In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatment with trastuzumab/erlotinib or lapatinib alone: implication of receptors' down-regulation and dimers' disruption.

We previously demonstrated the synergistic therapeutic effect of the cetuximab (anti-epidermal growth factor receptor [EGFR] monoclonal antibody, mAb)-trastuzumab (anti-HER2 mAb) combination (2mAbs therapy) in HER2(low) human pancreatic carcinoma xenografts. Here, we compared the 2mAbs therapy, the erlotinib (EGFR tyrosine kinase inhibitor [TKI])-trastuzumab combination and lapatinib alone (dual HER2/EGFR TKI) and explored their possible mechanisms of action. The effects on tumor growth and animal survival of the three therapies were assessed in nude mice xenografted with the human pancreatic carcinoma cell lines Capan-1 and BxPC-3. After therapy, EGFR and HER2 expression and AKT phosphorylation in tumor cells were analyzed by Western blot analysis. EGFR/HER2 heterodimerization was quantified in BxPC-3 cells by time-resolved FRET. In K-ras-mutated Capan-1 xenografts, the 2mAbs therapy gave significantly higher inhibition of tumor growth than the erlotinib/trastuzumab combination, whereas in BxPC-3 (wild-type K-ras) xenografts, the erlotinib/trastuzumab combination showed similar growth inhibition but fewer tumor-free mice. Lapatinib showed no antitumor effect in both types of xenografts. The efficacy of the 2mAbs therapy was partly Fc-independent because F(ab')(2) fragments of the two mAbs significantly inhibited BxPC-3 growth, although with a time-limited therapeutic effect. The 2mAbs therapy was associated with a reduction of EGFR and HER2 expression and AKT phosphorylation. BxPC-3 cells preincubated with the two mAbs showed 50% less EGFR/HER2 heterodimers than controls. In pancreatic carcinoma xenografts, the 2mAbs therapy is more effective than treatments involving dual EGFR/HER2 TKIs. The mechanism of action may involve decreased AKT phosphorylation and/or disruption of EGFR/HER2 heterodimerization.

Cadmium-free quantum dots in aqueous solution: potential for fingermark detection, synthesis and an application to the detection of fingermarks in blood on non-porous surfaces

The use of quantum dots (QDs) in the area of fingermark detection is currently receiving a lot of attention in the forensic literature. Most of the research efforts have been devoted to cadmium telluride (CdTe) quantum dots often applied as powders to the surfaces of interests. Both the use of cadmium and the nano size of these particles raise important issues in terms of health and safety. This paper proposes to replace CdTe QDs by zinc sulphide QDs doped with copper (ZnS:Cu) to address these issues. Zinc sulphide-copper doped QDs were successfully synthesized, characterized in terms of size and optical properties and optimized to be applied for the detection of impressions left in blood, where CdTe QDs proved to be efficient. Effectiveness of detection was assessed in comparison with CdTe QDs and Acid Yellow 7 (AY7, an effective blood reagent), using two series of depletive blood fingermarks from four donors prepared on four non-porous substrates, i.e. glass, transparent polypropylene, black polyethylene and aluminium foil. The marks were cut in half and processed separately with both reagents, leading to two comparison series (ZnS:Cu vs. CdTe, and ZnS:Cu vs. AY7). ZnS:Cu proved to be better than AY7 and at least as efficient as CdTe on most substrates. Consequently, copper-doped ZnS QDs constitute a valid substitute for cadmium-based QDs to detect blood marks on non-porous substrates and offer a safer alternative for routine use.

Developing an Effective Construction Training Program for Hispanic and American Supervisors and Craft Workers, 2007

Hispanics are a large and growing part of the United States workforce. Projections of the U.S. Census Bureau (2001) state that, by the year 2050, Hispanics will account for 25% of the population. For the Midwest in particular, the Hispanic population is expected to increase 35% by the year 2025. The construction industry is expected to experience a greater percentage increase of its Hispanic population, due to the labor-intensive nature of the industry. This study addresses the expected increase of Hispanic workers in the construction industry by testing the best approaches for delivering training to construction crews with Hispanic workers as well as American supervisors and laborers in the state of Iowa. The research methodology consisted of assessing the effects on communication, safety, work environment, and productivity as a result of the integration training. Results show that integration on-site training decreases workers’ desire to move and increases quality of work and productivity. Most importantly, experimental design was used to show the increasing levels of direct construction communication due to the Toolbox Integration Course for Hispanic Workers and American Supervisors (TICHA) designed as part of this project. This study recommends the creation of a quasi-governmental or association program that can offer continuous research and training that can benefit the construction industry as well as society as a whole. The industry involvement in this process is crucial for contractors. Not only do contractors benefit from reduced insurance premiums when workers act safely, but workers with better communication skills are more productive.

