bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores
Authors: Wood John C. , Kang Barinder P. , Thompson Alexis , Giardina Patricia , Harmatz Paul , Glynos Tara , Paley Carole , Coates Thomas D.
Published: April 2010

We present results from a prospective, multicenter, open-label, single-arm study evaluating response of cardiac and liver iron to deferasirox therapy for 18 months. Twenty-eight patients with abnormal T2* and normal left ventricular ejection fraction were enrolled from 4 US centers. All patients initially received deferasirox doses of 30 to 40 mg/kg per day. Patients were severely iron overloaded: mean liver iron concentration (LIC) 20.3 mg Fe/g dry weight, serum ferritin 4417 ng/mL, and cardiac T2* 8.6 ms. In the intent-to-treat population, 48% reached the primary endpoint (cardiac T2* improvement at 18 months, P = not significant). There were 2 deaths: 1 from congestive heart failure and 1 from sepsis. In the 22 patients completing the trial, LIC and cardiac T2* improvements were 16% (P = .06) and 14% (P = .07), respectively. Cardiac T2* improvement (13 patients) was predicted by initial LIC, final LIC, and percentage LIC change, but not initial cardiac T2*. Cardiac iron improved 24% in patients having LIC in the lower 2 quartiles and worsened 8.7% in patients having LIC in the upper 2 quartiles. Left ventricular ejection fraction was unchanged at all time points. Monotherapy with deferasirox was effective in patients with mild to moderate iron stores but failed to remove cardiac iron in patients with severe hepatic iron burdens. This study was registered at www.clinicaltrials.gov as #NCT00447694.
Evolution of the MAGUK protein gene family in premetazoan lineages
Authors: de Mendoza Alex , Suga Hiroshi , Ruiz-Trillo Iñaki
Published: April 2010

Background

Cell-to-cell communication is a key process in multicellular organisms. In multicellular animals, scaffolding proteins belonging to the family of membrane-associated guanylate kinases (MAGUK) are involved in the regulation and formation of cell junctions. These MAGUK proteins were believed to be exclusive to Metazoa. However, a MAGUK gene was recently identified in an EST survey of Capsaspora owczarzaki, an unicellular organism that branches off near the metazoan clade. To further investigate the evolutionary history of MAGUK, we have undertook a broader search for this gene family using available genomic sequences of different opisthokont taxa.

Results

Our survey and phylogenetic analyses show that MAGUK proteins are present not only in Metazoa, but also in the choanoflagellate Monosiga brevicollis and in the protist Capsaspora owczarzaki. However, MAGUKs are absent from fungi, amoebozoans or any other eukaryote. The repertoire of MAGUKs in Placozoa and eumetazoan taxa (Cnidaria + Bilateria) is quite similar, except for one class that is missing in Trichoplax, while Porifera have a simpler MAGUK repertoire. However, Vertebrata have undergone several independent duplications and exhibit two exclusive MAGUK classes. Three different MAGUK types are found in both M. brevicollis and C. owczarzaki: DLG, MPP and MAGI. Furthermore, M. brevicollis has suffered a lineage-specific diversification.

Conclusions

The diversification of the MAGUK protein gene family occurred, most probably, prior to the divergence between Metazoa+choanoflagellates and the Capsaspora+Ministeria clade. A MAGI-like, a DLG-like, and a MPP-like ancestral genes were already present in the unicellular ancestor of Metazoa, and new gene members have been incorporated through metazoan evolution within two major periods, one before the sponge-eumetazoan split and another within the vertebrate lineage. Moreover, choanoflagellates have suffered an independent MAGUK diversification. This study highlights the importance of generating enough genome data from the broadest possible taxonomic sampling, in order to fully understand the evolutionary history of major protein gene families.
Global transcriptome analysis of spore formation in Myxococcus xanthus reveals a locus necessary for cell differentiation
Authors: Müller Frank-Dietrich , Treuner-Lange Anke , Heider Johann , Huntley Stuart M , Higgs Penelope I
Published: April 2010

Background

Myxococcus xanthus is a Gram negative bacterium that can differentiate into metabolically quiescent, environmentally resistant spores. Little is known about the mechanisms involved in differentiation in part because sporulation is normally initiated at the culmination of a complex starvation-induced developmental program and only inside multicellular fruiting bodies. To obtain a broad overview of the sporulation process and to identify novel genes necessary for differentiation, we instead performed global transcriptome analysis of an artificial chemically-induced sporulation process in which addition of glycerol to vegetatively growing liquid cultures of M. xanthus leads to rapid and synchronized differentiation of nearly all cells into myxospore-like entities.

Results

Our analyses identified 1 486 genes whose expression was significantly regulated at least two-fold within four hours of chemical-induced differentiation. Most of the previously identified sporulation marker genes were significantly upregulated. In contrast, most genes that are required to build starvation-induced multicellular fruiting bodies, but which are not required for sporulation per se, were not significantly regulated in our analysis. Analysis of functional gene categories significantly over-represented in the regulated genes, suggested large rearrangements in core metabolic pathways, and in genes involved in protein synthesis and fate. We used the microarray data to identify a novel operon of eight genes that, when mutated, rendered cells unable to produce viable chemical- or starvation-induced spores. Importantly, these mutants displayed no defects in building fruiting bodies, suggesting these genes are necessary for the core sporulation process. Furthermore, during the starvation-induced developmental program, these genes were expressed in fruiting bodies but not in peripheral rods, a subpopulation of developing cells which do not sporulate.

