tools that allow physicians and patients to estimate the benefits versus the risks of therapies, taking into account age and comorbidity burden, are critically needed.
Overlapping and Distinct Expression of Progesterone Receptors A and B in Mouse Uterus and Mammary Gland during the Estrous Cycle
Authors: Mote Patricia A. , Arnett-Mansfield Rebecca L. , Gava Natalie , deFazio Anna , Mulac-Jericevic Biserka , Conneely Orla M. , Clarke Christine L.
Published: September 2006

In rodents, progesterone receptors (PRs) A and B have different and often nonoverlapping roles, and this study asked whether different activities of the PR proteins in mouse are related to differences in their expression in reproductive tissues. The individual expression of PRA and PRB was determined immunohistochemically in mammary gland and uterus during the estrous cycle or in response to endocrine manipulation. In the mammary gland, PRA and PRB were colocated in PR+ epithelial cells, with little change during the estrous cycle. In the uterus, PRA was not detected in luminal epithelium at any stage of the cycle, and PR+ luminal cells expressed only PRB. In the stroma and myometrium, PRA and PRB levels fluctuated with cyclical systemic hormone exposure. Observation of functional end points suggested that augmented stromal and/or myometrial PRA in proestrus inhibited estrogen receptor expression and epithelial proliferation. Colocation of PRA and PRB was hormonally regulated, and ovariectomy did not reproduce the expression of PRA and PRB in the uterus during the estrous cycle. Whereas PRB was the only PR in the luminal epithelium in cycling mice, ovariectomy restored PRA expression, resulting in PRA-PRB colocation. In stroma and myometrium, PRA and PRB colocated in PR+ cells, but ovariectomy reduced PRA levels more than PRB, resulting in PRB-only-expressing cells. This study has shown that nonoverlapping PRA and PRB expression in the uterus, in particular the lack of PRA, and expression of PRB only in the luminal epithelium throughout the estrous cycle, is likely to contribute to the distinct roles of PRA and PRB in the adult mouse.
Improved Metabolic Stimulus for Glucose-Induced Insulin Secretion through GK and PFK-2/FBPase-2 Coexpression in Insulin-Producing RINm5F Cells
Authors: Baltrusch Simone , Langer Sara , Massa Laura , Tiedge Markus , Lenzen Sigurd
Published: September 2006

The glucose sensor enzyme glucokinase plays a pivotal role in the regulation of glucose-induced insulin secretion in pancreatic β-cells. Activation of glucokinase represents a promising concept for the treatment of type 2 diabetes. Therefore, we analyzed the glucokinase activation through its physiological interaction partner, the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) and the resulting effect on glucose metabolism in insulin-producing cells. In RINm5F-GK-PFK-2/FBPase-2 cells stably overexpressing glucokinase plus islet PFK-2/FBPase-2, colocalization between both enzymes as well as elevation of glucokinase activity were significantly increased at a stimulatory glucose concentration of 10 mmol/liter. RINm5F-GK-PFK-2/FBPase-2 cells showed under this culture condition a significant increase in glucose utilization and in the ATP/ADP ratio compared with RINm5F-GK cells, which only overexpress glucokinase. Also glucose-induced insulin secretion was elevated in RINm5F-GK-PFK-2/FBPase-2 cells in comparison to RINm5F-GK cells. Furthermore, pyruvate accumulation and lactate production in RINm5F-GK-PFK-2/FBPase-2 cells were significantly lower at both 10 and 30 mmol/liter glucose than in RINm5F-GK and RINm5F cells. The significant improvement of glucose metabolism after PFK-2/FBPase-2 overexpression is apparently not exclusively the result of high glucokinase enzyme activity. Stabilization of the closed glucokinase conformation by PFK-2/FBPase-2 may not only activate the enzyme but also improve metabolic channeling in β-cells.
Activation of Endothelial Nitric Oxide Synthase by the Angiotensin II Type 1 Receptor
Authors: Suzuki Hiroyuki , Eguchi Kunie , Ohtsu Haruhiko , Higuchi Sadaharu , Dhobale Sudhir , Frank Gerald D. , Motley Evangeline D. , Eguchi Satoru
Published: September 2006

