bluuebunny/crossref_metadata_2025 huggingface dataset:
In the Shadow of the Khmer Rouge Tribunal: The Domestic Trials of Nuon Paet, Chhouk Rin and Sam Bith, and the Search for Judicial Legitimacy in Cambodia
Authors: Hall John
Published: November 2006

In 1994, Khmer Rouge guerrillas attacked a train in Kampot province, Cambodia, taking hostage three young Western backpackers. Two months later, after negotiations for their release collapsed, the three were murdered. Australian, British, and French government representatives exerted considerable diplomatic pressure on the Cambodian government, demanding that those responsible for the kidnapping and murders be brought to justice. In response, three former Khmer Rouge commanders, Chhouk Rin, Nuon Paet and Sam Bith, were arrested, and in a series of trials that lasted from 1999 until 2006, were convicted and sentenced to life imprisonment by Cambodian domestic courts.Crucially, these trials took place in the middle of difficult negotiations between Cambodia and the United Nations over the scope and nature of the proposed Khmer Rouge tribunal. A key point of disagreement was over the proper role in the tribunal for Cambodia's notoriously inefficient, corrupt and government-dominated judiciary. For that reason, the trials became a closely watched test of the Cambodian legal system, and took on a symbolic weight unusual for domestic trials. Dismissed by some observers as mere show trials aimed at legitimizing Prime Minister Hun Sen on the international stage, the trials nevertheless marked a significant step forward in the development of a functioning – albeit seriously flawed – judiciary.This article is the first to examine these highly significant cases. The Paet, Bith and Rin trials demonstrate the ability of Cambodian judges to convict Khmer Rouge members brought before them; what remains less clear is whether the Cambodian judicial appointees to the tribunal will be capable of meeting internationally recognized standards of justice. Perhaps, if permitted by their government to do so, they will grow to meet this historic challenge. If they do not, then the trials of Paet, Bith and Rin, may prove to be the high watermark in the search for judicial legitimacy in Cambodia.
Water Mass Distribution and Ventilation Time Scales in a Cost-Efficient, Three-Dimensional Ocean Model
Authors: Müller S. A. , Joos F. , Edwards N. R. , Stocker T. F.
Published: November 2006

A cost-efficient, seasonally forced three-dimensional frictional geostrophic balance ocean model (Bern3D) has been developed that features isopycnal diffusion and Gent–McWilliams transport parameterization, 32 depth layers, and an implicit numerical scheme for the vertical diffusion. It has been tuned toward observed chlorofluorocarbon (CFC-11) inventories and deep ocean radiocarbon signatures to reproduce the ventilation time scales of the thermocline and the deep ocean. Model results are consistent with the observed large-scale distributions of temperature, salinity, natural and bomb-produced radiocarbon, CFC-11, anthropogenic carbon, 39Ar/Ar, and estimates of the meridional heat transport. Root-mean-square errors for the temperature and salinity fields are 1 K and 0.2 psu, comparable to results from the Ocean Carbon-Cycle Model Intercomparison Project. Global inventories of CFC-11 and anthropogenic carbon agree closely with observation-based estimates. Model weaknesses include a too-weak formation and propagation of Antarctic Intermediate Water and of North Atlantic Deep Water. The model has been applied to quantify the recent carbon balance, surface-to-deep transport mechanisms, and the importance of vertical resolution for deep equatorial upwelling. Advection is a dominant surface-to-deep transport mechanism, whereas explicit diapycnal mixing is of little importance for passive tracers and contributes less than 3% to the modeled CFC-11 inventory in the Indo-Pacific. Decreasing the vertical resolution from 32 to 8 layers causes deep equatorial upwelling to increase by more than a factor of 4. Modeled ocean uptake of anthropogenic carbon is 19.7 GtonC over the decade from 1993 to 2003, comparable to an estimate from atmospheric oxygen data of 22.4 ± 6.1 GtonC.
Variability of the Winter Wind Waves and Swell in the North Atlantic and North Pacific as Revealed by the Voluntary Observing Ship Data
Authors: Gulev Sergey K. , Grigorieva Vika
Published: November 2006

