Closed and open grade I and II tibial shaft fractures treated by reamed intramedullary nailing.

OBJECTIVE: To evaluate the results of closed and open grade I and II tibial shaft fractures treated by reamed nail and unreamed nailing. SUBJECTS AND METHODS: Between 1997 and 2000, 119 patients with tibial shaft fractures were treated with reamed tibial nails. Postoperatively 96 patients (70 closed and 26 grade I and II open fractures) were followed clinically and radiologically for up to 18 months. The nail was inserted either by patellar tendon splitting or by nonsplitting technique. The nail was inserted after overreaming by 1.5 mm. Postoperatively, patients with isolated tibial fracture were mobilized by permitting partial weight bearing on the injured leg for 6 weeks. Patients with associated ankle fractures were allowed to walk with a Sarmiento cast. RESULTS: Postoperatively, 6 (6.3%) patients developed a compartment syndrome after surgery. In 48 (50%) cases, dynamization of the nail was carried out after a mean period of 12 weeks for delayed union. Overall, a 90.6% union was obtained at a mean of 24 weeks without difference between closed or open fractures. Two (2.1%) patients with an open grade II fracture developed a deep infection requiring treatment. A 9.4% rate of malunion was observed. Eight (8.3%) patients developed screw failure without clinical consequences. At the last follow-up, 52% of patients with patellar tendon splitting had anterior knee pain, compared to those (14%) who did not have tendon splitting. CONCLUSION: Reamed intramedullary nail is a suitable implant in treating closed as well as grade I and II open tibial shaft fractures.

The natural history of type II odontoid fractures in the elderly population. A retrospective study over a 14 years period.

Odontoid fractures are the most common cervical fractures in the adult population. They represent 9 to 18 % of all cervical fractures and the type II is the most common. The incidence of neurologic deficits (ND) in odontoid fractures varies between 3 to 25%. A recent study showed that patients with ND had a mortality rate increased by 4.72 times and a complication rate higher of 1.18 times. The most common complication in patients with ND was respiratory distress8. Surprisingly, although type II odontoid fractures are frequent cervical fractures, their natural history has been poorly described. Surgery for odontoid fractures is well described. However, there are so far guidelines based on class II and class III evidence only regarding indications for surgery and regarding surgical techniques. The class II guidelines recommend to consider surgical stabilization and fusion for type II odontoid in patients over 50 years of age. The class III recommendations are to first manage non-displaced odontoid type II fracture with external immobilization and that translation of 5mm or more is associated with a high rate of non- union with the conservative treatment and should be treated surgically.

Ecologie industrielle de l'aluminium, flux de matières et d'énergie : réalités et enjeux du recyclage

