Development of inhaled moxifloxacin-metformin formulation as an alternative for pulmonary tuberculosis treatment.

Resistant M. tuberculosis strains threaten pulmonary tuberculosis (P-TB) control since they limit drug options. Drug repositioning and new development strategies are urgently required to overcome resistance. Studies have already shown the beneficial role of the oral antidiabetic metformin as an anti-tuberculosis adjuvant drug. This work aimed to develop an inhalatory dry powder co-formulation of metformin and moxifloxacin to figure out a future option for P-TB treatment. Pre-formulation evaluations indicated the physicochemical compatibility of constituents, demonstrating powder crystallinity and acceptable drug content. Eight moxifloxacin-metformin dry powder formulations were produced by spray drying, and solid-state characterizations showed partial amorphization, ascribed to moxifloxacin. Four formulations containing L-leucine exhibited micromeritic and in vitro deposition profiles indicating pulmonary delivery suitability, like spherical and corrugated particle surface, geometric diameters < 5 µm, high emitted doses (>85 %), and mass median aerodynamic diameters between 1-5 µm. The use of a second spray dryer model further optimized the aerodynamic properties and yield of the best formulation, demonstrating the influence of the equipment used on the product obtained. Moreover, the final formulation showed high in vitro cell tolerability and characteristics in permeability studies indicative of good drug retention in the lungs.

Impact of Resin Composite Viscosity and Fill-technique on Internal Gap in Class I Restorations: An OCT Evaluation.

The aim of this in vitro study was to quantitatively evaluate the internal gap of resin composites of high-and low-viscosity used in single- and incremental-fill techniques in Class I cavities exposed to thermal cycling (TC) using optical coherence tomography (OCT). Cavities of 4-mm depth and 3-mm diameter were prepared in 36 third molars randomly distributed into four groups, according to viscosity of restorative resin-based composite (high or low viscosity, all from 3M Oral Care) and technique application (bulk or incremental fill) used (n=9): RC, high-viscosity, incremental-fill, resin-based composite (Filtek Z350 XT Universal Restorative); BF, high-viscosity, bulk-fill, resin-based composite (Filtek One Bulk Fill); LRC, lowviscosity, incremental-fill, resin-based composite (Filtek Z350 XT Flowable Universal Restorative); and LBF, low-viscosity, bulk-fill, resin-based composite (Filtek Flowable Restorative). Single Bond Universal Adhesive system (3M Oral Care) was used in all the experimental groups. The incremental-fill technique was used for RC and LRC groups (2-mm increments), and a single-layer technique was used for BF and LBF groups, as recommended by the manufacturer. The internal adaptation of the resin at all dentin walls was evaluated before and after TC (5000 cycles between 5°C and 55°C) using OCT images. Five images of each restored tooth were obtained. Images were analyzed using ImageJ software that measured the entire length of the gaps at the dentin-restoration interface. The length of gaps (µm) was analyzed using two-way repeated measures ANOVA and the Tukey tests (α=0.05). There was a significant interaction between material types and TC (p=0.006), and a significant difference among all material types (p<0.0001), before and after TC (p<0.0001). Increased internal gaps at the dentin-restoration interface were noticed after TC for all groups. RC presented the lowest value of internal gap before and after TC, while LBF showed the highest values of internal gap after TC. In conclusion, TC negatively affected the integrity of internal gap, whereas high-viscosity, incremental-fill, resin-based composite presented better performance in terms of internal adaptation than low-viscosity, bulk-fill materials in Class I cavities.

First occurrence of Arnold Chiari type II malformation and associated abnormalities in a Gir calf produced in vitro from Brazil - case report / [Primeira ocorrência de malformação de Arnold Chiari tipo II e anormalidades associadas em uma bezerra Gir de produção in vitro no Brasil - relato de caso]

This study characterized the clinical, radiological, ultrasound, and necroscopic findings of a case of Arnold-Chiari type II malformation in a Gir breed calf from Brazil. The animal was hospitalized at sixty days of age, in permanent sternal recumbency, cutaneous appendix at the 4th lumbar vertebra and kyphoscoliosis of the caudal and lumbosacral thoracic spine. Radiographic examination of the spine and skull revealed spina bifida and suspected occipital hypoplasia. Upon examination of myelography with an injection of lumbar and atlantooccipital contrast, it was possible to visualize the meningocele at the 4th lumbar vertebra region and findings at the rhombencephalon level of increased regional pressure with failure to fill the contrast in the posterior fossa, in the presence of clear demarcation of the circumvolutions of the cerebral cortex and the subarachnoid space of the cervical spinal cord. Ultrasonographic examination of the cerebellum showed an insinuation of the cerebellar worm through the foramen magnum. The animal did not show changes in complete blood count, biochemical series, and cerebrospinal fluid and was negative for Pestivirus. There was a worsening of the clinical conditions and the animal died. This malformation of unknown etiology must be studied as a differential diagnosis of the nervous system disorders.(AU)