This paper analyses secular changes and interannual variability in the wind wave, swell, and significant wave height (SWH) characteristics over the North Atlantic and North Pacific on the basis of wind wave climatology derived from the visual wave observations of voluntary observing ship (VOS) officers. These data are available from the International Comprehensive Ocean–Atmosphere Data Set (ICOADS) collection of surface meteorological observations for 1958–2002, but require much more complicated preprocessing than standard meteorological variables such as sea level pressure, temperature, and wind. Visual VOS data allow for separate analysis of changes in wind sea and swell, as well as in significant wave height, which has been derived from wind sea and swell estimates. In both North Atlantic and North Pacific midlatitudes winter significant wave height shows a secular increase from 10 to 40 cm decade−1 during the last 45 yr. However, in the North Atlantic the patterns of trend changes for wind sea and swell are quite different from each other, showing opposite signs of changes in the northeast Atlantic. Trend patterns of wind sea, swell, and SWH in the North Pacific are more consistent with each other. Qualitatively the same conclusions hold for the analysis of interannual variability whose leading modes demonstrate noticeable differences for wind sea and swell. Statistical analysis shows that variability in wind sea is closely associated with the local wind speed, while swell changes can be driven by the variations in the cyclone counts, implying the importance of forcing frequency for the resulting changes in significant wave height. This mechanism of differences in variability patterns of wind sea and swell is likely more realistic than the northeastward propagation of swells from the regions from which the wind sea signal originates.
Modeling Displacement Properties of Immiscible Fluids in Porous Media
Authors: Unsal Evren , Dane Jacob H. , Schwartz Peter , Dozier Gerry V.
Published: November 2006

Fluid transport through porous structures is a subject of active research, both theoretically and experimentally. In this article, the authors provide a modified model of flow that gives a detailed description of fluid penetration through hydrophobic, nonwoven networks. The porous medium was modeled as parallel cylindrical capillaries in two different ways: one with uniform diameters across the capillary length, referred to as the “capillary model”, and a modified version with sections of different diameters across the capillary length, called the “ink-bottle model”. To validate the numerical results, an experimental methodology was also developed. The methodology made use of a pressure/flow cell in which the sample was mounted. The flow rates were measured during sequences of increasing and decreasing pressures applied to the displacing nonwetting fluid (aqueous solution). The ink-bottle model reproduced all the wetting patterns that were observed in the experiments, while the capillary model was able to capture only the patterns observed during the initial contact of the fabric with the solution.
Shared State Synchronization for HLA-Based Distributed Simulation
Authors: Low Malcolm Yoke Hean , Gan Boon Ping , Wei Junhu , Wang Xiaoguang , Turner Stephen John , Cai Wentong
Published: November 2006

The problem of shared state is well known to the parallel and distributed simulation research community. In this article, the authors revisit the problem of shared state in the context of a High Level Architecture (HLA)-based distributed simulation. A middleware approach is proposed to solve this problem within the framework of the HLA runtime infrastructure. Four solutions to this problem are implemented in the middleware using receive-order messages. The authors discuss the implementation issues of these four solutions in the middleware. Experimental results comparing the performance of these four solutions against a simple request-reply approach using timestamp-order messages are also presented.
A Simplified Model for the Melting of Polymer Pellets under Compression in a Twin-Screw Extruder
Authors: Zhu Linjie , Narh K. A.
Published: November 2006

Plastic energy dissipation (PED) is an important mechanism involving the melting of polymer in a twin-screw extruder. In the present study, the melting behavior of polymer pellets under compression is studied by a simplified model with the finite element method, based on the fact that mechanical energy from the deformation of a single pellet is converted into heat energy. The model shows that the heating of the pellet is not uniform. Under compression, the contact area of the pellet yields first, and the deformation in the pellet depends on the compression ratio and properties of the pellet. The simulated results show that the temperature in the volume around the line passing through the contacting point and the center of the pellet is higher than the temperature further from the contact area.
An Approach to Model Network Exploitations Using Exploitation Graphs
Authors: Li Wei , Vaughn Rayford B. , Dandass Yoginder S.
Published: November 2006

In this article, a modeling process is defined to address challenges in analyzing attack scenarios and mitigating vulnerabilities in networked environments. Known system vulnerability data, system configuration data, and vulnerability scanner results are considered to create exploitation graphs ( e-graphs) that are used to represent attack scenarios. Experiments carried out in a cluster computing environment showed the usefulness of proposed techniques in providing in-depth attack scenario analyses for security engineering. Critical vulnerabilities can be identified by employing graph algorithms. Several factors were used to measure the difficulty in executing an attack. A cost/benefit analysis was used for more accurate quantitative analysis of attack scenarios. The authors also show how the attack scenario analyses better help deployment of security products and design of network topologies.
Accelerating Missile Threat Simulations Using Personal Computer Graphics Cards
Authors: Jeffers Sean A. , Baldwin Rusty O. , Mullins Barry E.
Published: November 2006

The authors use inexpensive personal computer graphics cards to perform the intensive image-processing computations done in a heat-seeking missile’s tracking systems and thereby dramatically reduce the execution time of missile threat simulations used by military mission planners. Using an innovative processing algorithm, these calculations are accomplished up to 3.5 times faster in graphic cards versus using a conventional CPU. Through a combination of this and other software optimizations, simulation time was reduced by 33%.
Roles in the e-landscape
Authors: Abell Angela , Chapman Darron , Phillips Peter , Stewart Helen , Ward Sandra
Published: November 2006