Dans les dernières années du 20ème siècle, l'aluminium a fait l'objet de beaucoup de communications outrancières et divergentes cautionnées par des scientifiques et des organismes faisant autorité. En 1986, la société PECHINEY le décrète perpétuel tel le mouvement « L'aluminium est éternel. Il est recyclable indéfiniment sans que ses propriétés soient altérées », ce qui nous avait alors irrité. Peu de temps après, en 1990, une communication tout aussi outrancière et irritante d'une grande organisation environnementale, le World Wild Fund, décrète que « le recyclage de l'aluminium est la pire menace pour l'environnement. Il doit être abandonné ». C'est ensuite à partir de la fin des années 1990, l'explosion des publications relatives au développement durable, le bien mal nommé. Au développement, synonyme de croissance obligatoire, nous préférons société ou organisation humaine et à durable, mauvaise traduction de l'anglais « sustainable », nous préférons supportable : idéalement, nous aurions souhaité parler de société durable, mais, pour être compris de tous, nous nous sommes limités à parler dorénavant de développement supportable. Pour l'essentiel, ces publications reconnaissent les très graves défauts de la métallurgie extractive de l'aluminium à partir du minerai et aussi les mérites extraordinaires du recyclage de l'aluminium puisqu'il représente moins de 10% de la consommation d'énergie de la métallurgie extractive à partir du minerai (on verra que c'est aussi moins de 10% de la pollution et du capital). C'est précisément sur le recyclage que se fondent les campagnes de promotion de l'emballage boisson, en Suisse en particulier. Cependant, les données concernant le recyclage de l'aluminium publiées par l'industrie de l'aluminium reflètent seulement en partie ces mérites. Dans les années 1970, les taux de croissance de la production recyclée sont devenus plus élevés que ceux de la production électrolytique. Par contre, les taux de recyclage, établis à indicateur identique, sont unanimement tous médiocres comparativement à d'autres matériaux tels le cuivre et le fer. Composante de l'industrie de l'aluminium, le recyclage bénéficie d'une image favorable auprès du grand public, démontrant le succès des campagnes de communication. A l'inverse, à l'intérieur de l'industrie de l'aluminium, c'est une image dévalorisée. Les opinions émises par tous les acteurs, commerçants, techniciens, dirigeants, encore recueillies pendant ce travail, sont les suivantes : métier de chiffonnier, métier misérable, métier peu technique mais très difficile (un recycleur 15 d'aluminium n'a-t-il pas dit que son métier était un métier d'homme alors que celui du recycleur de cuivre était un jeu d'enfant). A notre avis ces opinions appartiennent à un passé révolu qu'elles retraduisent cependant fidèlement car le recyclage est aujourd'hui reconnu comme une contribution majeure au développement supportable de l'aluminium. C'est bien pour cette raison que, en 2000, l'industrie de l'aluminium mondiale a décidé d'abandonner le qualificatif « secondaire » jusque là utilisé pour désigner le métal recyclé. C'est en raison de toutes ces données discordantes et parfois contradictoires qu'a débuté ce travail encouragé par de nombreuses personnalités. Notre engagement a été incontestablement facilité par notre connaissance des savoirs indispensables (métallurgie, économie, statistiques) et surtout notre expérience acquise au cours d'une vie professionnelle menée à l'échelle mondiale dans (recherche et développement, production), pour (recherche, développement, marketing, stratégie) et autour (marketing, stratégie de produits connexes, les ferro-alliages, et concurrents, le fer) de l'industrie de l'aluminium. Notre objectif est de faire la vérité sur le recyclage de l'aluminium, un matériau qui a très largement contribué à faire le 20ème siècle, grâce à une revue critique embrassant tous les aspects de cette activité méconnue ; ainsi il n'y a pas d'histoire du recyclage de l'aluminium alors qu'il est plus que centenaire. Plus qu'une simple compilation, cette revue critique a été conduite comme une enquête scientifique, technique, économique, historique, socio-écologique faisant ressortir les faits principaux ayant marqué l'évolution du recyclage de l'aluminium. Elle conclut sur l'état réel du recyclage, qui se révèle globalement satisfaisant avec ses forces et ses faiblesses, et au-delà du recyclage sur l'adéquation de l'aluminium au développement supportable, adéquation largement insuffisante. C'est pourquoi, elle suggère les thèmes d'études intéressant tous ceux scientifiques, techniciens, historiens, économistes, juristes concernés par une industrie très représentative de notre monde en devenir, un monde où la place de l'aluminium dépendra de son aptitude à satisfaire les critères du développement supportable. ABSTRACT Owing to recycling, the aluminium industry's global energetic and environmental prints are much lower than its ore extractive metallurgy's ones. Likewise, recycling will allow the complete use of the expected avalanche of old scraps, consequently to the dramatic explosion of aluminium consumption since the 50's. The recycling state is characterized by: i) raw materials split in two groups :one, the new scrap, internal and prompt, proportional to semi-finished and finished products quantities, exhibits a fairly good and regular quality. The other, the old scrap, proportional to the finished products arrivïng at their end-of--life, about 22 years later on an average, exhibits a variable quality depending on the collect mode. ii) a poor recycling rate, near by that of steel. The aluminium industry generates too much new internal scrap and doesn't collect all the availa~e old scrap. About 50% of it is not recycled (when steel is recycling about 70% of the old scrap flow). iii) recycling techniques, all based on melting, are well handled in spite of aluminium atiiníty to oxygen and the practical impossibility to purify aluminium from any impurity. Sorting and first collect are critical issues before melting. iv) products and markets of recycled aluminium :New scraps have still been recycled in the production lines from where there are coming (closed loop). Old scraps, mainly those mixed, have been first recycled in different production lines (open loop) :steel deoxidation products followed during the 30's, with the development of the foundry alloys, by foundry pieces of which the main market is the automotive industry. During the 80's, the commercial development of the beverage can in North America has permitted the first old scrap recycling closed loop which is developing. v) an economy with low and erratic margins because the electrolytic aluminium quotation fixes scrap purchasing price and recycled aluminium selling price. vi) an industrial organisation historically based on the scrap group and the loop mode. New scrap is recycled either by the transformation industry itself or by the recycling industry, the remelter, old scrap by the refiner, the other component of the recycling industry. The big companies, the "majors" are often involved in the closed loop recycling and very seldom in the open loop one. To-day, aluminium industry's global energetic and environmental prints are too unbeara~ e and the sustainaЫe development criteria are not fully met. Critical issues for the aluminium industry are to better produce, to better consume and to better recycle in order to become a real sustainaЫe development industry. Specific issues to recycling are a very efficient recycling industry, a "sustainaЫe development" economy, a complete old scrap collect favouring the closed loop. Also, indirectly connected to the recycling, are a very efficient transformation industry generating much less new scrap and a finished products industry delivering only products fulfilling sustainaЫe development criteria.