Este estudo caracterizou os achados clínicos, radiológicos, ultrassonográficos e necroscópicos de um caso de malformação de Arnold-Chiari tipo II em uma bezerra Gir no Brasil. O animal foi hospilatizado aos 60 dias de idade, apresentando decúbito esternal permanente, apêndice cutâneo na altura da quarta vértebra lombar e cifoescoliose da coluna vertebral torácica caudal e lombossacra. Ao exame radiográfico da coluna e do crânio, foram observadas espinha bífida e suspeita de hipoplasia occipital. Ao exame de mielografia com injeção de contraste lombar e atlanto-occipital, foi possivel visualizar a meningocele na altura da quarta vértebra lombar e achados em nível rombencefálico de aumento da pressão regional com falha de preenchimento do contraste na fossa posterior, na presença de nítida demarcação das circunvoluções do córtex cerebral e do espaço subaracnoide da medula espinhal cervical. Ao exame ultrassonográfico do cerebelo, foi observada insinuação do verme cerebelar através do forame magno. O animal não apresentou alterações em hemograma completo, série bioquímica e fluido cérebro-espinhal e foi negativo para Pestivirus. Houve uma piora do quadro clínico e o animal morreu. Essa malformação de etiologia desconhecida deve ser estudada como um diagnóstico diferencial.(AU)

Tuning the magnetic properties of Sn1-x-y Ce4+x Ce3+y O2 nanoparticles: an experimental and theoretical approach.

During the last decade, there was a substantial increase in the research on metal-doped oxide semiconductor nanoparticles due to advances in the engineering of nanomaterials and their potential application in spintronics, biomedicine and photocatalysis fields. In this regard, doping a nanomaterial is a powerful tool to tune its physicochemical properties. The aim of this work is to shine a new light on the role of the neighbouring elements on the oxidation state of the Ce-impurity, from both experimental and theoretical points of view. Herein, we present an accurate study of the mechanisms involved in the oxidation states of the Ce-ions during the doping process of SnO2 nanoparticles (NPs) prepared by the polymeric precursor method. X-ray diffraction measurements have displayed the tetragonal rutile-type SnO2 phase in all samples. However, the Bragg's peak (111) and (220) located at 2θ ∼29° and ∼47° evidence the formation of a secondary CeO2 phase for samples with Ce content up to 10%. X-ray absorption near-edge structure (XANES) measurements, at Ce L3 edge, were performed on the NPs as a function of Ce content. The results show, on one side, the coexistence of Ce3+ and Ce4+ states in all samples; and on the other side, a clear reduction in the Ce3+ population driven by the increase of Ce content. It is shown that this is induced by the neighboring cation, and confirmed by magnetic measurements. The monotonic damping of the Ce3+/Ce4+ ratio experimentally, was connected with theoretical calculations via density functional theory by simulating a variety of point defects composed of Ce impurities and surrounding oxygen vacancies. We found that the number of oxygen vacancies around the Ce-ions is the main ingredient to change the Ce oxidation state, and hence the magnetic properties of Ce-doped SnO2 NPs. The presented results pave the way for handling the magnetic properties of oxides through the control of the oxidation state of impurities.

The Role Of Comorbidities On Outcome Prediction In Acute Burn Patients.

Burn trauma is a leading cause of mortality and morbidity. None of the currently available formulas for mortality prediction take into account the impact of comorbidities on burn patients' outcome. In this study, we evaluate the impact of comorbidities on in-hospital mortality and prolonged length of hospital stay (≥30 days). A retrospective analysis of burn patients' medical records, over a 5-year period, was undertaken. A total of 677 patients were included. The mortality rate was 6.5%. Deceased patients and survivors with length of hospital stay (LOS) of 30 or more days were significantly older, had larger %TBSA burned, were more likely to have inhalation injury and comorbidities, and had higher Charlson Comorbidity Index (CCI) scores. On the multivariate logistic regression models, age, %TBSA burned, CCI score and the presence of inhalation injury were independently associated with mortality and prolonged LOS. In conclusion, the authors suggest that the inclusion of comorbidities should be considered on burn admission scores in an attempt to better predict burn mortality.