Based on a programme of activities undertaken between January 2005 and June 2006, including a research project, TFPL has produced a white paper about the e-information job market and a roles framework. It suggests that the e-information job market reflects the development of new technologies but is driven by corporate imperatives resulting from the utilization of these technologies. These drivers fuel a need for e-information professionals who know how to deliver information for particular applications to communities familiar with the convenience of the services offered by Google and Amazon; and who are able to ensure that information supports organizational goals. The roles include an increase in ‘traditional’ information roles, as well as the creation of new employment opportunities. Current and emerging roles can be clustered into six role families and also categorized as back-office or front-office focused. This article reflects the content of the white paper and the findings of the research.
Creativity and innovation
Authors: Heye Dennie
Published: November 2006

Argues that 21st century information professionals need characteristics of creativity and innovation to remain relevant. Suggests that these do not threaten the profession but are a driver to its becoming a key information player. Defines the two terms and explains that they are linked. Suggests that it is possible to develop creative skills without necessarily feeling creative, and to facilitate sessions where creativity is needed. Includes advice on a range of creative techniques for encouraging ideas, including risk taking, visualizing, daydreaming, SWOT analysis, brainstorming, learning from mistakes and extending one’s circle of contacts to obtain a fresh view of the problem.
Roadmap for the future-where to next?
Authors: Marfleet Jackie
Published: November 2006

Describes the work of the British Library Business and Intellectual Property Centre, which was launched with the Library’s first above the line marketing campaign. Explains the challenges of providing a national service to businesses although physically based in London, and designing a range of new services to meet user needs. Covers the workshops programme, the ‘Ask an Expert’ sessions, and the forthcoming information advice and consultation service. Describes the Library’s business and intellectual property collections, including its electronic resources, online enquiry service and website. Also covers the evening events for entrepreneurs and the fee-based research service.
Psychometric Testing of the Chinese Version of the Decisional Balance Scale (CDBS)
Authors: Chen Huey-Shys , Sheu Jiunn-Jye , Chen W. William
Published: November 2006

The purpose of this study was to conduct psychometric testing on the Chinese version of the decisional balance scale (CDBS) with Taiwanese seventh, eighth,and ninth graders who were recruitedfrom the Taipei metropolitan area. A random cluster sampling method was used with 554 adolescents between the ages of 13 and 17 years. Factor analysis procedures showed two components, Pros and Cons, accounting for 74.32% of the total variances andcontrastedgroupcomparisonsaffirmedthe constructvalidityof the Pros, the Cons, andthe CDBS. Item-to-subtotalcorrelationcoefficients for the two subscales, the Pros and Cons, were greater than .50 and their reliability was supported by Cronbach's alpha coefficients, .87 and .91, respectively. The validity and reliability of the CDBS suggestedthat the CDBS was applicableto and congruentwith the culture of the Taiwanese adolescent's smoking behavior. Further validation of the CDBS scale with different populations and larger sample size is suggested.
Learning About Sex: Results From Natsal 2000
Authors: Macdowall Wendy , Wellings Kaye , Mercer Catherine H. , Nanchahal Kiran , Copas Andrew J. , McManus Sally , Fenton Kevin A. , Erens Bob , Johnson Anne M.
Published: November 2006

To date, the focus of sex education research has tended to be on the effect of education on behavioral outcomes. There is little data on the felt needs of young people, how well they are met, and how provision might be improved. Here we report on main source of information about sexual matters, adequacy of knowledge, further needs, and preferred source of additional information, using data from a probability sample survey of people aged 16 to 44 years in Britain (Natsal 2000). A total of 11,161 participants (4,762 men and 6,399 women) were interviewed. The response rate was 65.4%. The results show that despite the assumed worldliness and sophistication of young people about sexual matters, there is a great deal of self-perceived ignorance among them. Parents and schools are the preferred source of further information. We need to enable parents to provide information to their children, especially their sons.
von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins
Authors: Chauhan Anil K. , Kisucka Janka , Lamb Colin B. , Bergmeier Wolfgang , Wagner Denisa D.
Published: November 2006

von Willebrand factor (VWF) protects factor VIII (FVIII) from proteolysis and mediates the initial contact of platelets with the injured vessel wall, thus playing an important role in hemostasis and thrombosis. VWF is crucial for the formation of occlusive thrombi at arterial shear rates. However, with only a few conflicting studies published, the role of VWF in venous thrombosis is still unclear. Using gene-targeted mice, we show that in ferric chloride–injured veins platelet adhesion to subendothelium is decreased and thrombus growth is impaired in VWF−/− mice when compared with wild type (WT). We also observed increased embolization in the VWF−/− mice, which was due to lower FVIII levels in these mice as recombinant factor VIII (r-FVIII) restored thrombus stability. Despite normalization of blood clotting time and thrombus stability after r-FVIII infusion, the VWF−/− venules did not occlude. Transgenic platelets lacking the VWF receptor GPIbα extracellular domain showed decreased adhesion to injured veins. But, after a delay, all the injured venules occluded in these transgenic mice. Thus, VWF likely uses other adhesion receptors besides GPIbα in thrombus growth under venous shear conditions. Our studies document crucial roles for VWF and FVIII in experimental thrombosis under venous flow conditions in vivo.
Late cardiotoxicity after treatment for Hodgkin lymphoma
Authors: Aleman Berthe M. P. , van den Belt-Dusebout Alexandra W. , De Bruin Marie L. , van 't Veer Mars B. , Baaijens Margreet H. A. , Boer Jan Paul de , Hart Augustinus A. M. , Klokman Willem J. , Kuenen Marianne A. , Ouwens Gabey M. , Bartelink Harry , van Leeuwen Flora E.
Published: November 2006