Enhanced angiotensin II (AngII) action has been implicated in endothelial dysfunction that is characterized as decreased nitric oxide availability. Although endothelial cells have been reported to express AngII type 1 (AT1) receptors, the exact role of AT1 in regulating endothelial NO synthase (eNOS) activity remains unclear. We investigated the possible regulation of eNOS through AT1 in bovine aortic endothelial cells (BAECs) and its functional significance in rat aortic vascular smooth muscle cells (VSMCs). In BAECs infected with adenovirus encoding AT1 and in VSMCs infected with adenovirus encoding eNOS, AngII rapidly stimulated phosphorylation of eNOS at Ser1179. This was accompanied with increased cGMP production. These effects were blocked by an AT1 antagonist. The cGMP production was abolished by a NOS inhibitor as well. To explore the importance of eNOS phosphorylation, VSMCs were also infected with adenovirus encoding S1179A-eNOS. AngII did not stimulate cGMP production in VSMCs expressing S1179A. However, S1179A was able to enhance basal NO production as confirmed with cGMP production and enhanced vasodilator-stimulated phosphoprotein phosphorylation. Interestingly, S1179A prevented the hypertrophic response similar to wild type in VSMCs. From these data, we conclude that the AngII/AT1 system positively couples to eNOS via Ser1179 phosphorylation in ECs and VSMCs if eNOS and AT1 coexist. However, basal level NO production may be sufficient for prevention of AngII-induced hypertrophy by eNOS expression. These data demonstrate a novel molecular mechanism of eNOS regulation and function and thus provide useful information for eNOS gene therapy under endothelial dysfunction.
McCune-Albright Syndrome and Acromegaly: Effects of Hypothalamopituitary Radiotherapy and/or Pegvisomant in Somatostatin Analog-Resistant Patients
Authors: Galland Françoise , Kamenicky Peter , Affres Hélène , Reznik Yves , Pontvert Dominique , Le Bouc Yves , Young Jacques , Chanson Philippe
Published: September 2006

Background: Acromegaly, which may be present in patients with McCune-Albright syndrome (MCAS), in association with café-au-lait spots, precocious puberty, and fibrous dysplasia, is often difficult to treat surgically because skull base bone dysplasia prevents the removal of the pituitary adenoma. Somatostatin analogs (SAs) generally give only partial responses. The use of radiotherapy (RT) is controversial because of a possible risk of bone sarcomatous transformation.

Aim: This study was a retrospective analysis of the efficacy and adverse effects of different treatment modalities in six patients with both MCAS and acromegaly.

Patients and Methods: Because surgery was impossible and SA failed to normalize GH/IGF-I hypersecretion, five of the six patients received fractionated RT (45–55 Grays). Three patients (two with previous RT) were also prescribed pegvisomant. We analyzed the clinical features of acromegaly, GH, and IGF-I concentrations and bone radiological features.

Results: GH and IGF-I concentrations fell after RT (median follow-up, 5 yr; range, 0.5–9 yr). Symptoms of acromegaly improved in parallel. Bone sarcomatous transformation was only noted in one patient in a region (the mandible) outside the radiation field. RT alone and/or combined with SA failed to normalize GH/IGF-I levels in the five patients concerned. In contrast, IGF-I levels normalized very rapidly (5–9 months) in the three patients receiving pegvisomant (10–20 mg/d).

