bluuebunny/crossref_metadata_2025 huggingface dataset:
Type I Glanzmann thrombasthenia caused by an apparently silent β3 mutation that results in aberrant splicing and reduced β3 mRNA
Authors: Xie Jingli , Pabón Dina , Jayo Asier , Butta Nora , González-Manchón Consuelo
Published: April 2005

We report a novel genetic defect in a patient with type I Glanzmann thrombasthenia. Flow cytometry analysis revealed undetectable levels of platelet glycoproteins αIIb and β3, although residual amounts of both proteins were detectable in immunoblotting analysis. Sequence analysis of reversely transcribed platelet β3 mRNA showed a 100-base pair deletion in the 3’-boundary of exon 11, that results in a frame shift and appearance of a premature STOP codon. Analysis of the corresponding genomic DNA fragment revealed the presence of a homozygous C1815T transition in exon 11. The mutation does not change the amino acid residue but it creates an ectopic consensus splice donor site that is used preferentially, causing splicing out of part of exon 11. The parents of the proband, heterozygous for this mutation, were asymptomatic and had reduced platelet content of αIIbβ3. PCR-based relative quantification of β3 mRNA failed to detect the mutant transcript in the parents and showed a marked reduction in the patient. The results suggest that the thrombasthenic phenotype is, mainly, the result of the reduced availability of β3-mRNA, most probably due to activation of the nonsense-mediated mRNA decay mechanism. They also show the convenience of analyzing both genomic DNA and mRNA, in order to ascertain the functional consequences of single nucleotide substitutions.
Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries
Authors: Cazanave Alain , Elias Marie , Chabbert Valérie , Juchet Henri , Paradis Hélène , Carrière Philippe , Nguyen Françoise , Didier Alain , Galinier Michel , Colin Cyrille , Lauque Dominique , Joffre Francis , Rousseau Hervé , Elias Antoine
Published: April 2005

The objective of the study was to assess the clinical validity of a non-invasive diagnostic strategy for acute pulmonary embolism using clinical assessment combined with both ELISA D-dimer and complete lower limb ultrasound (US) examination of proximal and distal veins, before single-detector helical computed tomography (CT) of pulmonary arteries. We expected the strategy to have a high diagnostic exclusion power and to safely decrease the number of CT scans. This prospective, multicenter outcome study included 274 consecutive outpatients. All underwent a priori clinical probability, D-dimer and bilateral complete lower limb US assessments. Only patients with a high clinical probability and both tests negative, or positive D-dimer and negative US assessments, underwent CT. This was deemed necessary in 114 patients (42%). At baseline, venous thromboembolism (VTE) was detected in 110 patients (40%), either by US showing proximal (n=65) or distal (n=36) thrombosis, or by CT (n=9). Anticoagulant was withheld in the remaining patients with negative results in both D-dimer and US but a non-high clinical probability (n=59), or in both US and CT (n=90), or with negative US (n=6) and inadequate CT (n=9). All patients underwent a three-month clinical follow-up. VTE occurred in one patient with inadequate CT, yielding an incidence of 0.6% [95% confidence interval: 0.1–3.4]. No patient died from VTE or had major bleeding. Using clinical probability, ELISA D-dimer and complete US before helical CT is a safe strategy resulting in a substantial reduction in CT scans.
Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation
Authors: Sconce Elizabeth , Khan Tayyaba , Mason Jennifer , Noble Faye , Wynne Hilary , Kamali Farhad
Published: April 2005

Evidence suggests that alterations in the dietary intake of vitamin K can affect anticoagulation response to warfarin. It is possible that a low and erratic intake of dietary vitamin K is at least partly responsible for the variable response to warfarin in patients with unstable control of anticoagulation. Twenty-six patients with unstable and twenty-six with stable control of anticoagulation completed dietary records of all foods and drinks consumed on a daily basis for two consecutive weeks. The mean daily intake of vitamin K in unstable patients was considerably lower than that for stable patients during the study period (29±17μg v. 76±40µg). The logarithm of vitamin K intake was consistently and significantly lower in the unstable patients than the stable patients over the two week period (5.9±0.4µg v. 6.9±0.5µg; p<0.001; 95% CI: 0.7–1.2). Changes in vitamin K intake between weeks 1 and 2 of the study were negatively correlated with changes in International Normalised Ratio (INR) amongst the unstable patients, however this failed to reach significance (r=-0.25; p=0.22). Daily supplementation with oral vitamin K in unstable patients could lead to a more stable anticoagulation response to warfarin.
A Statistical Method for Correcting Salinity Observations from Autonomous Profiling Floats: An ARGO Perspective
Authors: Durand Fabien , Reverdin Gilles
Published: April 2005