We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios [SIRs] = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.
Ultrastructural analysis of development of myocardium in calreticulin-deficient mice
Authors: Lozyk Mira D , Papp Sylvia , Zhang Xiaochu , Nakamura Kimitoshi , Michalak Marek , Opas Michal
Published: November 2006

Background

Calreticulin is a Ca2+binding chaperone of the endoplasmic reticulum which influences gene expression and cell adhesion. The levels of both vinculin and N-cadherin are induced by calreticulin expression, which play important roles in cell adhesiveness. Cardiac development is strictly dependent upon the ability of cells to adhere to their substratum and to communicate with their neighbours.

Results

We show here that the levels of N-cadherin are downregulated in calreticulin-deficient mouse embryonic hearts, which may lead to the disarray and wavy appearance of myofibrils in these mice, which we detected at all investigated stages of cardiac development. Calreticulin wild type mice exhibited straight, thick and abundant myofibrils, which were in stark contrast to the thin, less numerous, disorganized myofibrils of the calreticulin-deficient hearts. Interestingly, these major differences were only detected in the developing ventricles while the atria of both calreticulin phenotypes were similar in appearance at all developmental stages. Glycogen also accumulated in the ventricles of calreticulin-deficient mice, indicating an abnormality in cardiomyocyte metabolism.

Conclusion

Calreticulin is temporarily expressed during heart development where it is required for proper myofibrillogenesis. We postulate that calreticulin be considered as a novel cardiac fetal gene.
Temporal and spatial control of transgene expression using laser induction of the hsp70promoter
Authors: Ramos Diane M , Kamal Firdous , Wimmer Ernst A , Cartwright Alexander N , Monteiro Antónia
Published: November 2006

Background

Precise temporal and spatial regulation of transgene expression is a critical tool to investigate gene function in developing organisms. The most commonly used technique to achieve tight control of transgene expression, however, requires the use of specific DNA enhancers that are difficult to characterize in non-model organisms. Here, we sought to eliminate the need for this type of sequence-based gene regulation and to open the field of functional genetics to a broader range of organisms.

Results

We have developed a new laser mediated method to heat shock groups of cells that provides precise spatio-temporal control of gene expression without requiring knowledge of specific enhancer sequences. We tested our laser-system in a transgenic line of Bicyclus anynana butterflies containing the EGFP reporter gene attached to the heat sensitive hsp70 promoter of Drosophila melanogaster. Whole organismal heat shocks demonstrated that this Drosophila promoter can drive gene expression in butterflies, and the subsequent laser heat shocks showed that it was possible to activate cell-specific gene expression in very precise patterns on developing pupal wings.

Conclusion

This laser-mediated gene expression system will enable functional genetic investigations, i.e., the ectopic expression of genes and their knock-down in targeted groups of cells in model and non-model organisms with little or no available regulatory data, as long as a compatible heat-shock promoter is used and the target tissue is accessible to a laser beam. This technique will also be useful in evolutionary developmental biology as it will enable the study of the evolution of gene function across a variety of organisms.
Sensory defects in Necdin deficient mice result from a loss of sensory neurons correlated within an increase of developmental programmed cell death
Authors: Andrieu David , Meziane Hamid , Marly Fabienne , Angelats Corinne , Fernandez Pierre-Alain , Muscatelli Françoise
Published: November 2006

Background

The humanNECDINgene is involved in a neurodevelopmental disorder, Prader-Willi syndrome (PWS). Previously we reported a mouse Necdin knock-out model with similar defects to PWS patients. Despite the putative roles attributed to Necdin, mainly fromin vitrostudies, itsin vivofunction remains unclear. In this study, we investigate sensory-motor behaviour in Necdin deficient mice. We reveal cellular defects and analyse their cause.