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials.

BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. II: Confirmatory analysis.

For doping control, analyses of samples are generally achieved in two steps: a rapid screening and, in the case of a positive result, a confirmatory analysis. A two-step methodology based on ultra-high-pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was developed to screen and confirm 103 doping agents from various classes (e.g., beta-blockers, stimulants, diuretics, and narcotics). The screening method was presented in a previous article as part I (i.e., Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. Part I: screening analysis). For the confirmatory method, basic, neutral and acidic compounds were extracted by a dedicated solid-phase extraction (SPE) in a 96-well plate format and detected by MS in the tandem mode to obtain precursor and characteristic product ions. The mass accuracy and the elemental composition of precursor and product ions were used for compound identification. After validation including matrix effect determination, the method was considered reliable to confirm suspect results without ambiguity according to the positivity criteria established by the World Anti-Doping Agency (WADA). Moreover, an isocratic method was developed to separate ephedrine from its isomer pseudoephedrine and cathine from phenylpropanolamine in a single run, what allowed their direct quantification in urine.

Ostéogénèse atypique après séquestrectomies multiples pour fracture ouverte infectée du fémur: un cas [Atypical osteogenesis following multiple sequestrectomies for infected open fracture of the femur: a case]

The authors present the case of an open fracture of femur Cauchoix type II with an infection due to Escherichia coli, Clostridium perfringens, Enterococcus and Aspergillus fumigatus. After several sequestrectomies and five hyperbaric sessions, apyrexia was attained at the end of the third month, the femur having been stabilised with an external fixator. The 15 cm gap due to loss of bone substance, filled at each dressing with an antiseptic iodine based ointment, closed itself finishing as continuous bone five months after the accident, the granulation tissue having been recovered by thin skin grafts. A repeated fracture occurring forty-eight hours after the removal of the Hoffmann frame was treated by fitting an Ilizarov fixator arriving at consolidation in seven months. The authors examine different possibilities of accelerating osteogenesis and highlight the potential role of iodine ointment as inductive to osteogenesis stemming from a periosteal layer seemingly held in place.

Official Positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®).