Conclusions

These results suggest that microarray analysis of chemical-induced spore formation is an excellent system to specifically identify genes necessary for the core sporulation process of a Gram negative model organism for differentiation.
Pseudomonas aeruginosa inhibits in-vitro Candida biofilm development
Authors: Bandara HMHN , Yau JYY , Watt RM , Jin LJ , Samaranayake LP
Published: April 2010

Background

Elucidation of the communal behavior of microbes in mixed species biofilms may have a major impact on understanding infectious diseases and for the therapeutics. Although, the structure and the properties of monospecies biofilms and their role in disease have been extensively studied during the last decade, the interactions within mixed biofilms consisting of bacteria and fungi such as Candida spp. have not been illustrated in depth. Hence, the aim of this study was to evaluate the interspecies interactions of Pseudomonas aeruginosa and six different species of Candida comprising C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. dubliniensis in dual species biofilm development.

Results

A significant reduction in colony forming units (CFU) of C. parapsilosis (90 min), C. albicans and C. tropicalis (90 min, 24 h and 48 h), C. dubliniensis and C. glabrata, (24 h and 48 h) was noted when co-cultured with P. aeruginosa in comparison to their monospecies counterparts (P < 0.05). A simultaneous significant reduction in P. aeruginosa numbers grown with C. albicans (90 min and 48 h), C. krusei (90 min, 24 h and 48 h),C. glabrata, (24 h and 48 h), and an elevation of P. aeruginosa numbers co-cultured with C. tropicalis (48 h) was noted (P < 0.05). When data from all Candida spp. and P. aeruginosa were pooled, highly significant mutual inhibition of biofilm formation was noted (Candida P < 0.001, P. aeruginosa P < 0.01). Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) analyses confirmed scanty architecture in dual species biofilm in spite of dense colonization in monospecies counterparts.

Conclusions

P. aeruginosa and Candida in a dual species environment mutually suppress biofilm development, both quantitatively and qualitatively. These findings provide a foundation to clarify the molecular basis of bacterial-fungal interactions, and to understand the pathobiology of mixed bacterial-fungal infections.
Tomato root transcriptome response to a nitrogen-enriched soil patch
Authors: Ruzicka Daniel R , Barrios-Masias Felipe H , Hausmann Natasha T , Jackson Louise E , Schachtman Daniel P
Published: April 2010

Background

Nitrogen (N), the primary limiting factor for plant growth and yield in agriculture, has a patchy distribution in soils due to fertilizer application or decomposing organic matter. Studies in solution culture over-simplify the complex soil environment where microbial competition and spatial and temporal heterogeneity challenge roots' ability to acquire adequate amounts of nutrients required for plant growth. In this study, various ammonium treatments (as15N) were applied to a discrete volume of soil containing tomato (Solanum lycopersicum) roots to simulate encounters with a localized enriched patch of soil. Transcriptome analysis was used to identify genes differentially expressed in roots 53 hrs after treatment.

Results

The ammonium treatments resulted in significantly higher concentrations of both ammonium and nitrate in the patch soil. The plant roots and shoots exhibited increased levels of15N over time, indicating a sustained response to the enriched environment. Root transcriptome analysis identified 585 genes differentially regulated 53 hrs after the treatments. Nitrogen metabolism and cell growth genes were induced by the high ammonium (65 μg NH4+-N g-1soil), while stress response genes were repressed. The complex regulation of specific transporters following the ammonium pulse reflects a simultaneous and synergistic response to rapidly changing concentrations of both forms of inorganic N in the soil patch. Transcriptional analysis of the phosphate transporters demonstrates cross-talk between N and phosphate uptake pathways and suggests that roots increase phosphate uptake via the arbuscular mycorrhizal symbiosis in response to N.

Conclusion

This work enhances our understanding of root function by providing a snapshot of the response of the tomato root transcriptome to a pulse of ammonium in a complex soil environment. This response includes an important role for the mycorrhizal symbiosis in the utilization of an N patch.
Kocuria varians infection associated with brain abscess: A case report
Authors: Tsai Cheng-Yu , Su Shou-hsin , Cheng Yu-Hsin , Chou Yu-lin , Tsai Tai-Hsin , Lieu Ann-Shung
Published: April 2010

Background

Kocuria, established by Stackebrandt et al., previously was classified into Micrococcus. Only two species, K. rosea and K. kristinae are reported to be associated as pathogenic and found with catheter-related bacteremia and acute cholecystitis.

Case presentation

We herein report the first case of brain abscess caused by Kocuria varians, a gram-positive microorganism, in a 52-year-old man. Hematogenous spread is the probable pathogenesis.