The Profiling Autonomous Lagrangian Circulation Explorer (PALACE) float is used to implement the Array for Real-Time Geostrophic Oceanography (ARGO). This study presents a statistical approach to correct salinity measurement errors of an ARGO-type fleet of PALACE floats. The focus is on slowly evolving drifts (typically with time scales longer than a few weeks). Considered for this case study is an ensemble of about 80 floats in the Irminger and Labrador Seas, during the 1996–97 period. Two different algorithms were implemented and validated based on float-to-float data comparison at depth, where the water masses are relatively stable over the time scales of interest. The first algorithm is based upon objective analysis of the float data, while the second consists of a least squares adjustment of the data of the various floats. The authors’ method exhibits good skills to retrieve the proper hydrological structure of the case study area. It significantly improves the consistency of the PALACE dataset with in situ data as well as with satellite altimetric data. As such, the method is readily usable on a near-real-time basis, as required by the ARGO project.
Evaluation of the Dropsonde Humidity Sensor Using Data from DYCOMS-II and IHOP_2002
Authors: Wang Junhong
Published: April 2005

The dropsonde humidity data have not been fully utilized due to lack of knowledge on performance of the dropsonde humidity sensor. This study evaluates the performance of the dropsonde humidity sensor using data collected from two field experiments, the Dynamics and Chemistry of Marine Stratocumulus Phase II: Entrainment Studies (DYCOMS-II) and the International H2O Project (IHOP)_2002. During DYCOMS-II, 63 dropsondes were dropped above marine stratocumulus clouds. It provides a unique opportunity to evaluate the performance of the dropsonde humidity sensor within clouds. Relative humidity (RH) inside clouds did not reach 100% all the time, but the maximum RH reached 100% for 28% of soundings and was within the sensor accuracy range (94%–100%). This suggests that the dropsonde humidity sensor displays no systematic dry bias near saturation. The dropsonde humidity sensor experienced large time-lag errors when it descended from a dry environment above clouds into clouds. The mean estimated time constant of the sensor is 5 s at 15°C, which is much larger than 0.5 s at 20°C given by the manufacturer. The humidity sensor still reported near-saturation RH after it exited clouds because of water on the sensor. The approximately coincident dropsonde and aircraft temperature data during DYCOMS-II show that the dropsonde underestimates temperatures inside and below clouds by averages of 0.21° and 0.93°C, respectively. Seventy-one pairs of dropsonde and radiosonde soundings during IHOP_2002 were launched within a half hour and 50 km and sampled the same air mass based on the visual examination. The comparisons show that the dropsonde and radiosonde RH data agree with each other within ±2% RH, suggesting no systematic dry bias in dropsonde humidity data. However, dropsonde-measured temperature is consistently colder than that by radiosonde by ∼0.4°C.
Directionality and Crest Length Statistics of Steep Waves in Open Ocean Waters
Authors: Scott Nicholas , Hara Tetsu , Hwang Paul A. , Walsh Edward J.
Published: April 2005

A new wavelet analysis methodology is applied to open ocean wave height data from the Southern Ocean Waves Experiment (1992) and from a field experiment conducted at Duck, North Carolina, in 1997 with the aim of estimating the directionality and crest lengths of steep waves. The crest directionality statistic shows that most of the steep wave crests are normal to the direction of the mean wind. This is inconsistent with the Fourier wavenumber spectrum that shows a broad bimodal directional spreading at high wavenumbers. The crest length statistics demonstrate that the wave field is dominated by short-crested waves with small crest length/wavelength ratios. The one-dimensional steep wave statistic obtained from the integration of the directional (two dimensional) steep wave statistic is consistent with the one-dimensional steep wave statistic obtained from the one-dimensional analysis at high wave slope thresholds.
Gas metal arc welding of butt joint with varying gap width based on neural networks
Authors: Christensen K.H. , Sørensen T. , Kristensen J.K.
Published: April 2005

Arc welding is still the dominant welding process in industry and a major challenge in this context is robotisation and automation, which require sensor based adaptive control. Therefore, the present paper describes the application of neural network technology for gas metal arc welding control. A system based on a multilayer feed forward network has been developed for modelling and online adjustment of welding parameters appropriate to guarantee a certain degree of quality in the field of butt joint welding with full penetration when the gap varies during the welding process. It has been shown that operating in an open loop, the developed system can tackle gap variations relevant to many welding situations. However, to improve robustness to uncertainties, disturbances, etc. a closed loop control system based on a ‘single neuron self-learning proportional, sum, and differential’ control algorithm, which compensates for non-monitorial changes in welding conditions by feeding back information on the realised front bead geometry, has also been developed and tested. The Levenberg–Marquardt algorithm for non-linear least squares has been used with a back propagation algorithm for training the neural networks, and a Bayesian regularisation technique has been successfully applied for minimising the risk of inexpedient overtraining.
Seam tracking based on estimation of weld position using Kalman filtering
Authors: Xiangdong Gao , Na S.-J.
Published: April 2005