Given the significant impact the use of glucocorticoids can have on fracture risk independent of bone density, their use has been incorporated as one of the clinical risk factors for calculating the 10-year fracture risk in the World Health Organization's Fracture Risk Assessment Tool (FRAX(®)). Like the other clinical risk factors, the use of glucocorticoids is included as a dichotomous variable with use of steroids defined as past or present exposure of 3 months or more of use of a daily dose of 5 mg or more of prednisolone or equivalent. The purpose of this report is to give clinicians guidance on adjustments which should be made to the 10-year risk based on the dose, duration of use and mode of delivery of glucocorticoids preparations. A subcommittee of the International Society for Clinical Densitometry and International Osteoporosis Foundation joint Position Development Conference presented its findings to an expert panel and the following recommendations were selected. 1) There is a dose relationship between glucocorticoid use of greater than 3 months and fracture risk. The average dose exposure captured within FRAX(®) is likely to be a prednisone dose of 2.5-7.5 mg/day or its equivalent. Fracture probability is under-estimated when prednisone dose is greater than 7.5 mg/day and is over-estimated when the prednisone dose is less than 2.5 mg/day. 2) Frequent intermittent use of higher doses of glucocorticoids increases fracture risk. Because of the variability in dose and dosing schedule, quantification of this risk is not possible. 3) High dose inhaled glucocorticoids may be a risk factor for fracture. FRAX(®) may underestimate fracture probability in users of high dose inhaled glucocorticoids. 4) Appropriate glucocorticoid replacement in individuals with adrenal insufficiency has not been found to increase fracture risk. In such patients, use of glucocorticoids should not be included in FRAX(®) calculations.

Travail bilingue et intégré des savoirs disciplinaires et linguistiques: apprentissage dans l'enseignement bilingue au secondaire II

Trois constats majeurs sont à l'origine de notre étude. Premièrement, les processus d'acquisition mobilisés par l'enseignement bilingue ont fait l'objet de très peu de recherches, alors que les résultats issus de ce type d'enseignement ont été largement explorés et ont globalement reçu une évaluation positive. Deuxièmement, l'apprentissage de la langue seconde (L2) et le bénéfice qu'il peut tirer d'un enseignement bilingue reste l'objet privilégié pour la plupart des études, alors que les particularités et les enjeux de l'apprentissage des disciplines dites "non linguistiques" (DNL) (telles l'histoire, la physique ou les mathématiques) restent largement inexplorées. Troisièmement, l'intégration a été souvent étudiée au niveau du curriculum scolaire pour dégager les interrelations entre enseignement de la L2 et enseignement des DNL, mais l'intégration demandait encore à être décrit de manière détaillée en tant qu'incorporation de l'apprentissage des savoirs disciplinaires et linguistiques et en tant que travail intégré des savoirs linguistiques et disciplinaires.Notre analyse s'inscrit alors dans une triple perspective prenant en compte ces trois axes de recherche : une perspective interactionniste et située de l'apprentissage des langues permettant d'envisager les processus d'acquisition mobilisés par l'enseignement bilingue in situ ; une perspective bi-plurilingue qui invite à étudier les spécificités de l'enseignement bilingue et s'affilie à une didactique du plurilinguisme valorisant un travail bilingue et intégré en classe ; une perspective des DNL permettant de considérer les enjeux de l'enseignement bilingue pour l'apprentissage des DNL, et non seulement pour l'apprentissage de la L2, et de considérer le travail intégré des savoirs linguistiques et disciplinaires.Ainsi, notre étude vise la description des pratiques effectives en classe bilingue s'appuyant sur l'analyse d'un important corpus d'interactions enregistrées dans diverses classes du secondaire II, orientée vers une méthodologie à caractère ethnographique et basée sur une démarche empirique et descriptive, ainsi que sur les outils de l'analyse conversationnelle appliquée à l'apprentissage des L2.Dans ce contexte, notre travail repose sur l'hypothèse que l'enseignement bilingue profite non seulement à l'apprentissage des savoirs linguistiques, mais également à celui des savoirs disciplinaires, lorsqu'il se base sur un travail intégré de la dimension linguistique et disciplinaire de cet apprentissage, et qu'un travail dans les deux langues en présence contribue à une intégration forte des savoirs linguistiques et disciplinaires. Il vise alors l'examen de l'articulation entre travail disciplinaire et travail linguistique dans différentes DNL et activités, ainsi que l'élaboration bilingue des concepts disciplinaires.D'abord, nos analyses montrent deux manières d'aborder l'élaboration des concepts disciplinaires dans les classes bilingues observées, le mode unilingue et le mode bilingue, et mettent en lumière l'apport du mode bilingue ou travail bilingue à l'élaboration des savoirs disciplinaires. Puis, la description détaillée de séquences-types permet de dégager les fonctionnements spécifiques à un enseignement bilingue et intégré, ainsi que les degrés et les procédés d'intégration des savoirs linguistiques et disciplinaires dans l'apprentissage en classe bilingue.En résumé, nos observations montrent que le bénéfice de l'enseignement bilingue réside dans l'attention particulière portée aux enjeux linguistiques des DNL et dans le travail linguistique, lorsqu'il est orienté vers un but disciplinaire. Aussi, cette orientation s'affirme dans la dynamique entre travail sur la dimension disciplinaire et travail sur la dimension linguistique.