Conclusions

This report presents a case of Kocuria varians brain abscess successfully treated with surgical excision combined with antimicrobial therapy. In addition, Vitek 2 system has been used to identify and differentiate between coagulase-negative staphylococcus.
Epidermal growth factor induces HCCR expression via PI3K/Akt/mTOR signaling in PANC-1 pancreatic cancer cells
Authors: Xu Zekuan , Zhang Yi , Jiang Jiakai , Yang Yang , Shi Ruihua , Hao Bo , Zhang Zhihong , Huang Zuhu , Kim Jin W , Zhang Guoxin
Published: April 2010

Background

Human cervical cancer oncoprotein 1 (HCCR-1), reported as a negative regulator of p53, is over-expressed in a variety of human cancers. However, it is yet unknown whether HCCR-1 plays any role in pancreatic cancer development. The aim of this study was to investigate the effect of epidermal growth factor on the expression of HCCR in pancreatic cancer cells, and to explore if PI3K/Akt/mTOR signaling pathway mediated this expression.

Methods

A polyclonal antibody against HCCR protein was raised by immunizing Balb/c mice with the purified recombinant protein pMBPc-HCCR. Tissue samples were constructed on a tissue chip, and the expression of HCCR was investigated by immunohistochemistry assay and Western blotting. Pancreatic cell line, PANC-1 cells were stably transfected with plasmids containing sense-HCCR-1 fragment and HCCR siRNA fragment. MTT and transwell assay were used to investigate the proliferation and invasion of stable tansfectants. The specific inhibitor of PI3K and mTOR was used to see if PI3K/mTOR signal transduction was involved in the induction of HCCR gene expression. A Luciferase assay was used to see if Akt can enhance the HCCR promoter activity.

Results

HCCR was up-regulated in pancreatic tumor tissues (mean Allred score 4.51 ± 1.549 vs. 2.87 ± 2.193, P < 0.01), especially with high expression in poorly differentiated pancreatic cancer. The growth of cells decreased in HCCR-1 siRNA transfected cells compared with vector transfectants. The number of invasion cells was significantly lower in HCCR-1 siRNA transfected cells (24.4 ± 9.9) than that in vector transfectants (49.1 ± 15.4). Treatment of PANC-1 cells with epidermal growth factor increased HCCR protein level in a dose- and time-dependent manner. However, application of LY294002 and rapamycin caused a dramatic reduction of epidermal growth factor-induced HCCR expression. Over-expression of exogenous constitutively active Akt increased the HCCR promoter activity; in contrast, dominant negative Akt decreased the promoter activity.

Conclusions

EGF-induced HCCR-1 over-expression is mediated by PI3K/AKT/mTOR signaling which plays a pivotal role in pancreatic tumor progression, suggesting that HCCR-1 could be a potential target for cancer therapeutics.
Prediction of posttraumatic stress disorder among adults in flood district
Authors: Huang Peng , Tan Hongzhuan , Liu Aizhong , Feng Shuidong , Chen Mengshi
Published: April 2010

Background

Flood is one of the most common and severe forms of natural disasters. Posttraumatic stress disorder (PTSD) is a common disorder among victims of various disasters including flood. Early prediction for PTSD could benefit the prevention and treatment of PTSD. This study aimed to establish a prediction model for the occurrence of PTSD among adults in flood districts.

Methods

A cross-sectional survey was carried out in 2000 among individuals who were affected by the 1998 floods in Hunan, China. Multi-stage sampling was used to select subjects from the flood-affected areas. Data was collected through face-to-face interviews using a questionnaire. PTSD was diagnosed according to DSM-IV criteria. Study subjects were randomly divided into two groups: group 1 was used to establish the prediction model and group 2 was used to validate the model. We first used the logistic regression analysis to select predictive variables and then established a risk score predictive model. The validity of model was evaluated by using the model in group 2 and in all subjects. The area under the receiver operation characteristic (ROC) curve was calculated to evaluate the accuracy of the prediction model.

Results

A total of 2336 (9.2%) subjects were diagnosed as probable PTSD-positive individuals among a total of 25,478 study subjects. Seven independent predictive factors (age, gender, education, type of flood, severity of flood, flood experience, and the mental status before flood) were identified as key variables in a risk score model. The area under the ROC curve for the model was 0.853 in the validation data. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this risk score model were 84.0%, 72.2%, 23.4%, and 97.8%, respectively, at a cut-off value of 67.5 in the validation data.

Conclusions

A simple risk score model can be used to predict PTSD among victims of flood.
Analysis of post-operative changes in serum protein expression profiles from colorectal cancer patients by MALDI-TOF mass spectrometry: a pilot methodological study
Authors: Liao Christopher CL , Mehta Anuja , Ward Nicholas J , Marsh Simon , Arulampalam Tan , Norton John D
Published: April 2010

Background

Mass spectrometry-based protein expression profiling of blood sera can be used to discriminate colorectal cancer (CRC) patients from unaffected individuals. In a pilot methodological study, we have evaluated the changes in protein expression profiles of sera from CRC patients that occur following surgery to establish the potential of this approach for monitoring post-surgical response and possible early prediction of disease recurrence.