Les brûlures sont responsables de morbidité et de mortalité élevées. Aucun des scores prédictifs actuels ne prend en compte les comorbidités des patients. Cette étude évalue leur impact sur le devenir et la durée d'hospitalisation prolongée (≥30 jours). Il s'agit d'une étude rétrospective fondée sur l'analyse des dossiers de 667 patients hospitalisés pendant une période de 5 ans, chez lesquels la mortalité s'est avérée être de 6,5%. Les patients décédés et à la durée de séjour ≥30 jours étaient significativement plus âgés, brûlés sur une plus grande surface, avaient plus fréquemment inhalé des fumées et avaient plus de comorbidités (reflétées par un score de Charlson- SCh- plus élevé). En analyse multivariée, l'âge, la surface brûlée, l'inhalation de fumées et le SCh était des facteurs indépendants de séjour prolongé et de mortalité. Les auteurs suggèrent donc d'inclure les comorbidités dans les scores prédictifs concernant les brûlés.

Multicentric chondrosarcoma involving the appendicular skeleton: a case report and literature review.

Chondrosarcomas constitute the 3rd most common primary bone malignancy. These tumours grow slowly and rarely metastasize, usually having a good prognosis after surgery. Among patients registered and treated at the Brazilian National Institute of Traumatology and Orthopedics, an uncommon case of chondrosarcoma was identified in a 63-year-old man, who was diagnosed with multicentric chondrosarcoma of the appendicular skeleton. This example is atypical in the medical literature because multicentric tumours are different from metastatic events, and their frequency in chondrosarcoma is rare. This article therefore provides a rare case report alongside a review of additional cases in the medical literature.

Weight adjustment equation for hair sheep raised in warm conditions.

To estimate the nutritional requirements of hair sheep, knowledge about the animal's weight and its relationships with growth performances is essential. A study was carried with the objective to establish the relationships between BW, fasting BW (FBW), empty BW (EBW), average daily gain (ADG) and empty BW gain (EBWG) for hair sheep in growing and finishing phases in Brazilian conditions. Databases were obtained from 32 studies, for a total of 1145 observations; there were 3 sex classes (non-castrated male, castrated male and female) and 2 feeding systems (pasture and feedlot). The most representative breeds in the database were Santa Ines (n = 473), Morada Nova (n = 70) and Brazilian Somali (n = 47). The other animals in the database were crossbreeds (n = 555). The FBW (kg), EBW and EBWG (kg/day) were estimated according to linear regression. A random coefficient model was adopted, considering the study as a random effect and including the possibility of covariance between the slope and the intercept. The coefficients obtained from the linear regression of the FBW against the BW, EBW against the FBW and EBWG against the ADG did not differ between sex class (P > 0.05) and genotype (P > 0.05). The equations generated to estimate FBW from the BW, EBW from the FBW and EBWG from the ADG are as follows: FBW = -0.5470 (±0.2025) + 0.9313(±0.019) × BW, EBW = -1.4944 (±0.3639) + 0.8816 (±0.018) × FBW and EBWG = 0.906 (±0.019) × ADG, respectively. The low mean squared error values found in the cross-validation confirmed the reliability of these equations. Considering a sheep with a BW of 30 kg and a 100 g ADG, the estimated FBW, EBW and EBWG calculated using the generated equations are 27, 22.65 and 0.090 kg, respectively. In conclusion, the generated equations can be used in growing hair sheep. The validation procedure applied to the generated equations showed that its use for hair sheep seems to be appropriate.

Tailoring the physical and chemical properties of Sn1-xCoxO2 nanoparticles: an experimental and theoretical approach.

In this work, we present a coupled experimental and theoretical first-principles investigation on one of the more promising oxide-diluted magnetic semiconductors, the Sn1-xCoxO2 nanoparticle system, in order to see the effect of cobalt doping on the physical and chemical properties. Our findings suggest that progressive surface enrichment with dopant ions plays an essential role in the monotonous quenching of the surface disorder modes. That weakening is associated with the passivation of the oxygen vacancies as the Co excess at the surface becomes larger. Room-temperature 119Sn Mössbauer spectroscopy data analysis revealed the occurrence of a distribution of isomer shifts, related to the different non-equivalent surroundings of Sn4+ ions and the coexistence of Sn2+/Sn4+ at the particle surfaces provoked by the inhomogeneous distribution of Co ions, in agreement with the X-ray photoelectron spectroscopy measurements. Magnetic measurements revealed a paramagnetic behavior of the Co ions dispersed in the rutile-type matrix with antiferromagnetic correlations, which become stronger as the Co content is increased. Theoretical calculations show that a defect with two Co mediated by a nearby oxygen vacancy is the most likely defect. The predicted effects of this defect complex are in accordance with the experimental results.