A seam tracking method is presented based on the estimation of weld position during the gas tungsten arc welding process. Kalman filtering of the weld pool images from a visual sensor is applied to compute recursively the solution to the weld position equations which are established based on an estimation of the centroid position of the weld pool images. This centroid, the position of which corresponds with the weld position, is extracted as the measurement eigenvector. The evolution of the weld position data from the weld pool images can be described through an appropriate process model, so that the weld position can be detected by applying a Kalman filter. This allows adjustment of the welding torch position in real time, which may significantly reduce processing time and promote seam tracking accuracy. Simulations and actual welding experiments have demonstrated the effectiveness of the proposed algorithm in the presence of weld pool image noise and have demonstrated the robustness of weld position detection for seam tracking.
Feed forward control of back bead and bead height in narrow gap robotic welding
Authors: Yamane S. , Sharif L.H. , Zeniya S. , Oshima K.
Published: April 2005

For high quality welding, it is necessary to form a stable back bead and to melt metal plates. In narrow gap welding, it is difficult to control the bead height and the back bead simultaneously using conventional welding. In order to solve this problem, a switch back welding method is proposed in which the welding torch is moved back and forth along the welding line. In the forward movement of the torch, the arc heat is given to the root edges to obtain a wide back bead. In the backward movement, suitable bead height is formed. From the fundamental experimental results, a numerical model was prepared for this type of welding. Using this model, the optimum stroke length was found. Its validity was verified by carrying out welding experiments.
Repair welding of cracked turbine shroud using matching composition consumables
Authors: Das C.R. , Ramasubbu V. , Bhaduri A.K. , Ray S.K.
Published: April 2005

Repair welding of a crack in the III-stage shroud of a high pressure turbine, was carried out using matching composition ER 410 filler wire by the gas tungsten arc welding (GTAW) process with ultra high purity argon as shielding and backing gas. The development of the repair welding procedure involved laboratory studies for the selection of a suitable ER410 filler wire, optimisation of welding parameters and PWHT. Mock up welding under simulated on-site constraints confirmed the feasibility to produce in situ sound weld joint. In situ repair welding and localised PWHT was carried out successfully. NDT and in situ metallography of the repair-welded region confirmed adequate tempering of the martensitic weldment during the localised PWHT.
Residual stresses in spot welded new generation aluminium alloys Part B – finite element simulation of residual stresses in a spot weld in 5754 aluminium alloy
Authors: Long X. , Khanna Sanjeev K.
Published: April 2005

An incremental thermo-electrical-mechanical coupled finite element model has been developed for predicting the residual stress field in a 5754 aluminium alloy spot welded joint. The complete spot welding process, including squeezing, welding, holding and cooling cycles, as well as the temperature and stress histories during those cycles in the welded joint have been investigated. All the required thermo-physical and thermo-mechanical properties used were experimentally measured. The results show that tensile residual stress predominates the spot nugget area. The highest tensile residual stress, with a value close to the material's yield strength, occurs around the centre of the nugget. The residual stress value decreases slightly towards the edge of the spot nugget.
Coupled arc and droplet model of GMAW
Authors: Quinn T.P. , Szanto M. , Gilad I. , Shai I.
Published: April 2005

A model of gas metal arc welding was developed that solves the magnetohydrodynamic equations for the flow and temperature fields of the molten electrode and plasma simultaneously, to form a fully coupled model. A commercial finite-element code was extended to include the effects of radiation, Lorentz forces, Joule heating and thermo-electric effects. The model predicts the shape of the free surfaces of the molten metal as the droplets form, detach, and merge with the weld pool. It also predicts the flow, temperature, and electric field. Material properties and the welding parameters are the input variables in the model. The geometry of the numerical model was constructed to fit an experimental apparatus using an aluminium electrode and an argon shielding gas. Droplet frequency measurements were used to verify the model's predictions. For a typical arc, the temperature of the plasma can range up to 20 000 K, where there is more uncertainty in the thermophysical properties of the plasma, and the properties in this range are highly non-linear. For this range, the material properties of the model were adjusted to obtain a better fit between the numerical and the experimental results. The model and experimental results were comparable.
Short fatigue crack growth behaviour of a ferritic steel weld metal
Authors: Venkateswaran P. , Ganesh Sundara Raman S. , Pathak S.D.
Published: April 2005

The present study deals with the short fatigue crack growth behaviour of a ferritic steel (nuclear grade SA 333 Grade 6 steel) weld metal at two load ratios R of 0.1 and –1. Single edge notched weld joint specimens were tested at different stress levels. The acceleration and deceleration in short crack growth with increasing stress intensity factor range was explained in terms of microstructure of weld metal. Acicular ferrite and grain boundary ferrite acted as barriers to crack growth. Non-propagating cracks were observed due to multiple cracks and blocking by ferrite grain boundaries. Transition crack length, the limiting crack length above which the crack exhibited a typical long crack behaviour, was determined to be 1 mm at R=0.1 and 1.5 mm at R=2 1.
Laser induced stabilisation of the welding arc
Authors: Hu B. , den Ouden G.
Published: April 2005