Conclusion: RT may be an option for the treatment of acromegaly in patients with MCAS when surgery is impossible and SA therapy is ineffective. However, although no bone sarcomatous transformation was observed within the radiation field in this series, this risk cannot be ruled out. As shown in this small series of severely affected patients, pegvisomant therapy may thus be useful to normalize IGF-I levels rapidly.
Four Novel Missense Mutations in the CYP21A2 Gene Detected in Russian Patients Suffering from the Classical Form of Congenital Adrenal Hyperplasia: Identification, Functional Characterization, and Structural Analysis
Authors: Grischuk Yulia , Rubtsov Petr , Riepe Felix G. , Grötzinger Joachim , Beljelarskaia Svetlana , Prassolov Vladimir , Kalintchenko Natalya , Semitcheva Tatyana , Peterkova Valentina , Tiulpakov Anatoly , Sippell Wolfgang G. , Krone Nils
Published: September 2006

Context: Congenital adrenal hyperplasia is a group of autosomal recessive inherited disorders of steroidogenesis. The most frequent cause is the deficiency of steroid 21-hydroxylase (CYP21) due to mutations in the CYP21A2 gene.

Objective: We analyzed the functional and structural consequences of the four CYP21A2 missense mutations (C169R, G178R, W302R, and R426C) to prove their clinical relevance and study their impact on CYP21 function.

Results: Analyzing the mutations in vitro revealed an almost absent or negligible CYP21 activity for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone. Protein translation and intracellular localization were not affected by the mutants, as could be demonstrated by Western blotting and immunofluorescence studies. Analysis of these mutants in a three-dimensional model structure of the CYP21 protein explained the observed in vitro effects because all the mutations severely interfere either directly or indirectly with important structures of the 21-hydroxylase protein.

Conclusion: The in vitro expression analysis of residual enzyme function is a complementary method to genotyping and an important tool for improving the understanding of the clinical phenotype of 21-hydroxylase deficiency. This forms the foundation for accurate clinical and genetic counseling and for prenatal diagnosis and treatment. Moreover, this report demonstrates that the combination of in vitro enzyme analysis and molecular modeling can yield novel insights into CYP450 structure-functional relationships.
Marked Difference in the Reaction Rate of an Azobenzene-based Photochromic Amorphous Molecular Material between Films Prepared by Vacuum Deposition and Spin Coating
Authors: Tanino Takahiro , Nakano Hideyuki , Shirota Yasuhiko
Published: September 2006

A marked difference in the reaction rate of an azobenzene-based photochromic amorphous molecular material between films prepared by vacuum deposition and spin coating was found, the rate for the vacuum-deposited film being significantly faster compared to spin-coated amorphous film; this result indicates that the microstructures of amorphous films prepared by the above two methods are different from each other, suggesting that the local free volume of the vacuum-deposited film is smaller than that of the spin-coated film.
Analysis of Molecular Aggregation States in Pentacene Thin Films Prepared from Soluble Precursor
Authors: Akinaga Takahiro , Yasutake Shigekazu , Sasaki Sono , Sakata Osami , Otsuka Hideyuki , Takahara Atsushi
Published: September 2006

Molecular packing structure in pentacene films prepared from the Afzali’s precursor soluble in general organic solvents was characterized by in-plane grazing-incidence X-ray diffraction (GIXD) measurements. The crystallographic ab plane of pentacene was parallel to the surface of a Si substrate. Crystal structure of pentacene near the substrate was identified as the thin-film phase.
A New Physiologically Based Pharmacokinetic Analysis for In Vivo Organ Disposition of Nitroxyl Spin Probes in Mice as Measured by Multisite Detection L-band ESR (MSD-LESR)
Authors: Kamatari Masayuki , Yasui Hiroyuki , Nakamura Masahiro , Ogata Tateaki , Sakurai Hiromu
Published: September 2006

We developed a physiologically based pharmacokinetic (PB-PK) model for spin-labeled drugs in animals and applied it for analyzing the decay curves of spin probes in the organs of mice as measured by multisite detection L-band ESR (MSD-LESR). The proposed method will be useful for not only understanding the PK features of nitroxyl radicals as spin probes but also developing spin-labeled drugs as a substitute for radioisotope-labeled drugs.
Training Opportunities in the Management of Paediatric Fractures: A District General Hospital Perspective
Authors: Kim WY , Zenios M
Published: September 2006

INTRODUCTION

Increasing subspecialisation, the introduction of reforms to surgical training, centralisation of hospitals and the reduction of working hours brought about by the European Working Time Directive (EWTD) has direct implications on the training of surgeons in the UK. The aim of this study was to determine the range and number of procedures performed for paediatric orthopaedic fractures, degree of supervision and possible implications for training.