Methods

In this initial pilot study, serum specimens from 11 cancer patients taken immediately prior to surgery and at approximately 6 weeks following surgery were analysed alongside 10 normal control sera by matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS). Using a two-sided t-test the top 20 ranked protein peaks that discriminate normal from pre-operative sera were identified. These were used to classify post-operative sera by hierarchical clustering analysis (Spearman's Rank correlation) and, as an independent 'test' dataset, by k-nearest neighbour and weighted voting supervised learning algorithms.

Results

Hierarchical cluster analysis classified post-operative sera from all six early Dukes' stage (A and B) patients as normal. The remaining five post-operative sera from more advanced Dukes' stages (C1 and C2) were classified as cancer. Analysis by supervised learning algorithms similarly grouped all advanced Dukes' stages as cancer, with four of the six post-operative sera from early Dukes' stages being classified as normal (P = 0.045; Fisher's exact test).

Conclusions

The results of this pilot methodological study illustrate the proof-of-concept of using protein expression profiling of post-surgical blood sera from individual patients to monitor disease course. Further validation on a larger patient cohort and using an independent post-operative sera dataset would be required to evaluate the potential clinical relevance of this approach. Prospective data, including follow-up on patient survival, could in the future, then be evaluated to inform decisions on individualised treatment modalities.
On the identification of sensory information from mixed nerves by using single-channel cuff electrodes
Authors: Raspopovic Stanisa , Carpaneto Jacopo , Udina Esther , Navarro Xavier , Micera Silvestro
Published: April 2010

Background

Several groups have shown that the performance of motor neuroprostheses can be significantly improved by detecting specific sensory events related to the ongoing motor task (e.g., the slippage of an object during grasping). Algorithms have been developed to achieve this goal by processing electroneurographic (ENG) afferent signals recorded by using single-channel cuff electrodes. However, no efforts have been made so far to understand the number and type of detectable sensory events that can be differentiated from whole nerve recordings using this approach.

Methods

To this aim, ENG afferent signals, evoked by different sensory stimuli were recorded using single-channel cuff electrodes placed around the sciatic nerve of anesthetized rats. The ENG signals were digitally processed and several features were extracted and used as inputs for the classification. The work was performed on integral datasets, without eliminating any noisy parts, in order to be as close as possible to real application.

Results

The results obtained showed that single-channel cuff electrodes are able to provide information on two to three different afferent (proprioceptive, mechanical and nociceptive) stimuli, with reasonably good discrimination ability. The classification performances are affected by the SNR of the signal, which in turn is related to the diameter of the fibers encoding a particular type of neurophysiological stimulus.

Conclusions

Our findings indicate that signals of acceptable SNR and corresponding to different physiological modalities (e.g. mediated by different types of nerve fibers) may be distinguished.
A formal model for analyzing drug combination effects and its application in TNF-α-induced NFκB pathway
Authors: Yan Han , Zhang Bo , Li Shao , Zhao Qianchuan
Published: April 2010

Background

Drug combination therapy is commonly used in clinical practice. Many methods including Bliss independence method have been proposed for drug combination design based on simulations models or experiments. Although Bliss independence method can help to solve the drug combination design problem when there are only a small number of combinations, as the number of combinations increases, it may not be scalable. Exploration of system structure becomes important to reduce the complexity of the design problem.

Results

In this paper, we deduced a mathematical model which can simplify the serial structure and parallel structure of biological pathway for synergy evaluation of drug combinations. We demonstrated in steady state the sign of the synergism assessment factor derivative of the original system can be predicted by the sign of its simplified system. In addition, we analyzed the influence of feedback structure on survival ratio of the serial structure. We provided a sufficient condition under which the combination effect could be maintained. Furthermore, we applied our method to find three synergistic drug combinations on tumor necrosis factor α-induced NFκB pathway and subsequently verified by the cell experiment.

Conclusions

We identified several structural properties underlying the Bliss independence criterion, and developed a systematic simplification framework for drug combiation desgin by combining simulation and system reaction network topology analysis. We hope that this work can provide insights to tackle the challenging problem of assessment of combinational drug therapy effect in a large scale signaling pathway. And hopefully in the future our method could be expanded to more general criteria.
Duration of First Off-Treatment Interval Is Prognostic for Time to Castration Resistance and Death in Men With Biochemical Relapse of Prostate Cancer Treated on a Prospective Trial of Intermittent Androgen Deprivation
Authors: Yu Evan Y. , Gulati Roman , Telesca Donatello , Jiang Peter , Tam Stephen , Russell Kenneth J. , Nelson Peter S. , Etzioni Ruth D. , Higano Celestia S.
Published: April 2010

Purpose

This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death.

Patients and Methods

Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as ≥ two consecutive increasing PSA values while on ADT with castrate testosterone levels.

Results

Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (≤ v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis.

