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The optical diffuse reflectance data of a semiconductor material is usually converted into the Kubelka–Munk function before proceeding to process the conventional Tauc’s plot from which optical bandgap energy can be determined. Firstly, it is conventional/ customary to convert the percentage reflectance (R∞(%)) data which is obtained from UV-vis measurement into an equivalent reflectance (R∞) that range between 0 and 1 before processing the Tauc’s plot. Secondly, the Kubelka–Munk function is usually multiplied by the incident photon energy, hv, to produce an all-elements/ comprehensive Tauc’s plot. Literature is scarce to convincingly demonstrate that a correct bandgap value can also be obtained from the Tauc’s plot that is derived directly from the (R∞(%)) data without having to convert to R∞. Also, publication is rarely available to demonstrate that a correct bandgap value can be determined without having to multiply the Kubelka–Munk function by hv. Investigation shows diminutive differences in the bandgap values estimated from the R∞(%)-based Tauc’s plots and the equivalent R∞-based Tauc’s plots. This suggests that either of the methods can be employed for a proper bandgap estimate. Additionally, a comparison between the magnitude of the bandgap energies determined from the comprehensive Tauc’s plot and when the Kubelka–Munk function is not multiplied by \(hv\) shows insignificant differences in the estimated values. This suggests that either of the two methods can be used to obtain a reliable bandgap for direct and indirect optical gap semiconductors.

Crosscutting concerns are an intrinsic problem of legacy systems, hindering their maintenance and evolution. A possible solution is to modernize these systems employing aspect-orientation, which provides suitable abstractions for modularizing these kind of concerns. Architecture-Driven Modernization is a more specific kind of software reengineering focused on employing standard metamodels along the whole process, promoting interoperability and reusability across different tools/vendors. Its main metamodel is the Knowledge Discovery Metamodel (KDM), which is able to represent a significant amount of system details. However, up to this moment, there is no extension of this metamodel for aspect-orientation, preventing software engineers from conducting Aspect-Oriented Modernizations. Therefore, in this paper we present our experience on creating a heavyweight and a lightweight extension of KDM for aspect-orientation. We conducted two evaluations. The first one showed all aspect-oriented concepts were represented in both extensions. The second one was a experiment, in which we have analyzed the productivity of software engineers using both extensions. The results showed that the heavyweight extension propitiate a more productive environment in terms of time and number of errors when compared to the lightweight one.

Many of us in the animal research community regularly face an internal conflict. We witness developments of new treatments while recognizing that animals experience study-based harms despite our systems of care. Beauchamp and DeGrazia identify significant gaps left by reigning models of harm–benefit principles and the Three Rs. Their six principles must be seriously considered in debates about the conditions of morally justified animal research because they provoke bioethical questions neglected by harm–benefit analyses (HBA) and the Three Rs. However, some problems need more discussion than can be found in Beauchamp and DeGrazia’s framework. For example, more material on basic research and its justification would be helpful, as would analysis of how improvements in study design are paramount for increasing the benefit of HBA.

Context: The modernization of a legacy software system is a reality of companies that need to improve their systems. Architecture-Driven Modernization (ADM) is a model-driven blueprint that support modernization engineers in the modernization processes. ADM considers the usage of reengineering and model driven architecture (MDA) concepts and advocates the employment of standard metamodels, such as Knowledge Discovery Metamodel (KDM). One of the main challenges while considering ADM is on how modernization tools (MTs) should be developed in order to allow the success of modernization projects that follows the ADM blueprint. Objective: In this paper we address the main requirements and guidelines on how modernization tools should be designed by means of a Reference Architecture (RA) for ADM-based Modernization Tools named RADMoTo. Methodology: We followed a four-steps methodological process to build RADMoTo and to evaluate it we submitted the RA technical report and a survey to ADM experts and software architects in order to get a feedback of the RA acceptance level. Results: As a result, we found out that, in general, the participants believe that our RA provides an acceptable level while considering the architectural views. Conclusion: The feedback from the participants helped in the improvement process of the RA. Thus, we claim that this paper provides concrete guidelines on how modernization tools should be designed and on how architectural instances derived from our RA could benefit from reusability and interoperability.