Evolutionary patterns of MHC class II B in owls and their implications for the understanding of avian MHC evolution

Owing to its special mode of evolution and central role in the adaptive immune system, the major histocompatibility complex (MHC) has become the focus of diverse disciplines such as immunology, evolutionary ecology, and molecular evolution. MHC evolution has been studied extensively in diverse vertebrate lineages over the last few decades, and it has been suggested that birds differ from the established mammalian norm. Mammalian MHC genes evolve independently, and duplication history (i.e., orthology) can usually be traced back within lineages. In birds, this has been observed in only 3 pairs of closely related species. Here we report strong evidence for the persistence of orthology of MHC genes throughout an entire avian order. Phylogenetic reconstructions of MHC class II B genes in 14 species of owls trace back orthology over tens of thousands of years in exon 3. Moreover, exon 2 sequences from several species show closer relationships than sequences within species, resembling transspecies evolution typically observed in mammals. Thus, although previous studies suggested that long-term evolutionary dynamics of the avian MHC was characterized by high rates of concerted evolution, resulting in rapid masking of orthology, our results question the generality of this conclusion. The owl MHC thus opens new perspectives for a more comprehensive understanding of avian MHC evolution.

Closed and open grade I and II tibial shaft fractures treated by reamed intramedullary nailing

RESUME Objectif : Le but de cette étude est d'évaluer les résultats du traitement par enclouage centre-médullaire alésé des fractures diaphysaires du tibia aussi bien fermées que pour les fractures ouvertes de stade I et II selon Gustillo. Méthodes: Entre 1997 et 2000, 119 patients présentant une fracture diaphysaire du tibia ont été traités dans notre service par un enclouage centre-médullaire alésé. En postopératoire, 96 patients, soit 70 fractures fermées et 26 fractures ouvertes I et II selon Gustillo, ont été suivis cliniquement et radiologiquement pour une période de plus d'une année et demi. L'introduction du clou centro-médullaire a été faite selon la technique habituelle, soit transtendineuse ou paratendineusé rotulienne. Tous les clous ont été alésés jusqu'à 1,5 mm au-dessus du diamètre du clou. Les patients ayant une fracture isolée du tibia ont été immédiatement mobilisés en charge partielle pour une période de 6 semaines. Ceux qui avaient des lésions associées, notamment au niveau de la cheville épsilatérale, ont nécessité la mise en place d'un plâtre de Type Sarmiento. Résultats : Six patients (6,3%) ont développé un syndrome des loges après chirurgie. Quarante-huit cas (50%) ont nécessité une dynamisation du clou après une période moyenne de 12 semaines en raison d'un retard de consolidation. En général, 90,6% des fractures ont consolidé après 24 semaines postopératoires en moyenne, sans aucune différence significative entre les fractures fermées et les fractures ouvertes. Deux patients (2,1 %) présentant une fracture ouverte degré II ont développé une infection profonde ayant nécessité un traitement. Nous avons également observé 9,4% de cals vicieux minimes et sans conséquence clinique. Huit patients (8,3%) ont eu une brisure des vis de .verrouillage mais également sans conséquence clinique. Au dernier contrôle, 52% des patients, dont ('introduction du clou s'est faite en transtendineux ont des douleurs antérieures du genou contre 14% parmi ceux où l'introduction était paratendineuse. Conclusion : L'enclouage centre-médullaire reste le traitement de choix pour les fractures diaphysaires du tibia, qu'elles soient fermées ou ouvertes degré I ou II selon Gustillo.