Conclusion

In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of ≤ 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis.
A Study of Experimental Syringomyelia by Scanning Electron Microscopy
Authors: Hall Peter , Godersky John , Muller Jans , Muller Robert , Kalsbeck John
Published: April 2010

Experimental hydromyelia and syringomyelia, induced by kaolin in dogs, has been investigated by scanning electron microscopy. This study demonstrated that communication between the 4th ventricle and the spinal central canal is normally occluded by a plug of acellular material lying within the central canal. This plug is broken down following the onset of hydrocephalus and communication is rapidly established between the ventricles and the central canal. The canal distends and ruptures dorsally into the spinal gray matter with the development of extensive intramedullary cavities, lined by glial and neuronal elements. The morphological changes demonstrated are consistent with a physical destructive process of the cord resulting from CSF dissection.
Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract
Authors: Mao Junhao , Kim Byeong-Moo , Rajurkar Mihir , Shivdasani Ramesh A. , McMahon Andrew P.
Published: April 2010

Homeostasis of the vertebrate digestive tract requires interactions between an endodermal epithelium and mesenchymal cells derived from the splanchnic mesoderm. Signaling between these two tissue layers is also crucial for patterning and growth of the developing gut. From early developmental stages, sonic hedgehog (Shh) and indian hedgehog (Ihh) are secreted by the endoderm of the mammalian gut, indicative of a developmental role. Further, misregulated hedgehog (Hh) signaling is implicated in both congenital defects and cancers arising from the gastrointestinal tract. In the mouse, only limited gastrointestinal anomalies arise following removal of either Shh or Ihh. However, given the considerable overlap in their endodermal expression domains, a functional redundancy between these signals might mask a more extensive role for Hh signaling in development of the mammalian gut. To address this possibility, we adopted a conditional approach to remove both Shh and Ihh functions from early mouse gut endoderm. Analysis of compound mutants indicates that continuous Hh signaling is dispensable for regional patterning of the gut tube, but is essential for growth of the underlying mesenchyme. Additional in vitro analysis, together with genetic gain-of-function studies, further demonstrate that Hh proteins act as paracrine mitogens to promote the expansion of adjacent mesenchymal progenitors, including those of the smooth muscle compartment. Together, these studies provide new insights into tissue interactions underlying mammalian gastrointestinal organogenesis and disease.
Size effect and forming-limit strain prediction for microscale sheet metal forming of stainless steel 304
Authors: Chen C-H , Lee R-S , Gau J-T
Published: April 2010

Owing to the extensive applications of stainless steel 304 on a microscale, a series of microscale tensile and dome height tests were conducted to investigate its size effects on mechanical properties and formability. Based on the experimental results and observations and the Oh et al. fracture criterion, two new models were proposed in this paper for predicting the forming limit of stainless steel 304 foils in microscale sheet metal forming. For the mechanical properties study, foils of four thicknesses (150 μm, 100 μm, 50 μm, and 20 μm) heat treated at four temperatures (900 °C, 950 °C, 1000 °C, and 1050 °C) were used for the experiments. For the formability prediction, the first proposed model includes the effect of the strain path while the second proposed model considers the coupling effects of both the strain path and the size effects. The first model is superior to the Oh et al. criterion with respect to predicting the forming-limit strain of the foils, but it is not suitable for foils that are thinner than 100 μm. However, the second proposed model can be used for stainless steel 304 foils irrespective of their thicknesses and thickness-to-average-grain-size ratios T/ D. It can also be concluded that the size effects must be considered in microformability when the foil thickness is smaller than 100 μm.
Using the Single Reciprocal Screw to Confirm Mobility of a Six-Revolute Linkage
Authors: Baker J E
Published: April 2010

Overconstrained kinematic chains have been discovered mostly by analytical or geometrical means or through a synthesizing procedure. In a few instances they have succumbed to computer-aided methods, and those solutions can, in effect, be reduced to a single one. This loop, of six revolutes, is described by parametric conditions that provide little information about its physical make-up. The existence of a lone screw reciprocal to the system defined by the loop's joint screws is the basis here for demonstrating analytically the linkage's mobility and determining its mode of assembly. In addition, it is shown that seven new linkages can be developed from this solution as isomeric variants.
Incipient Slip Conditions in the Rolling Contact of Tyred Wheels
Authors: Reina S , Hills D A , Dini D
Published: April 2010

The contact problem of a driving tyred wheel, pressed and rolling over an elastically similar half-plane, is considered. Although applicable to a wide range of shrink-fitted assemblies, the simplified model is solved to study the practical case of an elastically similar steel tyre mounted on a locomotive steel wheel subjected to tractive rolling. The behaviour of the system at the tyre—substrate interface is studied using closed-form solutions to calculate the state of stress within the tyre. Conditions leading to incipient slip and/or plasticity are identified and mapped for different loads and geometries.
A Mixed and Multi-Step Higher-Order Implicit Time Integration Family
Authors: Rezaiee-Pajand M , Sarafrazi S R
Published: April 2010