PATIENTS AND METHODS

A retrospective review of procedures for paediatric orthopaedic fractures performed in a district general hospital in a year was conducted.

RESULTS

A total of 210 paediatric fracture procedures were performed, including 99 distal radius/ulna procedures, 28 shaft radius/ulna, 25 supracondylar procedures, 15 hand fracture procedures, 14 tibial shaft procedures. Middle grade/registrars and senior house officers performed 188 (89.5%) of all procedures. Consultant supervision was documented in 29 (13.8%) of all procedures performed. The number and type of common, as well as unusual, injuries was documented. The educational value of a training post may only be confirmed by reliable data which would provide an indication of operative opportunities and degree of supervision available to a trainee.

CONCLUSIONS

This study provided a model upon which all operative training opportunities in the orthopaedic department is documented. It is suggested that such data should form the basis of the establishment of training posts within a region. To maintain the high standard of orthopaedic training in the UK, the maintenance of such posts, number of trainees and seniority of trainees appointed to any hospital within a training region should be on the basis of data such as reported in this study.
Setting the Standard – UK Neurosurgical Acoustic Neuroma Practice
Authors: Goodden JR , Tranter R , Hardwidge C
Published: September 2006

INTRODUCTION

The aim of this study was to determine how current practice in the UK and Ireland complies with the Clinical Effectiveness Guidelines for the Management of Acoustic Neuromas.

MATERIALS AND METHODS

A survey of units and consultants using a standardised questionnaire was carried out.

RESULTS

Fifty-six neurosurgeons treat acoustic neuromas in 33 out of 34 units. In 27 units, one or two surgeons specialise in this area. Caseload per annum per surgeon ranged from 2 to 30, median 15. Forty-one neurosurgeons (75%) work with an ENT surgeon. All surgeons use facial nerve monitoring during surgery. All neurosurgeons informed patients about stereotactic radiosurgery, tending to recommend it for medically unfit patients, and those with small tumours.

CONCLUSIONS

Overall, 26 units (79%) and 40 surgeons (73%) met the criteria for good surgical practice. The main reasons for non-compliance were a lack of teamwork with ENT, and insufficient caseload to maintain surgical expertise.
Medullary Thyroid Carcinoma – Update and Present Management Controversies
Authors: Al-Rawi Mahir , Wheeler Malcolm H
Published: September 2006

INTRODUCTION

Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy arising from the parafollicular C cells. It accounts for 5–10% of thyroid malignancies and occurs in sporadic and hereditary forms. There are still many controversial aspects relating to the diagnosis and management of this unusual tumour in its various forms. The present article addresses the more important of these issues.

METHODS

A literature review was performed using Pubmed database combined with additional original papers obtained from citations in those articles identified in the original literature search. Only those articles which related specifically to the controversial issues addressed in this review were included.

RESULTS

Genetically determined tumours constitute approximately 25% of MTC and have special clinical interest because of their association with other endocrinopathies including phaeochromocytoma and hyperparathyroidism in the multiple endocrine neoplasia syndromes (MEN IIa and MEN IIb). Familial medullary thyroid carcinoma (FMTC) is a rare form not associated with any other endocrinopathies. The genetic basis for these familial tumours derives from a series of missense germline mutations in the RET proto-oncogene. Genetic testing by DNA analysis facilitates identification of family members at risk who can now be offered early ‘prophylactic thyroidectomy’ with an increased prospect of surgical success and long-term survival. MTC is a tumour which does not take up radioactive iodine, is relatively radioresistant and poorly responsive to chemotherapy. Therefore, surgery is the only treatment which can offer the prospect of cure. Total thyroidectomy with central and lateral nodal dissection can achieve biochemical cure (normocalcitonaemia) in more than 80% of cases. Compartmental orientated microdissection of cervical nodes has significantly improved the results of primary surgery but even so a group of 20% of patients will prove to have recurrent or residual disease. These cases require detailed investigation by a variety of techniques including ultrasound, cross-sectional imaging, nuclear imaging and laparoscopy with liver biopsy to exclude disseminated disease and select those patients who can be offered a prospect of cure by further neck surgery. Such an approach may be associated with successful normalisation of calcitonin levels in about 40%.