There is no prescribed stage or standardized point at which an animal model protocol is reviewed for reproducibility and translatability. The method of review for a reproducible and translatable study is not consistently documented in peer literature, and this is a major challenge for those working with animal models of human diseases. If the study is ill designed, it is impossible to perform an accurate harm/benefit analysis. In addition, there may be an ethical challenge if the work is not reproducible and translatable. Animal welfare regulations and other documents of control clearly state the role of the Institutional Animal Care and Use Committees are to look at science justification within the context of animal welfare. This article, concentrating on models not governed by regulations, outlines issues and offers recommendations for refining animal model review with a goal to improve study reproducibility and translatability.

Purpose Cardiomyocytes progenitor cells (CMPCs) are a candidate cell source for cardiac regenerative therapy. To assess their full potential for cardiac regeneration, it is essential to know if and how CMPCs sense and respond to the three-dimensional (3D) environment and the mechanical stimuli provided by the beating heart. Therefore, we study the response to cyclic strain of undifferentiated and predifferentiated human CMPCs in a 2D environment, as well as CMPC responses to unidirectionally constrained versus stress-free (unconstrained) 3D environments. The latter responses were studied using a hydrogel system that allows for interaction of the cells with a simulated ‘host’ tissue. Methods To test mechanosensitivity of CMPCs in 2D and 3D environments, the response of L9TB CMPCs to uniaxial (cyclic) strain (10% with 0.5 Hz) was investigated. To represent the 3D environment, CMPCs were cultured in unidirectionally constrained and stress-free collagen/Matrigel hydrogels, where the constrainment provides a static strain to the cells. The cellular mechanoresponse to the applied (cyclic) strain was quantified by cellular re-orientation away from the strain direction (strain avoidance). Next to cellular re-orientation, the effect of strain on cell differentiation was analyzed. Results Our results indicate that while undifferentiated cells maintain their original orientation, upon early cardiomyogenic differentiation (predifferentiated) CMPCs exhibit a distinct strain avoidance response during 48hrs of cyclic straining in a 2D environment. In 3D unidirectionally constrained hydrogels, undifferentiated CMPCs retain their cardiomyogenic profile. CMPCs cultured in 3D collagen/Matrigel hydrogels respond to static mechanical strains as expected by cell alignment. Conclusions Our results suggest that CMPCs respond to the presence of mechanical stimuli, in this research mimicked by the application of uniaxial (cyclic) strain in 2D and 3D environments, suggesting that CMPCs are indeed mechanosensitive. Although in 2D environments, mechanosensitivity of the CMPCs is dependent on their differentiation status. Our findings provide the first understanding of the ability of human CMPCs to sense mechanical stimuli, which is the first initial step in mechanotransduction. Mechanotransduction is essential for optimal recruitment, migration, and mechanical integration of progenitor cells into the injured myocardium. Therefore, the presented results can contribute to enhance efficacy of current treatments of cardiac disease, as well as to develop novel endogenous regeneration strategies.

Photocatalytic, superhydrophobic and self-cleaning capabilities were promoted on AC 6 and AC 14 asphalt mixtures by spraying of TiO2 and/or ZnO. Initially, physicochemical and morphological properties of bitumen samples were evaluated by Fourier Transform Infrared Spectroscopy and Atomic Force Microscopy after the solution spraying of TiO2, ZnO and TiO2 ZnO. Then, to assure those capacities, Water Angle Contact and Photocatalytic Efficiency tests were carried out on both mixtures. Finally, mixtures were assessed mechanically through Indirect Tensile Strength. Photocatalytic, superhydrophobic and self-cleaning properties were guaranteed for AC 14 with TiO2 and TiO2 ZnO and AC 6 with TiO2 ZnO without deteriorations., This work was partially financed by FCT—Fundação para a Ciência e Tecnologia—under the project PTDC/FIS/120412/2010: ‘‘Nanobased concepts for Innovative & Eco-sustainable constructive material’s surfaces’’ and project PEst-OE/ECI/UI4047/2014 supported by Portuguese Foundation for Science and Technology., info:eu-repo/semantics/publishedVersion