The Centre for Data and Knowledge Integration for Health (CIDACS): Linking Health and Social Data in Brazil.

The Centre for Data and Knowledge Integration for Health (CIDACS) was created in 2016 in Salvador, Bahia-Brazil with the objective of integrating data and knowledge aiming to answer scientific questions related to the health of the Brazilian population. This article details our experiences in the establishment and operations of CIDACS, as well as efforts made to obtain high-quality linked data while adhering to security, ethical use and privacy issues. Every effort has been made to conduct operations while implementing appropriate structures, procedures, processes and controls over the original and integrated databases in order to provide adequate datasets to answer relevant research questions. Looking forward, CIDACS is expected to be an important resource for researchers and policymakers interested in enhancing the evidence base pertaining to different aspects of health, in particular when investigating, from a nation-wide perspective, the role of social determinants of health and the effects of social and environmental policies on different health outcomes.

Aging and burn: a five-year retrospective study in a major burn centre in Portugal.

Aging is an important factor contributing decisively to the clinical outcome of burn patients. The aim of this study was to assess the characteristics of patients admitted to a Burn Unit and determine the impact of aging on mortality. A retrospective analysis of patients successively admitted to a major burn centre in Portugal from 1/1/2012 to 31/12/2016 was conducted. They were divided into 2 groups: "elderly" (≥65 years) and "non-elderly" (<65 years). A total of 736 patients were included, 324 of them classified as elderly with a mean age of 78.12±7.14 years. Most of the patients in the elderly group were female (59.6%), in contrast to the non-elderly group (35%; p<0.001). The elderly patients had a higher mean length of hospital stay (20.14±18.46 days; p=0.011). Most of the burns were caused by fire (58.3%) and scalding (36.1%) and mainly after home accidents. Elderly patients showed a higher mean of burn severity index (7.26; p<0.001) and 6.8% needed an amputation. Mortality rate was significantly higher in the elderly group (11.7%; p=0.001). Age (p<0.001; OR=1.169), a higher total burn surface area (p<0.001; OR=1.081), full-thickness burns (p=0.005; OR=11.985) and the need for mechanical ventilation (p<0.001; OR=16.856) were associated with a higher mortality risk and reached statistical significance after multivariate analysis. The functional and vital prognosis of patients admitted to a burn centre is affected by multiple factors. This study showed that age, higher TBSA, full-thickness burns and need for mechanical ventilation seem to increase the risk of mortality.

L'âge avancé est un facteur déterminant du devenir d'un patient brûlé. Le but de cette étude rétrospective était d'évaluer les caractéristiques des patients admis dans notre CTB entre le 1/1/2012 et le 31/12/2016 et de déterminer les conséquences de l'âge sur la mortalité. Il étaient divisé en groupe "senior", S ((≥65 ans) et "non senior", NS (< 65 ans). Trois cent vingt quatre des 736 patients étaient S. Dans ce groupe, l'âge moyen était de 78,12 +/- 18 ans. Dans le groupe S, les femmes étaient surreprésentées (59,6%) comparativement au groupe NS (35%, p < 0,001). Les patients S restaient plus longtemps à l'hôpital (20,14 +/- 18,46 j ; p = 0,011). Les brûlures par flamme (58,3%) étaient plus fréquentes que les ébouillantements (36,1%). Elles provenaient le plus souvent d'un accident domestique. L'ABSI (7,26) était plus élevé dans le groupe S (p < 0,001). L'âge (OR 1,169 ; p < 0,001), l'augmentation de la SB (OR 1,081 ; p < 0,001), la présence de brûlures profondes (OR 11,985 ; p = 0,005) et la nécessité de ventilation mécanique (OR 16,856 ; p < 0,001) étaient, en analyse multivariées, associés à la mortalité. Les pronostics vital et fonctionnel des patients admis en CTB sont associés à de multiples paramètres. Cette étude montre que l'âge, la surface brûlée, la présence de brûlures profondes et la nécessité de recours à la ventilation mécanique augmentent le risque létal.

The role of microsurgical flaps in primary burn reconstruction.