This paper deals with the influence of laser radiation on the stability of the welding arc. Experiments were conducted using a low power (500 W) Nd:YAG laser in combination with a gas tungsten welding arc. The laser induced arc stabilising effect was measured under various experimental conditions. It was found that the stabilising effect can be explained in terms of two phenomena: the absorption of laser energy by the arc plasma and the change of the arc plasma composition caused by strong evaporation of workpiece material. Both phenomena lead to a reduction of the effective ionisation potential of the plasma and thus provide a more conductive, stable plasma channel for arc root and column that overcomes disturbance by external forces. The proposed stabilisation mechanism was validated by measuring the absorption of laser energy by the arc plasma using a laser energy meter and the changes of arc plasma composition caused by the laser radiation by means of emission spectroscopy.
Ly49 and CD94/NKG2 receptor acquisition by NK cells does not require lymphotoxin-β receptor expression
Authors: Stevenaert Frederik , Van Beneden Katrien , De Colvenaer Veerle , Franki Ann Sophie , Debacker Veronique , Boterberg Tom , Deforce Dieter , Pfeffer Klaus , Plum Jean , Elewaut Dirk , Leclercq Georges
Published: April 2005

A crucial step in murine natural killer (NK) cell development, mediated by bone marrow stromal cells, is the induction of Ly49 and CD94/NKG2 receptor expression. The signals that regulate Ly49 receptor expression are still largely undetermined. It has been shown that interaction between lymphotoxin α1β2 (LTα1β2) and LTβ receptor (LTβR), expressed on lymphoid progenitor cells and nonlymphoid bone marrow stromal cells, respectively, is important for both quantitative and functional NK cell development. Therefore, we have investigated the role of LT-LTβR–mediated signaling in Ly49 and CD94/NKG2 receptor acquisition. We show that the NK receptor repertoire of LTβR–/– mice can only be partially analyzed because of the residual 129/Ola mouse genetic background, due to a physical linkage of the LTβR locus and the loci encoding the Ly49 and CD94/NKG2 receptors. Therefore, we transferred wild-type B6 lymphoid-committed progenitor cells into LTβR–/– mice, which differentiated into NK cells with a normal NK cell receptor repertoire. Also, administration of LTβR-immunoglobulin (Ig), which acts as a soluble receptor for LTα1β2, resulted in reduced NK cell percentages but did not influence the Ly49 and CD94/NKG2 receptor acquisition on remaining NK cells. These results indicate that LTβR-mediated signals are not required for Ly49 and CD94/NKG2 receptor acquisition.
Regional induction of adhesion molecules and chemokine receptors explains disparate homing of human B cells to systemic and mucosal effector sites: dispersion from tonsils
Authors: Johansen Finn-Eirik , Baekkevold Espen S. , Carlsen Hege S. , Farstad Inger Nina , Soler Dulce , Brandtzaeg Per
Published: April 2005

Ethical constraints restrict direct tracking of immune-cell migration throughout the human body in vivo. We, therefore, used deletion of the immunoglobulin M (IgM) heavy-chain constant-gene (Cμ) segment as a marker to provide a dispersal signature of an effector B-cell subset (IgD+IgM-CD38+) induced selectively in human tonsils. By DNA analysis, the Cμ deletion identified dissemination of such blasts and their plasma-cell progeny to peripheral blood, lymph nodes, and bone marrow, as well as to mucosae and glands of the upper airways. Also the endocervix was often positive, while the small intestine was mainly negative, as could be expected from the identified homing-molecule profile of the marker cells, with relatively low levels of integrin α4β7 and CC chemokine receptor 9 (CCR9). Of further importance for vaccine design, the circulating cells expressed abundantly CD62L (L-selectin) and CCR7, which provided a mechanism for integration of respiratory and systemic immunity. Most mucosal vaccines are at present administered perorally, and our results suggested that the nasal route is no alternative for vaccination against rotavirus or other small-intestinal infections in humans. However, immunization of nasopharynx-associated lymphoid tissue clearly appears preferable to target respiratory pathogens and may to some extent also protect against infections of the female genital tract. (Blood. 2005;106:593-600)
Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma
Authors: Raje Noopur , Kumar Shaji , Hideshima Teru , Roccaro Aldo , Ishitsuka Kenji , Yasui Hiroshi , Shiraishi Norihiko , Chauhan Dharminder , Munshi Nikhil C. , Green Simon R. , Anderson Kenneth C.
Published: April 2005