Architecture-Driven Modernization (ADM) is an initiative of the Object Management Group (OMG) whose main purpose is to provide standard metamodels for software modernization activities. The most important metamodel is the Knowledge Discovery Metamodel (KDM), which represents software artifacts in a language-agnostic fashion. A fundamental step in software modernization is refactoring. However, there is a lack of tools that address how refactoring can be applied in conjunction with ADM. We developed a tool, called KDM-RE, that supports refactorings in KDM instances through: (i) a set of wizards that aid the software modernization engineer during refactoring activities; (ii) a change propagation module that keeps the internal metamodels synchronized; and (iii) the selection and application of refactorings available in its repository. This paper evaluates the application of refactorings to KDM instances in an experiment involving seven systems implemented in Java. We compared the pre-refactoring versions of these systems with the refactored ones using the Quality Model for Object-Oriented Design (QMOOD) metric set. The results from this evaluation suggest that KDM-RE provides advantages to software modernization engineers refactoring systems represented as KDMs.

The structural properties and relaxation processes of magnetization in [Ni 81 Fe 19 ( t 1 )/Ru( t 2 )] N superlattices ( N =number of bilayers) were analyzed by ferromagnetic resonance (FMR) with a fixed microwave frequency. One series of samples was deposited with constant NiFe layer thickness ( t 1 ) and variable Ru layer thickness ( t 2 ); the other series, with constant t 2 and variable t 1 . A single FMR mode was observed for t 2 t 1 >75 A and it has been attributed to the resonance of the exchange-coupled NiFe layers across the Ru interlayers. For the other values of t 1 and t 2 , several FMR modes appeared and they were associated to non-coupled magnetic phases with different effective magnetization formed during the multilayer growth. The FMR linewidths were analyzed as a function of the magnetic layer thickness and a strong dependence on t 1 −2 was observed. It was attributed to the contribution of the two-magnon scattering mechanism for the linewidth.

Adaptive Systems (ASs) can adapt themselves to achanging environment or new user needs. Monitors are essential in AS, being responsible for collecting and processing data from environment. There exist different kinds of monitors with distinct characteristics. Based on a literature review, we have noticed that Monitors are usually designed and implemented in an inadequate way: i) making them obscure in the source-code, ii) compelling all of them to have the same polling rate and also iii) predetermining the execution order among them. This leads to maintenance, evolution and performance problems. Besides, based on our observations, this erroneous way monitors are implemented follows a pattern and it is a recurrent practice. Therefore, we believe it can be classified asMonitor Smells of Adaptive Systems. In this paper we present two architectural smells we have identified: the Obscure Monitor and the Oppressed Monitors. The first smell occurs when the monitors are not evident in the source-code. The second smell occurs when monitors are compelled to have the same poling rate and an immutable execution order at runtime. The presence of these smells compromises the reusability, evolvability and maintainability. We have also conducted an exploratory study by comparing the impact of maintenance tasks in the original version of an AS called PhoneAdapter with a refactored version, in which the smells were removed. The results indicate the maintenance is facilitated in the version without the smells.

Members of the research community aim to both produce high-quality research and ensure that harm is minimized in animals. The primary means of ensuring these goals are both met is the 3Rs framework of replacement, reduction, and refinement. However, some approaches to the 3Rs may result in a ‘check box mentality’ in which IACUC members, researchers, administrators, and caretakers check off a list of tasks to evaluate a protocol. We provide reasons for thinking that the 3Rs approach could be enhanced with more explicit discussion of the ethical assumptions used to arrive at an approved research protocol during IACUC review. Here we suggest that the notion of moral considerability, and all of the related issues it gives rise to, should be incorporated into IACUC discussions of 3Rs deliberations during protocol review to ensure that animal wellbeing is enhanced within the constraints of scientific investigation.