Developing an Effective Construction Training Program for American Supervisors with Hispanic Craft Workers, 2005

In the construction industry, Hispanics have the highest rate of fatal work injuries among the racial/ethnic groups, and productivity in the field is limited by the language barrier between Hispanic workers and their supervisors and the level of education of many Hispanic craft workers. This research developed a training program designed to facilitate the integration process between American supervisors and Hispanic craft workers in a practical and cost-effective way, thus improving productivity and lowering fatality rates. The Iowa State University research team conducted a survey of 38 American supervisors, representing 14 Iowa construction companies. Survey results confirm that communication is the main problem experienced by American supervisors in the job site. Many American supervisors also use or depend on a link-person (an individual who interprets tasks to the rest of the Hispanic crew) to communicate to the Hispanic crew members. Research findings show that language differences affect productivity and workplace safety in the construction industry. Additionally, the educational levels of Hispanic workers indicate that they may not have the literacy skills necessary to understand training materials. This research developed two training courses designed to expand the Spanish communication skills of American supervisors. The research team modified the English-as-a-second-language course developed in Phase I into the Spanish as a Second Language (SSL) Survival Course. A series of technical training courses were also developed, titled Concrete Pavement Construction Basics (CPCB), that cover general practices in concrete pavement construction. They are much shorter and more specialized than the SSL course. The CPCB courses provide American supervisors simple and practical communication tools on a variety of topics to choose from according to their specific needs.

Water Rights and Allocation, January 2010

Iowa Department of Natural Resources commitment to improving the management of both the quantity and quality of water resources, a committee was formed to assess the current policies and practices regarding water rights and allocation, and to make recommendations that would assist the state in moving toward a sustainable future. Water allocation concerns have been raised again in the past few years as increases in the demand for water are projected due to ethanol production, geothermal heating-cooling, and potential irrigation expansion.

Les troubles hyperactifs avec déficit d'attention chez les enfants et les adolescents : rapport sur une étude réalisée à Morges et une enquête auprès du corps médical vaudois.

Cette brochure présente les résultats de l'étude pilote réalisée en 2001 dans le canton de Vaud sur les troubles hyperactifs avec déficit d'attention (THADA). Cette étude concernait plus particulièrement les enfants scolarisés dans les établissements primaires et secondaires de la Ville de Morges. Elle inclut une enquête auprès du corps médical vaudois. [Sommaire] Les troubles hyperactifs avec déficit d'attention (THADA). - L'hyperactivité et ses troubles : une réalité ? : les objectifs de l'étude. - Comment savoir ? : la méthode d'enquête. - Quelles sont les réponses ? : questionnaire de Conners (Conners Rating Scale) ; questionnaire d'Achenbach (Child Behaviour Check List) ; comparaison internationale. - Les facteurs de l'hyperactivité. - Parents, enseignants, enfants : des regards différents. - Diagnostic et traitement médical de l'hyperactivité. - Principales recommandations. Informations pratiques.

Allocation of added selenium in lettuce and its impact on roots

Selostus: Seleenin jakautuminen salaatin versoihin ja vaikutus juuriin

Transportation and Iowa's Economic Future, 1993

This is a study of how transportation policy can be fashioned to improve Iowa's long-term economic prospects. The research focuses on the state level and covers pricing, resource allocation, investment, and other issues that directly affect the performance of public facilities that support transportation of goods and people to and from points in Iowa. Chapter 1 is an introduction. Chapter 2 begins with an assessment of how Iowa's economy is changing, both functionally and spatially. Commuting patterns and methods of goods movement are then discussed. The purpose of this analysis is to provide a context for the exploration of transportation policy issues in subsequent chapters. In Chapter 3 a framework is established for evaluating changes in transportation policies. A working definition of economic development is given and the role of government policies in making an area more attractive to economic activity is considered. Chapter 4 analyzes public policy options for Iowa's roads and highways. These policy options are intended to help the state compete for economic activity. Chapter 5 assesses alternative investment strategies for major navigational facilities on the upper Mississippi River. Chapter 6 examines major transportation policy issues in Iowa's agricultural sector. The current magnitude of agricultural shipments and the roles of several modes are presented. After focusing on issues related to railroad competitiveness, the analysis turns to how Iowa's rural roads should be financed. The need for joint investment and pricing decisions affecting waterways, railroads, and rural roads is stressed. Chapter 7 examines the current status of freight transportation in Iowa. An assessment is made of issues related to trucking and of intermodal transportation and its potential for cost-effective shipping to and from businesses in Iowa. Chapter 8 summarizes the key findings of this study, offering ten recommendations. These recommendations relate to transportation as a means of facilitating economic development.

Effective squark/chargino/neutralino couplings: MadGraph implementation

We have included the effective description of squark interactions with charginos/neutralinos in the MadGraph MSSM model. This effective description includes the effective Yukawa couplings, and another logarithmic term which encodes the supersymmetry-breaking. We have performed an extensive test of our implementation analyzing the results of the partial decay widths of squarks into charginos and neutralinos obtained by using FeynArts/FormCalc programs and the new model file in MadGraph. We present results for the cross-section of top-squark production decaying into charginos and neutralinos.