Cyclin-dependent kinase (CDK) inhibitors have the potential to induce cell-cycle arrest and apoptosis in cancer cells. Seliciclib (CYC202 or R-roscovitine) is a potent CDK inhibitor currently undergoing phase-2 clinical testing in lung and B-cell malignancies. Here we studied the in vitro cytotoxic activity of seliciclib against multiple myeloma (MM) cells. Our data demonstrate that seliciclib has potent cytotoxicity against MM cells that are both sensitive and resistant to conventional therapy as well as primary MM cells from patients. Cell-cycle and Western blot analysis confirmed apoptosis. Importantly, seliciclib triggered a rapid down-regulation of Mcl-1 transcription and protein expression independent of caspase cleavage. Adherence of MM cells to bone marrow stromal cells (BMSCs) induced increased Mcl-1 expression associated with signal transducer and activator of transcription 3 (STAT3) phosphorylation, which was inhibited in a time- and dose-dependent manner by seliciclib. Furthermore, seliciclib inhibited interleukin 6 (IL-6) transcription and secretion triggered by tumor cell binding to BMSCs. Up-regulation of Mcl-1 expression in cocultures was only partially blocked by neutralizing antibody to IL-6, suggesting alternative mechanisms of Mcl-1 modulation by seliciclib. Finally, combination studies of seliciclib with doxorubicin and bortezomib show in vitro synergism, providing the rationale for testing these drug combinations to improve patient outcome in MM.
Proliferation dynamics of germinative zone cells in the intact and excitotoxically lesioned postnatal rat brain
Authors: Faiz Maryam , Acarin Laia , Castellano Bernardo , Gonzalez Berta
Published: April 2005

Background

The forebrain subventricular zone (SVZ)-olfactory bulb pathway and hippocampal subgranular zone (SGZ) generate neurons into adulthood in the mammalian brain. Neurogenesis increases after injury to the adult brain, but few studies examine the effect of injury on neural and glial precursors in the postnatal brain. To characterize the spatio-temporal dynamics of cell proliferation in the germinative zones, this study utilized a model of postnatal damage induced by NMDA injection in the right sensorimotor cortex at postnatal day 9.

Dividing cell populations were labeled with 5-Bromodeoxyuridine (BrdU) in the intact and damaged postnatal brain. Identity of proliferating cells was determined by double immunolabeling with nestin, GFAP, NeuN and tomato lectin (TL).

Results

In the control brain, grouped BrdU+ cells were observed in the Rostral Migratory Stream (RMS), SVZ and SGZ. Maximal proliferation was seen at P12, persisted until P23 and diminished by P49. After injury, a striking reduction in the number of BrdU+ cells was observed in the ipsilateral SVZ from 10 hours (58% decrease) until 14 days post-lesion (88% decrease). In contrast, an increase in grouped BrdU+ cells was seen in the striatum adjacent to the depleted SVZ. Significantly reduced numbers of BrdU+ cells were also seen in the RMS until 3 days post-lesion. No changes were noted in the SGZ. Both in controls and lesioned hemispheres, BrdU+ cells located in the germinal zones were mostly nestin positive and negative for GFAP, NeuN, and TL. In the SVZ area lining the ventricle, BrdU+/nestin+ cells were mainly located between TL+ ependyma and parenchymal GFAP+ astrocytes. After excitotoxicity, a decrease in the number and orientation of GFAP/nestin+ prolongations leaving the SVZ to the cortex, corpus callosum and striatum was noted until 5 days post-lesion.

Conclusion

Postnatal excitotoxic injury differentially affects proliferating cells in the germinative zones: no change is observed in the dentate gyrus whereas excitotoxicity causes a significant decrease in proliferating cells in the SVZ and RMS. Depletion of BrdU+ cells in the postnatal SVZ and RMS differs from previous studies after adult brain injury and may affect the SVZ-RMS migration and is suggestive of progenitor recruitment to injured areas.
Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells
Authors: Thiele Geoffrey M , Hill Gary E , Pavlik Jacqueline A , Freeman Thomas L , Tuma Dean J , Duryee Michael J , Klassen Lynell W
Published: April 2005

Background

The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization. Halothane is an anesthetic that can be metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which reacts with endogenous proteins to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct which is formed by acetaldehyde (AA) and malondialdehyde reacting with endogenous proteins, has been found in both patients and animals chronically consuming alcohol. These TFA and MAA-adducts have been shown to cause the release of inflammatory products by various cell types. If both adducts share a similar mechanism of cell activation, receiving halothane anesthesia while intoxicated with alcohol could exacerbate the inflammatory response and lead to cardiovascular injury.