IntroductionWellness self-management is an adaptation and expansion of the illness management and recovery, an internationally recognized best practice. WSM is a recovery-oriented, curriculum-based practice designed to help adults with severe mental health problems make decisions and take action to manage symptoms and improve their quality of life.ObjectivesIn the present study, the Italian translation of the WSM was implemented and validated. Moreover, the impact of its application in a day hospital setting on cognitive functions, psychopathology, personal resources and real-life functioning with respect to treatment as usual (TAU) was investigated.AimsThe study was aimed at assessing the effectiveness of a semi-structured version of WSM in a day hospital setting in patients with severe mental illness.MethodsFourteen patients with a diagnosis of severe mental illness were recruited and randomly assigned to either WSM or TAU. WSM participants attended four 2-hour sessions per week for 1 month, including lessons selected on the basis of the goals of participants. Both groups received weekly planned treatment in the day-hospital setting and continued their pharmacotherapy.ResultsThe two groups of patients were comparable for age, education, cognitive functioning and psychopathological severity. WSM produced a significantly greater improvement in neurocognition, psychopathology, personal resources and real-life functioning with respect to TAU.ConclusionsOur results offer promising preliminary evidence that the use of WSM provides an effective complement to current mental health treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of crosssectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship. © The Author 2014. Published by Oxford University Press. All rights reserved.

A surface characterization technique based on the Internal Second-Harmonic Generation (SHG) in optoelectronic devices has been used to study the mirror degradation of 1.55 μm semiconductor optical amplifiers (SOAs) exposed to an antireflection coating deposition technique and 980 nm pump lasers suffering from mirror oxidation during life-tests. In both cases, an overall increase in SH emission was observed, as a consequence of mechanical stress enhancement and defects formation due to oxidation phenomena occurring at the interface between semiconductor and coating film. In the case of pump lasers, an oscillating, periodic trend superimposed to the general increasing one was also observed and interpreted as the periodic relaxation of compressive strain in the active layer due to vacancies formation in the near-mirror semiconductor layer.

Forensic laboratories can be called to examine illicit Cannabis samples (marijuana) to identify their geographical origin. They can also be required to compare different seizures to establish whether they were drawn from the same original lot. The quantitative determination of selected organic components is one of the criteria currently used in such investigations. This study aimed at evaluating the inorganic element pattern of marijuana as a possible additional diagnostic tool. Four commercial cultivars of Cannabis sativa L. were grown in field experiments planned so that edaphic and climatic growth conditions varied slightly among the fields. The experimental design produced six populations. Population variability for the elements sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), copper (Cu), manganese (Mn), iron (Fe), zinc (Zn), and molybdenum (Mo) accumulation in leaves (L) and inflorescences (FL) of female plants was determined. For each element, the analytical data for the L and FL ...

One of the research areas of modern medicine is to work on the identification of biological markers, such as biomolecular ones, for neoplastic diseases from occupational origin. MiRNA, short RNA no-codifing sequences, are recently identified such as diagnostic markers in several type of cancer. For this reason, the aim of our study is to analyze the possible role of miRNA in malignant pleural mesothelioma, a rare and aggressive tumor with a strong resistance to conventional therapies and poor prognosis. Total RNA, containing also miRNA, was extracted, and RNA was retro-transcripted with specific primers. Then, miRNA expression was tested using real-time PCR method and particular probes for each miRNA. The RNU6B was used such as housekeeping gene, for data normalization. This work represents the first step for the identification of a specific miRNA pattern for MPM, which will be useful in the diagnosis of MPM and for a personalized therapeutic treatment.

Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS).Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P0.001) and number of suture knots (P0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related.The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

The electron velocity distribution function in the solar wind has often been described as the superposition of an isotropic core, a moderately energetic and slightly anisotropic halo and a high energy field aligned beam. The relative weight of these components depends on the characteristics of the solar wind streams (fast and slow) and on the heliocentric distance. We present kinetic simulations using the model given in [1] to study the effects of electron‐electron and electron‐proton collisions on the electron velocity distribution function in the interplanetary space beyond ∼0.3 AU from the Sun. We show that collisions do naturally generate a two population electron velocity distribution with an isotropic and cold “core” and a hot and collimated “halo.” The temperature profiles and temperature anisotropies observed in our simulations are consistent with spacecraft observations [2, 3, 4]. Since waves are not included in our simulations we suggest that Coulomb collisions are an essential ingredient which should be included in any model of the evolution of the electron velocity distribution function in interplanetary space.