CONCLUSIONS

It is hoped that in the near future new medical therapies may become available to treat MTC which still has a 10-year survival of only 60–80% in spite of the application of meticulous surgical techniques.
Systematic Review of Medication Errors in Pediatric Patients
Authors: Ghaleb Maisoon Abdullah , Barber Nick , Franklin Bryony D , Yeung Vincent WS , Khaki Zahra F , Wong Ian CK
Published: September 2006

Objective:

To systematically locate and review studies that have investigated the incidence of medication errors (MEs) in pediatric inpatients and identify common errors.

Methods:

A systematic search of studies related to MEs in children was performed using the following databases: MEDLINE (1951–April 2006), EMBASE (1966–April 2006), Pharm-line (1978–April 2006), International Pharmaceutical Abstracts (1970–April 2006), Cumulative Index to Nursing and Allied Health Literature (1982–April 2006), and British Nursing Index (1994–April 2006). Studies of the incidence and nature of MEs in pediatrics were included. The title, abstract, or full article was reviewed for relevance; any study not related to MEs in children was excluded.

Results:

Three methods were used to detect MEs in the studies reviewed: spontaneous reporting (n = 10), medication order or chart review (n = 14), or observation (n = 8). There was great variation in the definitions of ME used and the error rates reported. The most common type of ME was dosing error, often involving 10 times the actual dose required. Antibiotics and sedatives were the most common classes of drugs associated with MEs; these are probably among the most common drugs prescribed.

Conclusions:

Interpretation of the literature was hindered by variation in definitions employed by different researchers, varying research methods and setting, and a lack of theory-based research. Overall, it would appear that our initial concern about MEs in pediatrics has been validated; however, we do not know the actual size of the problem. Further work to determine the incidence and causes of MEs in pediatrics is urgently needed, as well as evaluation of the best interventions to reduce them.
Formulary Forum: Exenatide: A New Option for the Treatment of Type 2 Diabetes
Authors: Yoo Bong Kyu , Triller Darren Michael , Yoo Dong Joo
Published: September 2006

Objective:

To evaluate available literature characterizing the pharmacology, pharmacokinetics, drug interactions, efficacy, and safety of exenatide in patients with type 2 diabetes.

Data Sources:

A PubMed database search (1966–May 2006) was conducted, using exenatide as the search term. The manufacturer's prescribing information was also used.

Study Selection and Data Extraction:

English-language articles were selected and data were extracted with a focus on clinical outcomes associated with the treatment of patients with type 2 diabetes.

Data Synthesis:

Exenatide exerts a glucoregulatory effect by various mechanisms including secretion of glucose-dependent insulin, suppression of inappropriately high glucagon levels in patients with type 2 diabetes, delayed gastric emptying, and reduction of food intake. In placebo-controlled clinical studies, plasma exenatide concentrations appeared to exhibit dose-proportional kinetics, reaching peak plasma levels between 2 and 3 hours after a single subcutaneous injection. Exenatide's elimination half-life ranged from 3.3 to 4.0 hours, and the time to reach maximum concentration was about 2 hours. Interactions between exenatide and agents such as digoxin and lisinopril were not considered significant. In Phase III trials, exenatide demonstrated significant reduction of hemoglobin A1c levels from baseline and compared with placebo after 30 weeks of treatment in patients unable to achieve optimal glycemic control with metformin, a sulfonylurea, or oral combination therapy (0.4–0.9%). Patients' weight decreased with exenatide (0.9–2.8 kg), but adverse gastrointestinal (GI) events were common. Exenatide combined with thiazolidonediones, D-phenylalanine derivatives, meglitinides, or alpha glucosidase inhibitors has not been studied.