Rapid LC-MS/MS quantification of the major benzodiazepines and their metabolites on dried blood spots using a simple and cost-effective sample pretreatment.

BACKGROUND: Dried blood spots (DBS) sampling has gained popularity in the bioanalytical community as an alternative to conventional plasma sampling, as it provides numerous benefits in terms of sample collection and logistics. The aim of this work was to show that these advantages can be coupled with a simple and cost-effective sample pretreatment, with subsequent rapid LC-MS/MS analysis for quantitation of 15 benzodiazepines, six metabolites and three Z-drugs. For this purpose, a simplified offline procedure was developed that consisted of letting a 5-µl DBS infuse directly into 100 µl of MeOH, in a conventional LC vial. RESULTS: The parameters related to the DBS pretreatment, such as extraction time or internal standard addition, were investigated and optimized, demonstrating that passive infusion in a regular LC vial was sufficient to quantitatively extract the analytes of interest. The method was validated according to international criteria in the therapeutic concentration ranges of the selected compounds. CONCLUSION: The presented strategy proved to be efficient for the rapid analysis of the selected drugs. Indeed, the offline sample preparation was reduced to a minimum, using a small amount of organic solvent and consumables, without affecting the accuracy of the method. Thus, this approach enables simple and rapid DBS analysis, even when using a non-DBS-dedicated autosampler, while lowering the costs and environmental impact.

Learning in the working place: the educational potential of a multihead microscope in pathology postgraduate training.

Training future pathologists is an important mission of many hospital anatomic pathology departments. Apprenticeship-a process in which learning and teaching tightly intertwine with daily work, is one of the main educational methods in use in postgraduate medical training. However, patient care, including pathological diagnosis, often comes first, diagnostic priorities prevailing over educational ones. Recognition of the unique educational opportunities is a prerequisite for enhancing the postgraduate learning experience. The aim of this paper is to draw attention of senior pathologists with a role as supervisor in postgraduate training on the potential educational value of a multihead microscope, a common setting in pathology departments. After reporting on an informal observation of senior and junior pathologists' meetings around the multihead microscope in our department, we review the literature on current theories of learning to provide support to the high potential educational value of these meetings for postgraduate training in pathology. We also draw from the literature on learner-centered teaching some recommendations to better support learning in this particular context. Finally, we propose clues for further studies and effective instruction during meetings around a multihead microscope.

Efficacité allocative des budgets publics et méthode de l'allocation contingente

Cette contribution s'intéresse à la convergence qui devrait exister entre la demande populaire en matière de prestations publiques et les décisions budgétaires des autorités afin que le secteur public soit efficace du point de vue allocatif. Elle cherche à appliquer la méthode de l'allocation contingente dans une volonté d'impliquer la population dans la répartition des ressources budgétaires. Schématiquement, il s'agit d'interroger les administré-e-s dans le cadre d'une enquête et de leur demander d'allouer un budget donné entre les différentes catégories de prestations publiques que l'administration doit offrir. Cette méthode est appliquée ici de façon expérimentale en utilisant comme périmètre d'analyse les budgets des collectivités locales suisses. Les tests effectués sur les résultats montrent que les préférences révélées ne le sont pas sur une base aléatoire. Si des différences apparaissent entre les allocations contingentes et la manière dont les ressources sont effectivement réparties entre les prestations communales, ces différences semblent découler d'une divergence de vues réelle et non d'un biais lié à la méthode.

Amlodipine and valsartan as components of a rational and effective fixed-dose combination.

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists and blockers of the renin-angiotensin system are widely used today to initiate antihypertensive therapy but, when given as monotherapy, do not suffice in most patients to normalize blood pressure. Combining the two types of agents considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. This is exemplified by the experience accumulated with the recently developed fixed dose combination containing the AT(1)-receptor blocker valsartan (160 mg) and the dihydropyridine amlodipine (5 or 10 mg). In a randomized trial, an 8-week treatment normalized blood pressure (<140/90 mmHg) within 8 weeks in a large fraction of hypertensive patients (78.4% and 85.2% using the 5/160 [n = 371] and 10/160 mg [n = 377] dosage, respectively). Like all AT(1)-receptor blockers valsartan has a placebo-like tolerability. Valsartan prevents to a large extent the occurrence amlodipine-induced peripheral edema. Both amlodipine and valsartan have beneficial effects on cardiovascular morbidity and mortality, as well as protective effects on renal function. The co-administration of these two agents is therefore very attractive, as it enables a rapid and sustained blood pressure control in hypertensive patients. The availability of a fixed-dose combination based on amlodipine and valsartan is expected therefore to facilitate the management of hypertension, to improve long-term adherence with antihypertensive therapy and, ultimately, to have a positive impact on cardiovascular and renal outcomes.