Results

We report sensory differences in Necdin deficient mice compared to wild type animals. These differences led us to investigate sensory neuron development in Necdin deficient mouse embryos. First, we describe the expression pattern of Necdin in developing DRGs and report a reduction of one-third in specified sensory neurons in dorsal roots ganglia and show that this neuronal loss is achieved by E13.5, when DRGs sensory neurons are specified. In parallel, we observed an increase of 41% in neuronal apoptosis during the wave of naturally occurring cell death at E12.5. Since it is assumed that Necdin is a P75NTR interactor, we looked at the P75NTR-expressing cell population in Necdin knock-out embryos. Unexpectedly, Necdin loss of function has no effect on p75NTR expressing neurons suggesting no direct genetic interaction between Necdin and P75NTR in this context.

Although we exclude a role of Necdin in axonal outgrowth from spinal sensory neurons in early developmental stages; such a role could occur later in neuronal differentiation. Finally we also exclude an anti-proliferative role of Necdin in developing sensory neurons.

Conclusion

Overall, our data show clearly that, in early development of the nervous system, Necdin is an anti-apoptotic or survival factor.
Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases
Authors: Nicolini Andrea , Tartarelli Gianna , Carpi Angelo , Metelli Maria Rita , Ferrari Paola , Anselmi Loretta , Conte Massimo , Berti Piero , Miccoli Paolo
Published: November 2006

Background

In breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel.

Methods

In 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, ≥ 11 and ≥ 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels.

Results

Distant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off ≥ 11 U/mL, MCA showed the lowest specificity (42%); with cut-off ≥ 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With ≥ 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With ≥ 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel.

Conclusion

At both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients.
Smoking trends among adolescents from 1990 to 2002 in ten European countries and Canada
Authors: Hublet Anne , De Bacquer Dirk , Valimaa Raili , Godeau Emmanuelle , Schmid Holger , Rahav Giora , Maes Lea
Published: November 2006

Background

Daily smoking adolescents are a public health problem as they are more likely to become adult smokers and to develop smoking-related health problems later on in their lives.

Methods

The study is part of the four-yearly, cross-national Health Behaviour in School-aged Children study, a school-based survey on a nationally representative sample using a standardised methodology. Data of 4 survey periods are available (1990–2002). Gender-specific daily smoking trends among 14–15 year olds are examined using logistic regressions. Sex ratios are calculated for each survey period and country. Interaction effects between period and gender are examined.

Results

Daily smoking prevalence in boys in 2002 ranges from 5.5% in Sweden to 20.0% in Latvia. Among girls, the daily smoking prevalence in 2002 ranges from 8.9% in Poland to 24.7% in Austria. Three daily smoking trend groups are identified: countries with a declining or stagnating trend, countries with an increasing trend followed by a decreasing trend, and countries with an increasing trend. These trend groups show a geographical pattern, but are not linked to smoking prevalence. Over the 4 surveys, the sex ratio has changed in Belgium, Switzerland, and Latvia.

Conclusion

Among adolescents in Europe, three groups of countries in a different stage of the smoking epidemic curve can be identified, with girls being in an earlier stage than boys. In 2002, large differences in smoking prevalence between the countries have been observed. This predicts a high mortality due to smoking over 20–30 years for some countries, if no policy interventions are taken.
Dexamethasone stimulates expression of C-type Natriuretic Peptide in chondrocytes
Authors: Agoston Hanga , Baybayan Laurie , Beier Frank
Published: November 2006

Background

Growth of endochondral bones is regulated through the activity of cartilaginous growth plates. Disruption of the physiological patterns of chondrocyte proliferation and differentiation – such as in endocrine disorders or in many different genetic diseases (e.g. chondrodysplasias) – generally results in dwarfism and skeletal defects. For example, glucocorticoid administration in children inhibits endochondral bone growth, but the molecular targets of these hormones in chondrocytes remain largely unknown. In contrast, recent studies have shown that C-type Natriuretic Peptide (CNP) is an important anabolic regulator of cartilage growth, and loss-of-function mutations in the human CNP receptor gene cause dwarfism. We asked whether glucocorticoids could exert their activities by interfering with the expression of CNP or its downstream signaling components.

Methods

Primary mouse chondrocytes in monolayer where incubated with the synthetic glucocorticoid Dexamethasone (DEX) for 12 to 72 hours. Cell numbers were determined by counting, and real-time PCR was performed to examine regulation of genes in the CNP signaling pathway by DEX.

Results

We show that DEX does influence expression of key genes in the CNP pathway. Most importantly, DEX significantly increases RNA expression of the gene encoding CNP itself (Nppc). In addition, DEX stimulates expression ofPrkg2(encoding cGMP-dependent protein kinase II) andNpr3(natriuretic peptide decoy receptor) genes. Conversely, DEX was found to down-regulate the expression of the gene encoding its receptor,Nr3c1(glucocorticoid receptor), as well as theNpr2gene (encoding the CNP receptor).