This article develops a new time integration family for second-order dynamic equations. A combination of the trapezoidal rule and higher-order Newton backward extrapolation functions are utilized in the formulation. Five members of the suggested family are extensively studied in this article. Most members of the presented time integration family are new. The stability and accuracy of the proposed time integration schemes are investigated by solving some benchmark problems. Numerical results are checked and compared with well-known strategies. The findings of the article show the efficiency, accuracy and robustness of the suggested techniques.
An indentation depth—force sensing wheeled probe for abnormality identification during minimally invasive surgery
Authors: Liu H , Puangmali P , Zbyszewski D , Elhage O , Dasgupta P , Dai J S , Seneviratne L , Althoefer K
Published: April 2010

This paper presents a novel wheeled probe for the purpose of aiding a surgeon in soft tissue abnormality identification during minimally invasive surgery (MIS), compensating the loss of haptic feedback commonly associated with MIS. Initially, a prototype for validating the concept was developed. The wheeled probe consists of an indentation depth sensor employing an optic fibre sensing scheme and a force/torque sensor. The two sensors work in unison, allowing the wheeled probe to measure the tool—tissue interaction force and the rolling indentation depth concurrently. The indentation depth sensor was developed and initially tested on a homogenous silicone phantom representing a good model for a soft tissue organ; the results show that the sensor can accurately measure the indentation depths occurring while performing rolling indentation, and has good repeatability. To validate the ability of the wheeled probe to identify abnormalities located in the tissue, the device was tested on a silicone phantom containing embedded hard nodules. The experimental data demonstrate that recording the tissue reaction force as well as rolling indentation depth signals during rolling indentation, the wheeled probe can rapidly identify the distribution of tissue stiffness and cause the embedded hard nodules to be accurately located.
An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression
Authors: Barlow Nicola L , Holme Jayne , Stockley Robert A , Clark Penelope M
Published: April 2010

Background

Since more than 90% of cortisol is bound to protein, serum free cortisol (SFC) may be a more appropriate marker of adrenal status than total cortisol. However, measurement of SFC is technically difficult and calculated SFC may offer a more practical alternative.

Methods

SFC, measured by equilibrium dialysis coupled with immunoassay, and calculated using Coolens' equation from total cortisol and corticosteroid binding globulin (CBG) concentrations, was compared in short Synacthen test (SST) serum from 42 patients, of whom 20 demonstrated a suppressed adrenal response.

Results

Considering the patient group as a whole, calculated SFC was found to be significantly lower than measured SFC, pre- and post-Synacthen ( P < 0.05 and <0.001, respectively). Upon classifying the patients as pass or fail based on total cortisol response to Synacthen, the difference in calculated and measured SFC only reached statistical significance for post-Synacthen concentrations in the pass group ( P < 0.01), suggesting a greater discrepancy at higher cortisol concentrations. There was no difference in CBG levels between the pass and fail groups and both measured and calculated SFC gave a diminished 30 min response in subjects deemed to have failed the SST.

Conclusion

Coolens' equation was found to underestimate measured SFC in this cohort of outpatients, as has been previously demonstrated, particularly in patients with a pronounced acute phase response. Although calculated SFC gave a diminished response in individuals deemed to have failed the SST, the concentration-dependent nature of the discrepancy may limit the usefulness of this method for assessing adrenal status.
Allied health professionals' intention to work for the National Health Service: a study of stayers, leavers and returners
Authors: Coombs Crispin , Arnold John , Loan-Clarke John , Bosley Sara , Martin Caroline
Published: April 2010

While there has been a recent squeeze on staff costs, it continues to be important to offer graduating clinical staff National Health Service (NHS) employment in order to maintain the long-term strength of the service. In addition, the experiences of the Canadian nursing profession suggest that complacency about an improving recruitment situation can lead to problems. Consequently, the objective of this study was to identify what influences allied health professionals' (AHPs) intention to work for the NHS. A postal survey was sent to members of four Allied Health Professions equally ( N = 4800), targeting Stayers in, Leavers from, and Returners to, the NHS. One thousand nine hundred and thirty-nine questionnaires were returned giving an overall response rate of 40%. Stayers' intention to remain in the NHS was influenced by continuing professional development opportunities, confidence that they can find NHS work, commitment to their profession, a sense of moral obligation and a belief that other people important to them think it is a good idea. Returners' intention is influenced by similar factors as Stayers. Leavers are influenced by similar factors as Stayers/Returners but to a lesser extent. The study shows that perceptions of various NHS work characteristics, which lead to reasonably positive attitudes towards the NHS, do not necessarily translate into intention to work for it. The study also shows that intention to work for the NHS is not solely dependent on perceptions of NHS jobs and that career-decision-making is a social process, with the opinions of people who are important to AHPs also influencing career decisions.
Ten reasons to be happy about hormone replacement therapy: a guide for patients
Authors: Studd John
Published: April 2010