Conclusions:

Clinical trials have demonstrated that exenatide improves glycemic control when added to sulfonylureas and metformin, and it may be an alternative to insulin glargine in patients requiring additional therapy. Hypoglycemia has been encountered in clinical trials of exenatide, especially upon initiation of therapy with sulfonylureas (not with metformin); close patient monitoring is therefore recommended. Further studies should assess the impact of exenatide on clinical outcomes such as micro- and macrovascular disease.
Predicting behaviour towards genetically modified food using implicit and explicit attitudes
Authors: Spence Alexa , Townsend Ellen
Published: September 2006

The predictive validity of implicit and explicit attitudes is a central question in social psychological research with important theoretical and empirical ramifications. Three main patterns of combining implicit and explicit attitudes to predict behaviour have been postulated. They are, double dissociation (in which implicit and explicit attitudes predict spontaneous and deliberate behaviour respectively), additive (in which implicit and explicit attitudes both predict variance in behaviour) and interactive (in which implicit and explicit attitudes combine to predict behaviour). These models were tested in this study using a structural equation modelling approach utilising three different measures of behaviour (of varying spontaneity) towards genetically modified (GM) food. The additive pattern, in which implicit and explicit attitudes both predict variance in behaviour, was found to best fit the data. In addition, all behaviour measures indicated that the majority of participants were willing to try GM food in some situations.
Hole-Enhanced Raman Scattering
Authors: Bahns John T. , Yan Funing , Qiu Dengli , Wang Rong , Chen Liaohai
Published: September 2006

Stokes and anti-Stokes non-resonant hole-enhanced Raman scattering (HERS) spectra with high signal-to-noise ratio (S/N) are reported for the first time for aqueous phase R6G molecules adsorbed onto random nanoholes in thin gold films. Compared to conventional surface-enhanced Raman scattering from nanometric gold colloid particles, HERS exhibits higher strength gain, exceptional reproducibility, simple and reliable substrate preparation, and excellent mechanical stability. By correlating the hole density with Raman scattering gain, we determined optimum HERS gain for 50 nm diameter holes at ∼100 holes/μm2. Providing a Raman substrate with uniform “hot spots”, we expect that HERS will make the quantitative Raman analysis of biological molecules possible.
Nonlinear Forward Scattering in Cesium Vapor: Experiment with Simultaneous Scanning of Laser Frequency and B-Field
Authors: Papoyan A. V. , Gazazyan E. A.
Published: September 2006

We present the results of an experimental study of nonlinear magneto-optical rotation in a buffer-gas-free uncoated Cs cell on hyperfine transitions Fg = 3 → Fe = 2, 3, 4 of the D2 line at high laser irradiance (up to 40 mW/cm2). The measurements were done in a forward scattering configuration, with simultaneous linear scanning of laser frequency and magnetic field at different temporal rates. The latter revealed, in a single measurement, the dependences of maximum nonlinear Faraday signal and the corresponding B-field on the laser frequency within the Doppler profile.
Water Evaporation Analysis of L-Phenylalanine from Initial Aqueous Solutions to Powder State by Vibrational Spectroscopy
Authors: Olsztynska S. , Dupuy N. , Vrielynck L. , Komorowska M.
Published: September 2006