Conclusion

Our data suggest that the growth-suppressive activities of DEX are not due to blockade of CNP signaling. This study reveals a novel, unanticipated relationship between glucocorticoid and CNP signaling and provides the first evidence that CNP expression in chondrocytes is regulated by endocrine factors.
Evaluating complementary and alternative medicine interventions: in search of appropriate patient-centered outcome measures
Authors: Verhoef Marja J , Vanderheyden Laura C , Dryden Trish , Mallory Devon , Ware Mark A
Published: November 2006

Background

Central to the development of a sound evidence base for Complementary and Alternative Medicine (CAM) interventions is the need for valid, reliable and relevant outcome measures to assess whether the interventions work. We assessed the specific needs for a database that would cover a wide range of outcomes measures for CAM research and considered a framework for such a database.

Methods

The study was a survey of CAM researchers, practitioners and students. An online questionnaire was emailed to the members of the Canadian Interdisciplinary Network for CAM Research (IN-CAM) and the CAM Education and Research Network of Alberta (CAMera). The majority of survey questions were open-ended and asked about outcome measures currently used, outcome measures' assessment criteria, sources of information, perceived barriers to finding outcome measures and outcome domains of importance. Descriptive quantitative analysis and qualitative content analysis were used.

Results

One hundred and sixty-four completed surveys were received. Of these, 62 respondents reported using outcome measures in their CAM research and identified 92 different specific outcomes. The most important barriers were the fact that, for many health concepts, outcome measures do not yet exist, as well as issues related to accessibility of instruments. Important outcome domains identified included physical, psychological, social, spiritual, quality of life and holistic measures. Participants also mentioned the importance of individualized measures that assess unique patient-centered outcomes for each research participant, and measures to assess the context of healing and the process of healing.

Conclusion

We have developed a preliminary framework that includes all components of health-related outcomes. The framework provides a foundation for a larger, comprehensive collection of CAM outcomes. It fits very well in a whole systems perspective, which requires an expanded set of outcome measures, such as individualized and holistic measures, with attention to issues of process and context.
Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia
Authors: Gebru Tamirat , Hailu Asrat , Kremsner Peter G , Kun Jürgen FJ , Grobusch Martin P
Published: November 2006

Background

Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone®) and inhibits the cytochrome bc1 complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding site resulting in a reduced binding affinity of atovaquone for plasmodial cytochrome b, thus resulting in drug resistance.

Methods

The prevalence of cytochrome b point mutations possibly conferring atovaquone resistance in Plasmodium falciparum isolates in atovaquone treatment-naïve patient cohorts from Lambaréné, Gabon and from South Western Ethiopia was assessed.

Results

Four/40 (10%) mutant types (four different single polymorphisms, one leading to an amino acid change from M to I in a single case) in Gabonese isolates, but all 141/141 isolates were wild type in Ethiopia were found.

Conclusion

In the absence of drug pressure, spontaneous and possibly resistance-conferring mutations are rare.
A self-inactivating retrovector incorporating the IL-2 promoter for activation-induced transgene expression in genetically engineered T-cells
Authors: Jaalouk Diana E , Lejeune Laurence , Couture Clément , Galipeau Jacques
Published: November 2006

Background

T-cell activation leads to signaling pathways that ultimately result in induction of gene transcription from the interleukin-2 (IL-2) promoter. We hypothesized that the IL-2 promoter or its synthetic derivatives can lead to T-cell specific, activation-induced transgene expression. Our objective was to develop a retroviral vector for stable and activation-induced transgene expression in T-lymphocytes.

Results

First, we compared the transcriptional potency of the full-length IL-2 promoter with that of a synthetic promoter composed of 3 repeats of the Nuclear Factor of Activated T-Cells (NFAT) element following activation of transfected Jurkat T-cells expressing the large SV40 T antigen (Jurkat TAg). Although the NFAT3 promoter resulted in a stronger induction of luciferase reporter expression post stimulation, the basal levels of the IL-2 promoter-driven reporter expression were much lower indicating that the IL-2 promoter can serve as a more stringent activation-dependent promoter in T-cells. Based on this data, we generated a self-inactivating retroviral vector with the full-length human IL-2 promoter, namely SINIL-2pr that incorporated the enhanced green fluorescent protein (EGFP) fused to herpes simplex virus thymidine kinase as a reporter/suicide "bifunctional" gene. Subsequently, Vesicular Stomatitis Virus-G Protein pseudotyped retroparticles were generated for SINIL-2pr and used to transduce the Jurkat T-cell line and the ZAP-70-deficient P116 cell line. Flow cytometry analysis showed that EGFP expression was markedly enhanced post co-stimulation of the gene-modified cells with 1 μM ionomycin and 10 ng/ml phorbol 12-myristate 13-acetate (PMA). This activation-induced expression was abrogated when the cells were pretreated with 300 nM cyclosporin A.