Methods

We have recently demonstrated that the MAA-adduct induces tumor necrosis factor-α (TNF-α) release by heart endothelial cells (HECs). In this study, pair and alcohol-fed rats were randomized to receive halothane pretreatments intra peritoneal. Following the pretreatments, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb), MAA-modified Alb (MAA-Alb), Hexyl-MAA, or lipopolysaccharide (LPS), and supernatant concentrations of TNF-α were measured by ELISA.

Results

Halothane pre-treated rat HECs released significantly greater TNF-α concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed rats.

Conclusion

These results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-α release). Also, these results suggest that halothane exposure may increase the risk of alcohol-induced heart injury, since halothane pre-treatment potentiates the HEC TNF-α release measured following both MAA-Alb and LPS stimulation.
Who wants to join preventive trials? – Experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]
Authors: Hovi Sirpa-Liisa , Hakama Matti , Veerus Piret , Rahu Mati , Hemminki Elina
Published: April 2005

Background

The interest of patients in participating in randomized clinical trials involving treatments has been widely studied, but there has been much less research on interest in preventive trials. The objective of this study was to find out how many women would be interested in a trial involving postmenopausal hormone therapy (PHT) and how the women's background characteristics and opinions correlated to their interest.

Methods

The data come from recruitment questionnaires (n = 2000) sent to women in Estonia in 1998. A random sample of women aged 45 to 64 was drawn from the Population Registry. The trial is a two-group randomized trial comparing estrogen-progestogen therapy with placebo or no drugs. A brief description of the study was attached to the questionnaires. Women were not told at this stage of the recruitment which group they would be assigned to, however, they were told of the chance to receive either hormone, placebo or no treatment.

Results

After two reminders, 1312 women (66%) responded. Eleven percent of the women approached (17% of the respondents) were interested in joining the trial, and 8% wanted more information before deciding. When the 225 women who stated clearly that they were interested in joining and the 553 women who said they were not interested were compared, it was found that interested women were younger and, adjusting for age, that more had given birth; in other respects, the sociodemographic characteristics and health habits of the interested women were similar to those of the non-interested women. The interested women had made more use of more health services, calcium preparations and PHT, they were more often overweight, and more had chronic diseases and reported symptoms. Interested women's opinions on the menopause were more negative, and they favoured PHT more than the non-interested women.

Conclusion

Unlike the situation described in previous reports on preventive trials, in this case Estonian women interested in participating in a PHT trial were not healthier than other women. This suggests that trials involving PHT are more similar to treatment trials than to preventive trials. In a randomized controlled trial, more information should be obtained from those women who decline to participate.
Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759]
Authors: Knaebel HP , Märten A , Schmidt J , Hoffmann K , Seiler C , Lindel K , Schmitz-Winnenthal H , Fritz S , Herrmann T , Goldschmidt H , Krempien R , Mansmann U , Debus J , Diehl V , Büchler MW
Published: April 2005

After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation.

Design

The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment.

Discussion

The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.
Why nutraceuticals do not prevent or treat Alzheimer's disease
Authors: Fisher Anna EO , Naughton Declan P
Published: April 2005

A great deal of research has pointed to deleterious roles of metal ions in the development of Alzheimer's disease. These include: i) the precipitation and aggregation of amyloid β (Aβ) peptides to form senile plaques and neurofibrillary tangles, and/or ii) the augmentation of oxidative stress by metal ion mediated production and activation of hydrogen peroxide. The growing trend in nutraceutical intake is in part a result of the belief that they postpone the development of dementias such as Alzheimer's disease. However, pathogenic events centred on metal ions are expected to be aggravated by frequent nutraceutical intake. Novel therapeutic approaches centred on chelators with specificity for copper and iron ions should be fully explored.
Hym-301, a novel peptide, regulates the number of tentacles formed in hydra
Authors: Takahashi Toshio , Hatta Masayuki , Yum Seungshic , Gee Lydia , Ohtani Masahiro , Fujisawa Toshitaka , Bode Hans R.
Published: April 2005

Hym-301 is a peptide that was discovered as part of a project aimed at isolating novel peptides from hydra. We have isolated and characterized the gene Hym-301, which encodes this peptide. In an adult, the gene is expressed in the ectoderm of the tentacle zone and hypostome, but not in the tentacles. It is also expressed in the developing head during bud formation and head regeneration. Treatment of regenerating heads with the peptide resulted in an increase in the number of tentacles formed, while treatment with Hym-301 dsRNA resulted in a reduction of tentacles formed as the head developed during bud formation or head regeneration. The expression patterns plus these manipulations indicate the gene has a role in tentacle formation. Furthermore, treatment of epithelial animals indicates the gene directly affects the epithelial cells that form the tentacles. Raising the head activation gradient, a morphogenetic gradient that controls axial patterning in hydra, throughout the body column results in extending the range of Hym-301 expression down the body column. This indicates the range of expression of the gene appears to be controlled by this gradient. Thus,Hym-301 is involved in axial patterning in hydra, and specifically in the regulation of the number of tentacles formed.
Mechanics of neutrophil phagocytosis: behavior of the cortical tension
Authors: Herant Marc , Heinrich Volkmar , Dembo Micah
Published: April 2005