The water evaporation from L-phenylalanine (L-phe) aqueous solutions at different initial pH (0–13) was studied by vibrational spectroscopy. Next, the attenuated total reflection–Fourier transform infrared (ATR-FT-IR) spectra of aqueous solutions were compared to those recorded after drying for 72 h at 21 °C at appropriate initial pH values. Micro-Raman results collected after the water evaporation process are also presented and interpreted. Between pH = 2.5 and 8.76 a white non-transparent gel was observed, possibly due to the presence of the NaCl salt. The significant differences of the band intensities of L-phe functional groups noticed at pH near p Ka values indicate the structural changes of L-phe molecules due to dimer formation (hydrogen bonds between the –COOH and –CO2− groups, and the –NH3+ and –NH2 groups). The presence of the hydrophobic interactions leads to the aggregation of L-phe molecules, most probably via phe–phe stacking as well as complexes of phe with Na+ ions, HCl, or H2O molecules.
A Study on Water Adsorption onto Microcrystalline Cellulose by Near-Infrared Spectroscopy with Two-Dimensional Correlation Spectroscopy and Principal Component Analysis
Authors: Watanabe Akihiko , Morita Shigeaki , Ozaki Yukihiro
Published: September 2006

Water adsorption onto microcrystalline cellulose (MCC) in the moisture content ( Mc) range of 0.2–13.4 wt % was investigated by near-infrared (NIR) spectroscopy. In order to distinguish heavily overlapping O–H stretching bands in the NIR region due to MCC and water, principal component analysis (PCA) and generalized two-dimensional correlation spectroscopy (2DCOS) were applied to the obtained spectra. The NIR spectra in four adsorption stages separated by PCA were analyzed by 2DCOS. For the low Mc range of 0.2–3.1 wt %, a decrease in the free or weakly hydrogen-bonded (H-bonded) MCC OH band, increases in the H-bonded MCC OH bands, and increases in the adsorbed water OH bands are observed. These results suggest that the inter- and intrachain H-bonds of MCC are formed by monomeric water molecule adsorption. In the Mc range of 3.8–7.1 wt %, spectral changes in the NIR spectra reveal that the aggregation of water molecules starts at the surface of MCC. For the high Mc range of 8.1–13.4 wt %, the NIR results suggest that the formation of bulk water occurs. It is revealed from the present study that approximately 3–7 wt % of adsorbed water is responsible for the stabilization of the H-bond network in MCC at the cellulose–water surface.
Surface Plasmon Resonance Investigations of Human Epidermal Growth Factor Receptor 2
Authors: Martin V. S. , Sullivan B. A. , Walker K. , Hawk H. , Sullivan B. P. , Noe L. J.
Published: September 2006

This investigation utilizes surface plasmon resonance (SPR) spectroscopy to detect and quantify human epidermal growth factor receptor 2 (HER-2), an oncogene product that is over-expressed in some aggressive forms of breast cancer. Specifically, the HER-2 trans-membrane protein p185 and its extra cellular fragment p105 are analytes targeted in this work by using a gold-based biosensor slide on which an anti-HER-2 antibody has been immobilized by attachment to Protein G that is fixed to the gold film. A detection limit of ≥11 ng/mL for p185 resulted when trastuzumab was used as the anti-HER-2 antibody on the biosensor slide. Experiments with semi-purified p105 revealed that it binds weakly and reversibly to trastuzumab, therefore complicating its detection and quantification. Results of studies that reacted a 13-amino-acid peptide (PP13) from the HER-2 kinase domain with its specific antibody were critically different than p185 and p105 studies. Spectral analysis of the reflectivity at constant bulk buffer refractive index revealed a progressive negative SPR shift over time. A negative shift suggests that a loss of protein mass from the anti-PP13 antibody–Protein G biosensor is occurring. Several possibilities that may explain these negative SPR shifts are discussed.
Use of Artificial Neural Networks in Near-Infrared Reflectance Spectroscopy Calibrations for Predicting the Inclusion Percentages of Wheat and Sunflower Meal in Compound Feedingstuffs
Authors: Pérez-Marín D. , Garrido-Varo A. , Guerrero J. E. , Gutiérrez-Estrada J. C.
Published: September 2006