In spite of the negative press reports following the 2002 Women's Health Initiative (WHI) publication, women can be reassured that in the correct circumstances, hormone replacement therapy (HRT) is beneficial and safe, particularly if treatment is started below the age of 60. Transdermal estradiol is probably safer than oral estrogens as coagulation factors are not induced in the liver and HRT is safer if a minimal duration and dose of progestogen is used. HRT is effective for the treatment of estrogen-deficiency symptoms of flushes, sweats and vaginal dryness. Estrogens prevent osteoporotic fractures and should be first-choice therapy, rather than bisphosphonates. Similarly, HRT protects the intervertebral discs in a way that non-hormonal preparations do not. Estrogens perhaps with the addition of testosterone help certain sorts of reproductive depression, as well as improving energy and libido. There is new evidence to support the previous observational studies that HRT reduces the incidence of heart attacks. Estrogen therapy has a beneficial effect upon collagen, thus improving the texture of the skin, the nails, the intervertebral discs and bone matrix. Discussion of side-effects should not be avoided, particularly the 1% extra lifetime risk of breast cancer. This should be balanced against the fewer heart attacks, fewer deaths and less osteoporotic fractures in those who start HRT below the age of 60.
Anthropometric and gynaecological history according to the socioeconomic status of postmenopausal women: poverty and the menopause
Authors: Navarro Manuel Carmen , Sosa Manuel , Saavedra Pedro , Gil-Antullano Santiago Palacios , Castro Rosa , Bonet Mario , Travesí Isabel , de Miguel Emilio
Published: April 2010

Background

Less advantaged social classes usually have unhealthier lifestyles and have more difficult access to health resources. In this work we study the possible association between poverty and the prevalence of obesity and oophorectomy in a population of postmenopausal women.

Design

Cross-sectional observational study.

Objective

To study in a population of postmenopausal women in poverty the possible differences in the prevalence of obesity and oophorectomy, and to compare some other gynaecological data: age at menarche, age at menopause, fertile years, number of pregnancies, breastfeeding and the use of hormonal replacement therapy (HRT).

Method

All patients were interviewed personally. A questionnaire was used to find out about their lifestyles and the medication they were taking. Their medical records were reviewed to confirm the existence of some diseases. A complete physical examination was performed with every patient. Weight and height were measured with the patient dressed in light clothes. Blood was obtained in a fasting state in order to carry out some analyses. Poverty was defined according to the Spanish National Institute of Statistics criteria.

Results

We enrolled 1225 postmenopausal women; 449 (36.6%) were under the threshold of poverty, defined by the Spanish National Institute of Statistics. Postmenopausal women in poverty had higher body mass index (29.2 ± 4.8 versus 27.0 ± 4.7 kg/m2 P < 0.001), and a higher prevalence of obesity than postmenopausal women not in poverty (44.2% versus 24.3%, P = 0.001). The prevalence of oophorectomy was also higher in women in poverty (32.7% versus 27.2%, P < 0.04). Women in poverty had had a greater number of pregnancies (3 versus 2, P = 0.001). They also showed a higher rate of breastfeeding than women in medium and high social classes (65% versus 59%, P = 0.037). There were no statistically significant differences between the groups in either the age of menopause or fertile years, nor in the use of HRT.

Conclusions

Postmenopausal women in poverty have higher levels of obesity, and also a greater prevalence of oophorectomy than women of medium and high social classes. They also presented a higher rate of breastfeeding and a greater number of pregnancies than those women not in poverty.
Noncanonical transcript forms in yeast and their regulation during environmental stress
Authors: Yoon Oh Kyu , Brem Rachel B.
Published: April 2010

Surveys of transcription in many organisms have observed widespread expression of RNAs with no known function, encoded within and between canonical coding genes. The search to distinguish functional RNAs from transcriptional noise represents one of the great challenges in genomic biology. Here we report a next-generation sequencing technique designed to facilitate the inference of function of uncharacterized transcript forms by improving their coverage in sequencing libraries, in parallel with the detection of canonical mRNAs. We piloted this protocol, which is based on the capture of 3′ ends of polyadenylated RNAs, in budding yeast. Analysis of transcript ends in coding regions uncovered hundreds of alternative-length coding forms, which harbored a unique sequence motif and showed signatures of regulatory function in particular gene categories; independent single-gene measurements confirmed the differential regulation of short coding forms during heat shock. In addition, our 3′-end RNA-seq method applied to wild-type strains detected putative noncoding transcripts previously reported only in RNA surveillance mutants, and many such transcripts showed differential expression in yeast cultures grown under chemical stress. Our results underscore the power of the 3′-end protocol to improve detection of noncanonical transcript forms in a sequencing experiment of standard depth, and our findings strongly suggest that many unannotated, polyadenylated RNAs may have as yet uncharacterized regulatory functions.
Everyday Memory and Working Memory in Adolescents With Mild Intellectual Disability
Authors: Van der Molen M. J. , Van Luit J. E. H. , Van der Molen Maurits W. , Jongmans Marian J.
Published: April 2010

Everyday memory and its relationship to working memory was investigated in adolescents with mild intellectual disability and compared to typically developing adolescents of the same age (CA) and younger children matched on mental age (MA). Results showed a delay on almost all memory measures for the adolescents with mild intellectual disability compared to the CA control adolescents. Compared to the MA control children, the adolescents with mild intellectual disability performed less well on a general everyday memory index. Only some significant associations were found between everyday memory and working memory for the mild intellectual disability group. These findings were interpreted to suggest that adolescents with mild intellectual disability have difficulty in making optimal use of their working memory when new or complex situations tax their abilities.
Pathways Through Services for Offenders With Intellectual Disability: A One- and Two-Year Follow-Up Study
Authors: Lindsay William R. , Holland Tony , Wheeler Jessica R. , Carson Derek , O'Brien Gregory , Taylor John L. , Steptoe Lesley , Middleton Claire , Price Karen , Johnston Susan , Young Steven J.
Published: April 2010