The mechanical implementation of phagocytosis requires a well-coordinated deployment of cytoplasm and membrane during the creation of a phagosome. We follow the time course of this process in initially round passive neutrophils presented with antibody-coated beads of radii 1.1 to 5.5 μm. In particular, we monitor the cortical tension as the apparent cellular surface area increases due to cell-driven deformations induced by phagocytosis. The behavior of the tension is then compared with conditions of similar area expansion caused by externally imposed deformations during cell aspiration into a micropipette. Whereas the resting tension remains low for an area expansion of up to only 30% during aspiration, it remains low even after an area expansion of up to 80% in phagocytosis. This is probably the result of membrane insertion from inner stores by exocytosis. We further find that the onset of viscous tension, proportional to the rate of area expansion and caused by the unfurling of plasma membrane wrinkles, is significantly delayed in phagocytosis compared with aspiration. We propose that this is the result of phagocytosis-triggered enzymatic activity that releases spare plasma membrane normally sequestered by velcro-like bonds in a reservoir of surface folds and villi.
Non-random chromosome positioning in mammalian sperm nuclei, with migration of the sex chromosomes during late spermatogenesis
Authors: Foster Helen A. , Abeydeera Lalantha R. , Griffin Darren K. , Bridger Joanna M.
Published: April 2005

Chromosomes are highly organized and compartmentalized in cell nuclei. The analysis of their position is a powerful way to monitor genome organization in different cell types and states. Evidence suggests that the organization of the genome could be functionally important for influencing different cellular and developmental processes, particularly at early stages of development (i.e. fertilization and the consequent entry of the sperm nucleus into the egg). The position of chromosomes in the sperm nucleus might be crucial, because their location could determine the time at which particular chromatin domains are decondensed and remodelled, allowing some epigenetic level of control or influence over subsequent paternal gene expression in the embryo. Here, we analyse genome organization by chromosome position in mammalian sperm nuclei from three breeds of pig, as a model species. We have mapped the preferential position of all chromosomes (bar one) in sperm nuclei in two dimensions and have established that the sex chromosomes are the most internally localized chromosomes in mature sperm. The distribution of two autosomes and chromosomes X and Y in sperm heads was compared in primary and secondary spermatocytes and spermatids in porcine testes. The sex chromosomes were found at the nuclear edge in primary spermatocytes, which correlates with the known position of the XY body and their position in somatic cells, whereas, in spermatids, the sex chromosomes were much more centrally located, mirroring the position of these chromosomes in ejaculated spermatozoa. This study reveals the temporal repositioning of chromosome territories in spermatogenesis.
Synthesis and Structure of a Germylene Bearing a 1,8-Dimethoxyanthracene Ligand
Authors: Yamashita Makoto , Murakami Hiromi , Unrin-in Toshifumi , Kawachi Atsushi , Akiba Kin-ya , Yamamoto Yohsuke
Published: April 2005

A novel chlorogermylene compound, (1,8-dimethoxy-9-anthracenyl)chlorogermylene, has been synthesized by the reaction of GeCl2·dioxane and 9-lithio-1,8-dimethoxyanthracene. X-ray crystallographic study of the germylene revealed the bis-coordination of the oxygen atoms at the 1,8-positions to the germanium(II) center and the elongation of the Ge–Cl bond caused by the coordination.
Giver–receiver asymmetries in gift preferences
Authors: Teigen Karl Halvor , Olsen Marina V. G. , Solås Odd Egil
Published: April 2005

When people are asked to choose between gift items, givers and receivers sometimes show different patterns of preferences. The article reports four experimental studies exploring these giver–receiver asymmetries. Whereas givers tend to prefer exclusive, but smaller gift items, receivers appear to prefer less luxurious, and more useful gifts (Experiment 1). Givers prefer gift vouchers to cash, and are concerned about timing, whereas more receivers accept cash gifts, and claim that it does not matter if the gift arrives late (Experiment 2). One interpretation of the results could be that givers conform more strongly to gift conventions (cultural norms for gift exchange). It is further argued that these differences are not due to a perceived difference between self and others (Experiment 3), but rather because of situational differences. When receivers perform separate evaluations of gifts rather than joint evaluations (pairwise comparisons), they tend to change their preference pattern towards a higher rating of exclusive gift items (Experiment 4).
The generality of negative hierarchically restrictive behaviours
Authors: Brown Jennie , Trafimow David , Gregory W. Larry
Published: April 2005