We have studied field-and current-driven domain-wall (DW) creep motion in a perpendicularly magnetized Co/Pt multilayer wire by real-time Kerr microscopy. The application of a dc current of density of less than or similar to 10(7) A/cm(2) assisted only the DW creeping under field in the same direction as the electron flow, a signature of spin-transfer torque effects. We develop a model dealing with both bidirectional spin-transfer effects and Joule heating, with the same dynamical exponent mu = 1/4 for both field-and current-driven creep, and use it to quantify the spin-transfer efficiency as 3.6 +/- 0.6 Oe cm(2)/MA in our wires, confirming the significant nonadiabatic contribution to the spin torque.

Endometriosis is the presence of endometrial tissue, including endometrial glands and stroma, outside the uterine cavity. The incidence of endometriosis in the general population is almost unknown, because it varies between 1% and 50%, depending on the paper considered. In any case, the incidence of bladder endometriosis is generally considered about 1% or less of endometriotic patients. The aim of this study is to evaluate the effectiveness of preoperative exams and the effectiveness of laparoscopic treatment.We enrolled 21 patients operated laparoscopically for a severe stage of endometriosis, including at least a bladder localization of 10 mL; in 60% of cases a bowel surgery was associated in the cause of a digestive endometriosis. A complete preoperative and follow-up evaluation was carried out for all patients.The preoperative investigation, especially abdominal sonography, predicted endometriotic bladder invasion in only 38% of cases. Urinary symptomatology was present in only 61.9% of cases. The postoperative follow-up showed the remarkable effectiveness of laparoscopic treatment for the cancellation of pain and to improve the quality of life for patients.Finally, the treatment of severe endometriosis is possible and effective by laparoscopy even in the cases where there is a bladder localization and when, in the absence of specific symptomatology, it isn't diagnosed preoperatively.

The research was carried out during 1999 in 8 different localities in Northern Italy. The nematodes were extracted from soil samples of rhizosphere of corn plants (Zea mays L.). The objective of the study was to investigate plant-parasite nematodes associated with maize. Some phytophagous genera are common pests of this crop and its yield-loss are often due to their high densities. In addition the nematode community was investigated for the genus composition, the trophic structure and its biodiversity. After the extraction from soil with a Bearmann funnel and Ludox centrifugation, nematodes were identified at genus level. They belonged to 22 families and 45 different genera. The genus Rhabditis, Pratylenchus, Helicotylenchus and Acrobeloides made up more than 70% of the total nematodes collected. The dominant trophic group was the bacterial feeders (61%) in particular Rhabditis, that was the most abundant and often the dominant one. Phytophagous represented in almost all fields more than 30% of the total nematodes. In all the examined sites biodiversity was quite low, being the H' values no more than 1.08. The data indicates a high level of disturbance. In some localities high densities of Helicotylenchus and Pratylenchus were found. While these nematodes have been identified as being potentially harmful for corn plants in our latitudes, especially in light soils, this research could give an indication for further monitoring studies regarding plant parasitic nematodes of corn crops. This data is particularly important considering that methyl bromide, often used in Italian agriculture against soil pathogens, has been banned since the beginning of 2005.

Few data is available on the nematodes found in Brassicaceae, except for the most important plant parasite. However, studying the structure of nematofauna could be an important database for the soil quality and in order to assess the effects of future disturbance. This is particularly important considering that the diffusion of the canola crop in the world is increasing because of its use as a bio-diesel. Very diffused is also the Bt variety of oil seed rape, and, in this case, the study of the impact on the soil health and on bio-diversity is essential. In this research we have analyzed the nematode community, used as a bio-indicator of the soil condition. The nematofauna found in canola (Brassica napus var. oleifera) fields located in Southern Italy (Metaponto - MT) was investigated. The nematode community was studied considering its abundance, genus composition and trophic structure. Maturity and biodiversity indices were also calculated. A total of 5286 nematodes were extracted. They belong to 14 families and 24 genera. Bacterial and fungal feeders, 50.18% and 42.90% of the total respectively, dominated the trophic structure. Aphelencus is the most abundant genus (23.71%) followed by Acrobeloides (20.49%) and Aphelencoides (19.18%). Among plant feeders (6.59%), Pratylenchus is the dominant genus (2.20%) and Tylenchidae the main family (3.54%). No infestation of Meloidogyne, Heterodera or Naboccus, important plant-parasitic nematodes of canola crops, was recorded. Other important phytophagous were Helycotylenchus (0.5%), Trichotylenchus (0.5%) and Filenchus (0.9%). All of them had an abundance level below injury level. The indices of biodiversity are rather low (H'=0.93, J'=0.67), as is typical for agro ecosystems. However, the nematofauna community is quite well structured (N2=6.31, D=0.16) and the maturity index rather high (EMI=1.94). These values demonstrate that oilseed rape has a lower impact on the soil compared to other crop systems and that it could be taken into consideration for crop rotation programs. Canola could follow other more stressful crops, trying to maintain soil equilibrium.