The use of near-infrared reflectance spectroscopy (NIRS) calibrations to predict the ingredient composition in compound feeds (i.e., inclusion percentage of each ingredient) is a complex task, regarding both the nature of the parameters to be predicted, since they are not well-defined chemical entities, and the heterogeneousness of the matrices/formulas in which each ingredient participates. The present paper evaluates the use of nonlinear regression methods, such as artificial neural networks (ANN), for developing NIRS calibrations to predict these parameters. Two of the most representative ingredients in the Spanish compound feed formulations (wheat and sunflower meal) were selected for evaluating ANN possibilities, using a large spectral library comprising a total of 7523 commercial compound feed samples; 7423 were used as training set and 100 as validation set. Three general models of networks were studied: multilayer perceptron with back-propagation training (BP), multilayer perceptron with Levenberg–Maquartd training (LM), and radial basis function nets (RBF); moreover, in accordance with a factorial design, more complex architectures were evaluated gradually, changing the number of hidden layers and hidden neurons, for the determination of the optimal network topology. For both ingredients, the best results were obtained using ANN with BP training, showing prediction error values (SEP) of 2.72% and 0.66% for wheat and sunflower meal, respectively. These SEP values showed a significant improvement (19%–49% for sunflower meal and wheat, respectively) in comparison with those obtained using calibrations developed with linear methods.
Social capital in contemporary Europe: evidence from the European Social Survey
Authors: Halman Loek , Luijkx Ruud
Published: September 2006

Social capital is an increasingly popular concept among scientists, politicians and the media. It is regarded as a remedy for many of the failures of modern society and seen as wonder glue conducive to feelings of happiness and to better performing economies and democracies. In this article we are not so much concerned with the consequences of social capital for society, but we focus on why some people have higher levels of social capital than others. We argue that this is not only due to a number of personal characteristics but also to contextual or country features. We therefore formulate hypotheses about the effects of individual and macro or country characteristics that were tested using the survey data from the European Social Survey (2002). The results demonstrate that the impact of macro characteristics is rather modest compared to the effects of individual attributes. It also seems that social capital is a multifaceted phenomenon that cannot be captured by one single measure.
Identification of Sox17 as a Transcription Factor That Regulates Oligodendrocyte Development
Authors: Sohn Jiho , Natale JoAnne , Chew Li-Jin , Belachew Shibeshih , Cheng Ying , Aguirre Adan , Lytle Judith , Nait-Oumesmar Brahim , Kerninon Christophe , Kanai-Azuma Masami , Kanai Yoshiakira , Gallo Vittorio
Published: September 2006

Microarray analysis of oligodendrocyte lineage cells purified by fluorescence-activated cell sorting (FACS) from 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP)–enhanced green fluorescent protein (EGFP) transgenic mice revealed Sox17 (SRY-box containing gene 17) gene expression to be coordinately regulated with that of four myelin genes during postnatal development. In CNP–EGFP-positive (CNP–EGFP+) cells, Sox17 mRNA and protein levels transiently increased between postnatal days 2 and 15, with white matter O4+preoligodendrocytes expressing greater Sox17 levels than Nkx2.2+(NK2 transcription factor related, locus 2) NG2+, or GalC+(galactocerebroside) cells. In spinal cord, Sox17 protein expression was undetectable in the primary motor neuron domain between embryonic days 12.5 and 15.5 but was evident in Nkx2.2+and CC1+cells. In cultured oligodendrocyte progenitor cells (OPCs), Sox17 levels were maximal in O4+cells and peaked during the phenotypic conversion from bipolar to multipolar. Parallel increases in Sox17 and p27 occurred before MBP protein expression, and Sox17 upregulation was prevented by conditions inhibiting differentiation. Sox17 downregulation with small interfering RNAs increased OPC proliferation and decreased lineage progression after mitogen withdrawal, whereas Sox17 overexpression in the presence of mitogen had opposite effects. Sox17 overexpression enhanced myelin gene expression in OPCs and directly stimulated MBP gene promoter activity. These findings support important roles for Sox17 in controlling both oligodendrocyte progenitor cell cycle exit and differentiation.