Conclusion

These results demonstrate that the SINIL-2pr retrovector leads to activation-inducible transgene expression in Jurkat T-cell lines. We propose that this design can be potentially exploited in several cellular immunotherapy applications.
Luminal concentrations of L- and D-lactate in the rectum may relate to severity of disease and outcome in septic patients
Authors: Jørgensen Vibeke L , Reiter Nanna , Perner Anders
Published: November 2006

Introduction

Little is known about the condition of the large bowel in patients with sepsis. We have previously demonstrated increased concentrations of L-lactate in the rectal lumen in patients with abdominal septic shock. The present study was undertaken to assess the concentrations of L- and D-lactate in rectal lumen and plasma in septic patients including the possible relation to site of infection, severity of disease, and outcome.

Methods

An intensive care unit observational study was conducted at two university hospitals, and 23 septic patients and 11 healthy subjects were enrolled. Participants were subjected to rectal equilibrium dialysis, and concentrations of L- and D-lactate in dialysates and plasma were analysed by spectrophotometry.

Results

Luminal concentrations of L-lactate in rectum were related to the sequential organ failure assessment scores (R2 = 0.27, P = 0.01) and were higher in non-survivors compared to survivors and healthy subjects (mean [range] 5.0 [0.9 to 11.8] versus 2.2 [0.4 to 4.9] and 0.5 [0 to 1.6] mmol/l, respectively, P < 0.0001), with a positive linear trend (R2 = 0.53, P < 0.0001). Also, luminal concentrations of D-lactate were increased in non-survivors compared to survivors and healthy subjects (1.1 [0.3 to 2.5] versus 0.3 [0 to 1.2] and 0.1 [0 to 0.8] mmol/l, respectively, P = 0.01), with a positive linear trend (R2 = 0.14, P = 0.04). Luminal concentrations of L- and D-lactate were unaffected by the site of infection. Plasma concentrations of L-lactate were also increased in non-survivors compared to survivors (3.8 [1.7 to 7.0] versus 1.5 [0 to 3.6] mmol/l, P < 0.01). In contrast, plasma concentrations of D-lactate were equally raised in non-survivors (0.4 [0.1 to 0.7] mmol/l) and survivors (0.3 [0.1 to 0.6] mmol/l) compared with healthy subjects (0.03 [0 to 0.13] mmol/l).

Conclusion

In patients with severe sepsis and septic shock, luminal concentrations of L- and D-lactate in the rectum were related to severity of disease and outcome.
Cancer Mortality in an Area of Campania (Italy) Characterized by Multiple Toxic Dumping Sites
Authors: COMBA PIETRO , BIANCHI FABRIZIO , FAZZO LUCIA , MARTINA LUCIA , MENEGOZZO MASSIMO , MINICHILLI FABRIZIO , MITIS FRANCESCO , MUSMECI LOREDANA , PIZZUTI RENATO , SANTORO MICHELE , TRINCA STEFANIA , MARTUZZI MARCO ,   “Health Impact of Waste Management Campania” Working Group
Published: November 2006

Abstract:  Several recent studies have documented that a widespread practice of dumping toxic wastes has taken place for many years in the Provinces of Naples and Caserta. Extensive programs of environmental monitoring are currently ongoing in the area. In this frame, the Department of Civil Defence of the Italian Government has appointed an ad hoc study group in order to assess the health status of the population resident in the area of interest. The first investigation performed by the study group has been a geographic study on cancer mortality and occurrence of malformations in 196 municipalities constituting the two Provinces. The study detected an area located in the southeastern part of the Province of Caserta and in the northwestern part of the Province of Naples, where cancer mortality and congenital malformations show significantly increased rates with respect to expected figures derived from the regional population. The area highlighted by the study is, in general terms, overlapping with the area where most illegal dumping of toxic wastes took place. It is now recommended that mortality studies be extended to take into account other health outcomes, to search for correlations with environmental exposures, and consider possible confounding factors.
Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer
Authors: Haffty Bruce G. , Yang Qifeng , Reiss Michael , Kearney Thomas , Higgins Susan A. , Weidhaas Joanne , Harris Lyndsay , Hait Willam , Toppmeyer Deborah
Published: November 2006

Purpose

To determine the prognostic significance of triple negative breast cancers with respect to locoregional relapse and distant metastasis in conservatively managed breast cancer patients.

Patients and Methods

A database of conservative managed (conservative surgery followed by radiation) patients, in whom all three markers (estrogen receptor, progesterone receptor, and HER2/neu) were available, was reviewed. Patients were classified as triple negative if they tested negative for all three markers. Of 482 patients with all three markers available, 117 were classified as triple negative.