The use of animals in biomedical research is a privilege granted by society, and the rules and regulations that govern this usage are in place to ensure the welfare of the laboratory animal subjects. The IACUC is the institutional commitment to this protection, and IACUC members continually challenge themselves and others to find a balance between achieving both scientific and animal welfare objectives. This is accomplished by incorporating the three Rs (reduction replacement and refinement) into animal usage in research, teaching and testing. IACUC members can be advocates for both the animals and the scientist. A good working relationship between the committee and the attending and/or laboratory animal veterinarian will promote identification, interpretation and clarification of the major rules and regulations. It is ultimately the responsibility of each investigator to comply with regulations for the welfare and safety of the animals and people involved in any research project. Animal models used in inflammation research often have specific considerations that need to be addressed to minimize issues of pain and distress. This includes the use of well-defined endpoints, the proper use of pharmacological interventions and the use of other pain-alleviating methods.

Insulin-like growth factor I (IGF-1) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-1 is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-1 carriers may predict circulating levels of IGF-1 and have an impact on cancer risk. We tested this hypothesis with a case - control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-1 and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 50 end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 50 end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.

Objective: To evaluate the central effect exerted by different progestins used for hormone replacement therapy. Methods:Randomised, placebo-controlled study. One hundred-twenty postmenopausal women on continuous hormonal replacement therapy with transdermal estradiol (50g per day) associated, for 10 days every 28 days, with four different progestins: dydrogesterone (DYD; 10 mg per day; n = 20), medroxyprogesterone acetete (MPA; 10 mg per day; n = 20), nomegestrol acetate (NMG; 5 mg per day; n = 20) or norethisterone acetate (NETA; 10 mg per day; n = 20). Other 40 women, 10 for each treatment group, were used as controls and were monitored for a single cycle of 28 days during the administration of transdermal estradiol plus placebo. Morning basal body temperature (BBT) was monitored for 28 days. Anxiety, by the state-trait anxiety inventory, and depression, by the self-evaluation depression scale of Zung, were evaluated just prior to and in the last 2 days of the 10-day progestins adjunct. Results: All progestins except DYD increased ( P< 0.0001) BBT by 0.3–0.5 ◦ C. Anxiety was decreased by DYD (−2.3 + 1.1; P< 0.01) and MPA (−1.5 + 0.5; P< 0.01), but not by NMG or NETA. Depression did not significantly increase during progestins and actually decreased during MPA (−3.0 + 0.7; P< 0.01). Only the effect of DYD on anxiety and that of MPA on depression were significant versus the control group ( P< 0.05). Conclusions: Different progestins exert different central effects. DYD has the peculiarity of not increasing BBT and of decreasing anxiety, which is also decreased by MPA. Depression is not negatively affected by the tested progestins and it may be ameliorated by MPA. The present data may help to individualise the progestin choice of hormone replacement therapy. © 2003 Elsevier Ireland Ltd. All rights reserved.

Best practices result from a partnership between law, science, and the people working with the animals on regulated studies. In an ideal setting, people working with animals observe and study animal behavior as influenced by different housing and handling paradigms. These observations are published to create a body of science, and laws are promulgated based on the science. The ideal world does not exist, but there are certain components of best practices common to all species. These components include study design, housing, social contact, diet/feed, enrichment devices, and human interaction. This paper outlines how the forces of law, science, and people work to create best practices for species in regulated studies, specifically mice, rats, rabbits, dogs, and nonhuman primates.