Itinéraire clinique en traumatologie, une mode ou un besoin [Clinical pathway in traumatology, a fashion or need?].

A clinical route is defined as a "set of methods and instruments to members of a multidisciplinary and Interprofessional team to agree on the tasks for a specific patient population. This is a program of care to ensure the provision of quality care and efficient realization". The University Hospital is not immune to this phenomenon. In the Department of the musculoskeletal system, a first project of this kind concerns the fracture of the proximal femur in the elderly.

Clinical effectiveness of direct class II restorations: a meta-analysis.

Purpose: More than five hundred million direct dental restorations are placed each year worldwide. In about 55% of the cases, resin composites or compomers are used, and in 45% amalgam. The longevity of posterior resin restorations is well documented. However, data on resin composites that are placed without enamel/dentin conditioning and resin composites placed with self-etching adhesive systems are missing. Material and Methods: The database SCOPUS was searched for clinical trials on posterior resin composites without restricting the search to the year of publication. The inclusion criteria were: (1) prospective clinical trial with at least 2 years of observation; (2) minimum number of restorations at last recall = 20; (3) report on dropout rate; (4) report of operative technique and materials used; (5) utilization of Ryge or modified Ryge evaluation criteria. For amalgam, only those studies were included that directly compared composite resin restorations with amalgam. For the statistical analysis, a linear mixed model was used with random effects to account for the heterogeneity between the studies. P-values under 0.05 were considered significant. Results: Of the 373 clinical trials, 59 studies met the inclusion criteria. In 70% of the studies, Class II and Class I restorations had been placed. The overall success rate of composite resin restorations was about 90% after 10 years, which was not different from that of amalgam. Restorations with compomers had a significantly lower longevity. The main reason for replacement were bulk fractures and caries adjacent to restorations. Both of these incidents were infrequent in most studies and accounted only for about 6% of all replaced restorations after 10 years. Restorations with macrofilled composites and compomer suffered significantly more loss of anatomical form than restorations with other types of material. Restorations that were placed without enamel acid etching and a dentin bonding agent showed significantly more marginal staining and detectable margins compared to those restorations placed using the enamel-etch or etch-and-rinse technique; restorations with self-etching systems were between the other groups. Restorations with compomer suffered significantly more chippings (repairable fracture) than restorations with other materials, which did not statistically differ among each other. Restorations that were placed with a rubber-dam showed significantly fewer material fractures that needed replacement, and this also had a significant effect on the overall longevity. Conclusion: Restorations with hybrid and microfilled composites that were placed with the enamel-etching technique and rubber-dam showed the best overall performance; the longevity of these restorations was similar to amalgam restorations. Compomer restorations, restorations placed with macrofilled composites, and resin restorations with no-etching or self-etching adhesives demonstrated significant shortcomings and shorter longevity.

Calcium revisited: part II calcium supplements and their effects.

Calcium supplements were tested in pregnancy and lactation, in childhood and adolescence, in pre- and postmenopausal women and in elderly persons with various effects on bone density and fracture incidence. They must be properly chosen and adequately used. In this case, the reported minor negative side-effects do not restrict their use. All these aspects are reviewed here.