Results

As of September 2005, with a median follow-up time of 7.9 years, of the 482 patients in the study, there have been 53 in-breast relapses, 10 nodal relapses, 77 distant relapses, and 69 deaths. At 5 years, the triple negative cohort had a poorer distant metastasis-free rate compared with the other subtypes (67% v 82%, respectively; P = .002). Triple negative subtype was an independent predictor of distant metastasis (hazard ratio = 2.14; 95% CI, 1.31 to 3.53; P = .002) and cause-specific survival (hazard ratio = 1.79; 95% CI, 1.03 to 3.22; P = .047). There was no significant difference in local control between the triple negative and other subtypes (83% v 83%, respectively). Of 99 BRCA-tested patients in this cohort, 10 had deleterious mutations in BRCA1, and seven had mutations in BRCA2. Of 10 BRCA1 patients, eight were triple negative, whereas only one of seven BRCA2 patients was triple negative (P < .001).

Conclusion

Patients classified as triple negative have a poor prognosis. However, there was no evidence that these patients are at higher risk for local relapse after conservative surgery and radiation. Patients with BRCA1 mutations develop predominantly triple negative tumors.
How Known Constructions Influence the Acquisition of Other Constructions: The German Passive and Future Constructions
Authors: Abbot‐Smith Kirsten , Behrens Heike
Published: November 2006

This article suggests evidence for and reasons why prior acquisition may either facilitate or inhibit acquisition of a new construction. It investigates acquisition of the German passive and future constructions which contain a lexical verb with either the auxiliary sein “to be” or werden “to become”, and are related through these to potential supporting constructions. We predicted that a supported construction should be acquired earlier, faster, and unusually rapidly. An inhibited construction should show an extended depressed usage. We analyzed a dense corpus of a German boy between 2;0 and 5;0. He acquired the sein‐ before the werden‐passive. The former was supported by his prior acquisition of the sein copula, whereas the werden‐passive itself supported one werden copula construction. He acquired the werden‐future extremely slowly due to the hindrance of a semantically identical construction. These results fit with an emergentist approach in which apparently “sudden” acquisition is still due to gradual learning mechanisms.
The Action–Sentence Compatibility Effect: It's All in the Timing
Authors: Borreggine Kristin L. , Kaschak Michael P.
Published: November 2006

When participants are asked to make sensibility judgments on sentences that describe action toward the body (i.e., “Mark dealt the cards to you”) or away from the body (i.e., “You dealt the cards to Mark”), they are faster to respond when the response requires an arm movement in the same direction as the action described by the sentence. This congruence effect is known as the Action–Sentence Compatibility Effect (ACE). This study reports 4 experiments that extend our understanding of the ACE by exploring how the time at which one prepares the motor response required for the sensibility judgment affects the magnitude of the ACE. Results show that the ACE arises only when participants have the opportunity to plan their motor response while they are processing the sentence.
The divergent TGF-β ligand Dawdle utilizes an activin pathway to influence axon guidance inDrosophila
Authors: Parker Louise , Ellis Jeremy E. , Nguyen Minh Q. , Arora Kavita
Published: November 2006

Axon guidance is regulated by intrinsic factors and extrinsic cues provided by other neurons, glia and target muscles. Dawdle (Daw), a divergent TGF-β superfamily ligand expressed in glia and mesoderm, is required for embryonic motoneuron pathfinding in Drosophila. In dawmutants, ISNb and SNa axons fail to extend completely and are unable to innervate their targets. We find that Daw initiates an activin signaling pathway via the receptors Punt and Baboon (Babo) and the signal-transducer Smad2. Furthermore, mutations in these signaling components display similar axon guidance defects. Cell-autonomous disruption of receptor signaling suggests that Babo is required in motoneurons rather than in muscles or glia. Ectopic ligand expression can rescue the daw phenotype, but has no deleterious effects. Our results indicate that Daw functions in a permissive manner to modulate or enable the growth cone response to other restricted guidance cues,and support a novel role for activin signaling in axon guidance.
T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration
Authors: Song Mi-Ryoung , Shirasaki Ryuichi , Cai Chen-Leng , Ruiz Esmeralda C. , Evans Sylvia M. , Lee Soo-Kyung , Pfaff Samuel L.
Published: November 2006

Members of the T-box transcription factor family (Tbx) are associated with several human syndromes during embryogenesis. Nevertheless, their functions within the developing CNS remain poorly characterized. Tbx20 is expressed by migrating branchiomotor/visceromotor (BM/VM) neurons within the hindbrain during neuronal circuit formation. We examined Tbx20 function in BM/VM cells using conditional Tbx20-null mutant mice to delete the gene in neurons. Hindbrain rhombomere patterning and the initial generation of post-mitotic BM/VM neurons were normal in Tbx20 mutants. However,Tbx20 was required for the tangential (caudal) migration of facial neurons,the lateral migration of trigeminal cells and the trans-median movement of vestibuloacoustic neurons. Facial cell soma migration defects were associated with the coordinate downregulation of multiple components of the planar cell polarity pathway including Fzd7, Wnt11, Prickle1, Vang1 and Vang2. Our study suggests that Tbx20 programs a variety of hindbrain motor neurons for migration, independent of directionality, and in facial neurons is a positive regulator of the non-canonical Wnt signaling pathway.