Previous research has shown that when an actor engages in a negative hierarchically restrictive behaviour, a strong correspondent trait attribution is made and this behaviour is expected to generalize across situations (Trafimow, 2001). This paper discusses three experiments that examined the effects of extreme situations and perceived morality of the actor on the way in which participants make trait attributions, and the extent to which those behaviours are expected to generalize to other situations. Findings from Experiments 1 and 2 indicate that even negative hierarchically restrictive behaviours do not always lead to strong correspondent inferences if the situation in which the initial behaviour was performed was sufficiently extreme. Experiment 3 served to support these findings and cleared up questions from the first two experiments. Findings supported the hypothesis that some situations inhibit negative trait attributions and behaviour generalizations. Furthermore, findings indicate that the perception of the morality of the actor determines whether or not a negative hierarchically restrictive behaviour will lead to a negative trait attribution and generalization.
The subjective experience of partnership love: A Q Methodological study
Authors: Watts Simon , Stenner Paul
Published: April 2005

The social scientific literature seems increasingly to accept that defining partnership or ‘romantic’ love in a singular and timeless fashion might not be a realisable task (Fehr, 1988). One clearly discernible response to this situation takes the form of a turn towards studying the subjective experience of partnership love. The work ofMarston, Hecht, Manke, McDaniel, and Reeder (1998)andSternberg (1995,1996,1998)are highlighted as theoretical and methodological exemplars in this regard. Each successfully abstracts a range of cultural conceptions of partnership love from the subjective experiences of their participants. It is argued, however, that the subjective experiences of the participants themselves, and particularly the holistic or Gestalt nature of those experiences, are left behind in the process of abstraction. This new research seeks to rectify that situation. An alternative (but nonetheless related) approach to the study of partnership love is duly outlined and an illustrative Q‐Methodological study is reported which reveals eight distinct subjective experiences of partnership love at work amongst our participants (N=50). Each of these holistic experiences is presented in the form of a narrative account. These accounts are then discussed and situated in relation to existing academic, cultural and historical conceptions of partnership love.
Predictive models of implicit and explicit attitudes
Authors: Perugini Marco
Published: April 2005

Explicit attitudes have long been assumed to be central factors influencing behaviour. A recent stream of studies has shown that implicit attitudes, typically measured with the Implicit Association Test (IAT), can also predict a significant range of behaviours. This contribution is focused on testing different predictive models of implicit and explicit attitudes. In particular, three main models can be derived from the literature: (a) additive (the two types of attitudes explain different portion of variance in the criterion), (b) double dissociation (implicit attitudes predict spontaneous whereas explicit attitudes predict deliberative behaviour), and (c) multiplicative (implicit and explicit attitudes interact in influencing behaviour). This paper reports two studies testing these models. The first study (N=48) is about smoking behaviour, whereas the second study (N=109) is about preferences for snacks versus fruit. In the first study, the multiplicative model is supported, whereas the double dissociation model is supported in the second study. The results are discussed in light of the importance of focusing on different patterns of prediction when investigating the directive influence of implicit and explicit attitudes on behaviours.
Upward social comparison and self‐concept: Inspiration and inferiority among art students in an advanced programme
Authors: Burleson Kathryn , Leach Colin Wayne , Harrington David M.
Published: April 2005

We examined the role of social comparison in changes in the artistic self‐concept of adolescents attending an advanced arts programme. Unfavourable comparisons that promoted a sense of inferiority and favourable comparisons that promoted inspiration were measured just prior to, in the first week of, and at the end of the 6 week programme. Consistent with the ‘big fish little pond effect’, inferiority comparisons made during the programme were associated with negative changes in self‐concept. Consistent with the social comparison literature, however, inspiration comparisons made during the programme were associated with positive changes in self‐concept. Rather than suggesting that exposure to highly talented peers is necessarily unfavourable, results suggest that the interpretation of the comparisons made in situ determines the favourability of such exposure.
Children's category‐based inferences affect classification
Authors: Ross Brian H. , Gelman Susan A. , Rosengren Karl S.
Published: April 2005

Children learn many new categories and make inferences about these categories. Much work has examined how children make inferences on the basis of category knowledge. However, inferences may also affect what is learned about a category. Four experiments examine whether category‐based inferences during category learning influence category knowledge and thereby affect later classifications for 5‐ to 7‐year‐olds. The children learned to classify pictures of new types of creatures on the basis of a salient feature (colour) and then answered a question that required them to make an inference on the basis of other features. At test, children classified pictures that included only some features (without colour). Experiment 1 showed that the features relevant to the inference during learning led to better classification than did features irrelevant to the inference. Experiment 2 replicated this finding even when the relevant features were physically close to the irrelevant features. Experiments 3 and 4 found this effect even when the classification was learned prior to the inference task and even when no mention was made of the categories during inference learning. Taken together, these results show that making inferences during category learning can influence category knowledge and suggest a need to integrate the work on category learning and category‐based inferences.