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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.

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.

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.

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.

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.

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 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.

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.

From May 1993 to January 1997, a total of 130 humeral fractures and nonunions were treated using an "elastic" unreamed nail. The elastic nail consists of a cylindrical proximal component tapered for the application of the impactor-extractor, distally containing the proximal ends of four or five secondary nails preloaded to diverge and held together by a retaining system. The surgical approach is through the olecranic fossa apex. Once introduced, the proximal end of the nail locks automatically by diverging the secondary nails in the proximal humeral epiphysis. Distally, the elastic nail is locked with a crossbolt. The elastic nail enables stable fixation of fractures or nonunions and allows early rehabilitation.

Objective: This study was conducted to determine whether the incidence of ectopic pregnancy follows a seasonal rhythm of occurrence. Study Design: A retrospective analysis was performed on 15,639 pregnancies reported in a single department in 5.5 years (January 1992-June 1997). For each pregnancy the time of conception was estimated from medical records. Frequencies of conceptions that terminated in birth, spontaneous abortion, legally induced abortion, and ectopic pregnancy were distributed across the 12-month period. Results: Total pregnancy showed a seasonal rhythm of occurrence, with peak values in March. The rate of ectopic pregnancy showed a rhythm with 2 peaks, in June and December. Nadirs were coincident with the peak and nadir of total conceptions and also with the equinoxes. Spontaneous abortions tended to show a rhythm the inverse of that of ectopic pregnancy. Conclusions: These data show an influence of the seasons on the rate of ectopic pregnancy, which may have implications for both the understanding of ectopic pregnancy's causative mechanisms and its prevention. (Am J Obstet Gynecol 1999;180:1067-71.)

In women, the bone metabolism is markedly influenced by gonadal steroids and by their fluctuations. Indeed, estrogens influence bone metabolism by influencing endocrine and paracrine functions involved in bone remodelling. In normally cycling women, the administration of oral contraceptives does not increase bone mineral density and does not induce deleterious effects on bone. In women with ovulatory disturbances, bone turnover is increased and bone mineral density is lower than in normally cycling women. In these cases, administration of oral contraceptives is capable of blocking increased bone loss and of restoring a normal bone mineral density. Similarly, in women treated with gonadotropin releasing hormone (GnRH) analogs, the concomitant administration of oral contraceptives completely antagonizes GnRH analog-induced bone loss. The progestogenic component of oral contraceptives seems to contribute to the protective effect of estrogens on bone. Oral contraceptives are safe for bone maintenance in normal adult women, and are indeed indicated to prevent postmenopausal osteoporosis in women with ovulatory disturbances.

A new prosthetic, segmented polyether polyurethane portacaval shunt featuring quick-connect anastomotic ends was constructed and evaluated as part of a short-term pharmacokinetic study. The shunts were easily implanted, did not require the use of anticoagulants, and decreased the operative time normally required for this surgical preparation. There was no evidence of thrombosis or venous stasis associated with the shunts.

The biological potency of 15 commercially available tuberculin solutions prepared from a master batch of tuberculin purified protein derivative (PPD) (PPD-CT68) and using a newly formulated diluent (Connaught diluent) containing 0.0005% Tween 80 as an anti-adsorption agent and 0.3% phenol as a preservative, was determined after storage for various intervals at 4, 24 and 37 degrees C. The 5 tuberculin units (TU) per 0.1 ml dose solutions were bioequivalent to a non-stabilized solution of PPD-S whereas the 1 TU and 250 TU per dose solutions were equivalent by calculation to a non-stabilized solution of PPD-S. It was found that the PPD solutions of all 3 strengths, 1, 5 and 250 TU per dose, were stable for at least 3 years at 4 degrees C and for 2 years at room temperature (24 degrees C). Even at 37 degrees C the solutions of all 3 strengths were stable for at least 1 year. The stability of Connaught tuberculin PPD solutions has not been affected by the changes in formulation. The stability data suggest that the expiry date of the newly formulated tuberculin products could be at least two years from the data of the last satisfactory potency test. Although these products are stable for at least 1 year even at 37 degrees C, we nonetheless agree with the Canadian and U.S. regulations that they be stored at 2 to 8 degrees C in their original containers.

During the storage of nonstabilized, dilute solutions of tuberculin (solutions containing no antiadsorption agent) in glass containers and glass or plastic syringes, great losses of tuberculin occur due to the adsorption of tuberculoprotein to the wall of these containers. Using glass vials filled with tuberculin purified protein derivative-14C at the concentration of 5 tuberculin units per dose, the concentration of the nonstabilized tuberculin solution decreased to 60 per cent of its original concentration one day after filling. During withdrawal in disposable syringes with a capacity of adsorption ranging from 0.19 µg to 0.23 µg purified protein derivative per cm2, the concentration of tuberculin decreased further to approximately 50 per cent when it was immediately injected and to approximately 40 per cent, 30 per cent, 20 per cent, and 10 per cent of the original concentration when it was injected after 20 minutes, 1 hour, 4 hours, and 8 hours, respectively. After 24 hours in the disposable syringe, ...

The biological reactivity of two commercially available tuberculin preparations was measured in 168 subjects (9 with active tuberculosis; 98 with inactive tuberculosis; and 61 general population). One tuberculin had 5 tuberculin units (TU) per 0-1 ml dose relative to a stabilized solution of PPD-S, whereas the other preparation was bioequivalent to 5 TU per 0-1 ml dose of unstabilized PPD-S, and was therefore of lower potency. Differences between the tuberculins were more evident when an induration of larger than or equal to 10 mm was considered as positive. Using a criterion of larger than or equal to 5 mm the differences were smaller, but the frequency of non-tuberculous responders was increased using this criterion. The average difference between the tuberculins was of the order of 5 mm regardless of the criterion of postivity. The use of chemoprophylaxis based on reaction size necessitates that the physician should know which of these two commercially available tuberculins is being used.

Preliminary studies of some of the properties of stearyl tyrosine have shown that it is non-toxic, free of adverse reactions at the sites of injection, non-pyrogenic, stable upon storage and easy to sterilize. Formalin inactivated poliovirus vaccine (IPV) adjuvanted with stearyl tyrosine hydrochloride induced significantly higher titres of antibodies in non-human primates, after two injections, than the non-adjuvanted vaccine. Furthermore, the adjuvanted vaccine, even when diluted 1:4, showed consistently higher antibody titres as well as a longer persistence of antibodies than the non-adjuvanted undiluted vaccine. These studies suggest that stearyl tyrosine is an excellent and cost effective adjuvant for IPV. Hence further investigation with this novel synthetic compound would be worthwhile to ascertain its adjuvanticity for IPV in human subjects.