The pathways through services for offenders with intellectual disability were reviewed. Participants were 197 offenders with intellectual disability accepted into three types of community and three types of secure forensic intellectual disability services. They were first compared with 280 participants referred but not accepted into services and were then followed-up for 2 years to review pathways through services. Those accepted into services had a higher charge rate than did those who were referred (46% and 25%, respectively). The greatest diversity in pathway was seen in participants in community forensic intellectual disability and inpatient services. Individuals in secure settings showed the least diversity over time, and, similarly, a relatively high percentage of those accepted into generic community services remained in these services.
Fatigue from an Induced Defect: Experiments and Application of Different Multiaxial Fatigue Approaches
Authors: Leopold Gaëlle , Nadot Yves
Published: April 2010

An experimental database containing multiaxial fatigue results for C35 steel with induced defects has been previously published [Billaudeau, T., Nadot, Y., and Bezine, G., “Multiaxial Fatigue Limit for Defective Materials: Mechanisms and Experiments,” Acta Mater., Vol. 52, 2004, pp. 3911–3920; Nadot, Y., and Billaudeau, T., “Multiaxial Fatigue Limit Criterion for Defective Materials,” Eng. Fract. Mech., Vol. 73, 2006, pp. 112–133; Gadouini, H., Nadot, Y., and Rebours, C., “Influence of Mean Stress on the Multiaxial Fatigue Behaviour of Defective Materials,” Int. J. Fatigue, Vol. 30, 2008, pp. 1623–1633]. Artificial defects, in a range of 100–900 μm, are introduced at the surface of fatigue samples. The database contains experimental fatigue results for different defect size and geometry, and multiaxial loading cases with different load ratios. In the present study, five models predicting the fatigue limit of materials with defects are compared. Each model is carefully presented, predictions are compared, and input data are discussed. It is shown that it is necessary to take account for the stress distribution around the defect in order to have a good prediction for a multiaxial case.
Measurement of Mechanical Properties of Hydrated Cement Paste Using Resonant Ultrasound Spectroscopy
Authors: Wu W. , Al-Ostaz A. , Gladden J. , Cheng A. H.-D. , Li G.
Published: April 2010

The resonant ultrasound spectroscopy (RUS) experimental technique had been used successfully to measure the modulus of elasticity and Poisson’s ratio of hydrated cement paste. RUS is a modern nondestructive acoustic technique, which can be applied to determine the elastic properties of solids with high precision and great efficiency. By measuring the natural resonance frequencies for a single small parallelepiped cement paste sample with water cement ratio of 0.4, the elastic constants and, subsequently, the modulus (E) and Poisson’s ratio (v) were obtained. The results from RUS measurement, E=21.55 GPa and v=0.225, agree with the numerical modeling values.
The GH-2004 project: the response of IGF1 and type III pro-collagen to the administration of exogenous GH in non-Caucasian amateur athletes
Authors: Holt Richard I G , Erotokritou-Mulligan Ioulietta , McHugh Cathy , Bassett E Eryl , Bartlett Christiaan , Fityan Adam , Bacon Jenny L , Cowan David A , Sönksen Peter H
Published: April 2010

Context

The GH-2000 team proposed a method based on IGF1 and type III pro-collagen (P-III-P) to detect exogenously administered GH. As previous studies involved predominantly white European athletes, it is important to assess whether the response of these markers to recombinant human GH (rhGH) differs with ethnicity.

Objective

To examine the response of serum IGF1 and P-III-P and GH-2000 score to rhGH in non-Caucasian amateur athletes.

Design

Double-blind placebo-controlled rhGH administration study.

Setting

Wellcome Trust Clinical Research Facility, Southampton General Hospital.

Subjects

The study included 31 male and 14 female amateur athletes of different ethnicities.

Intervention

The subjects were assigned to treatment with placebo or 0.1 IU/kg per day (low dose) or 0.2 IU/kg per day (high dose) rhGH for 28 days. Blood was collected weekly during treatment and on days 35, 42 and 84 during the washout period. Serum IGF1 and P-III-P were measured, and GH-2000 score was calculated.

Results

IGF1, P-III-P and GH-2000 score rose in response to both low- and high-dose GH in both men and women. When compared with the Caucasian volunteers of the previous GH-2000 study, mean baseline and placebo-treated P-III-P and GH-2000 score were lower in GH-2004 men and women. Post-GH, however, peak IGF1 or P-III-P did not differ between studies but the peak GH-2000 score was lower in GH-2004 men. There was no difference between studies in the maximal change in IGF1, P-III-P and GH-2000 score in response to GH in either gender.

Conclusions

These data do not support a significant ethnic effect on the peak or maximal response to rhGH.