Despite the wide and growing use of microsurgery, its application in primary burn reconstruction is not very frequent as it faces a number of additional challenges in this setting. A retrospective analysis of the clinical records of all patients submitted to microvascular free tissue transfer for primary burn reconstruction over an 8-year period (from January 2009 to December 2016) was performed. An evaluation of the indications, timing, principles of flap selection, complications and outcomes of free tissue transfer in primary burn reconstruction was made. Fourteen patients required 18 microsurgical flaps for acute soft tissue reconstruction (1.1% of all patients admitted). 64.3% of the patients were male. The mean age was 59.64 years, and mean TBSA was 10.5%. The majority of the injuries were caused by flames (71.4%), followed by electrical contact (21.4%). The primary indication for microsurgical reconstruction was tissue deficit with exposure of tendons, nerves, vessels, bone and/or joints after debridement. The procedure was more often performed in the early period after injury (between the 5th and 22nd day). The most frequently used flaps were the Latissimus dorsi and the anterolateral thigh flap. Major complications included 2 total flap failures (11.1%) and a partial flap failure that required reconstruction with another free flap. Microsurgical free flaps have a valuable role in primary burn reconstruction. Despite the reported higher complication rate in this specific clinical scenario, their use may reduce the total number of surgeries needed to achieve wound closure.

Bien que de plus en plus utilisée, la microchirurgie est rarement utilisée dans la prise en charge initiale des brûlés, et doit faire face à plusieurs difficultés supplémentaires dans cette indication. Nous avons effectué une analyse rétrospective des dossiers de tous les patients brûlés entre janvier 2009 et décembre 2016 ayant bénéficié au stade d'un lambeau libre (LL). Nous avons évalué l'indication, le délai, la sélection du site donneur, les complications et l'évolution du lambeau. Quatorze patients (1,1% du total) dont 64,5% d'hommes ont bénéficié de 18 LL. L'âge moyen était de 59,64 ans, la surface brûlée de 10,5%. La majorité des brûlures (71,4%) étaient dues à une flamme, 21,4% à l'électricité. L'indication principale était l'exposition ostéo-articulaire ou d'éléments nobles (tendons, nerfs, vaisseaux) après excision. La réalisation du LL était précoce (J5-J22). Les sites donneurs étaient Latissimus dorsi et la région antéro-latérale de cuisse. Deux lambeaux ont totalement nécrosé, un partiellement, ce qui a nécessité la réalisation d'un second LL. Les LL ont une place dans la prise en charge initiale des brûlés. Bien de grevés d'un taux de complications plus élevé dans cette indication, ils peuvent permettre de diminuer le nombre d'interventions nécessaires à la cicatrisation.

Síndrome de Eisenmenger em um gato / Eisenmenger syndrome in cat

A 6-month-old female, 1.0kg, uncastrated female Persian cat was brought to the Veterinary Hospital at State University of Ceara, with a history of dyspnea, prostration, hyporexia and progressive weight loss for a month. On physical examination, systolic cardiac murmur, cyanosis and dyspnea were detected. Unfortunately, the cat died during oxygen therapy. Necropsy examination revealed an increase in cardiac silhouette and ventricular septal defect of 2cm in diameter. Macroscopically the lungs were collapsed, with absent and diffusely reddish blackish crepitus, and the liver with blackish red coalescent multifocal areas, interspersed with lighter areas and lobular pattern with irregular brownish multifocal areas intercepted by brownish areas. Thus, the necropsy results together with the history and physical examination of the animal confirmed the diagnosis of Eisenmenger Syndrome, becoming the report of the first case, in a cat, in Brazil.(AU)

Genomics of Parallel Experimental Evolution in Drosophila.

What are the genomic foundations of adaptation in sexual populations? We address this question using fitness-character and whole-genome sequence data from 30 Drosophila laboratory populations. These 30 populations are part of a nearly 40-year laboratory radiation featuring 3 selection regimes, each shared by 10 populations for up to 837 generations, with moderately large effective population sizes. Each of 3 sets of the 10 populations that shared a selection regime consists of 5 populations that have long been maintained under that selection regime, paired with 5 populations that had only recently been subjected to that selection regime. We find a high degree of evolutionary parallelism in fitness phenotypes when most-recent selection regimes are shared, as in previous studies from our laboratory. We also find genomic parallelism with respect to the frequencies of single-nucleotide polymorphisms, transposable elements, insertions, and structural variants, which was expected. Entirely unexpected was a high degree of parallelism for linkage disequilibrium. The evolutionary genetic changes among these sexual populations are rapid and genomically extensive. This pattern may be due to segregating functional genetic variation that is abundantly maintained genome-wide by selection, variation that responds immediately to changes of selection regime.

Electrical burns: a retrospective analysis over a 10-year period.

Although electrical burns have a rather low incidence, they are considered one of the most devastating injuries. The aim of this retrospective study was to analyse specific aspects of electrical injuries and to delineate a prevention strategy. A retrospective analysis of medical records of all the patients admitted to our Unit with electrical burns over a 10-year period (2006/01/01-2015/12/31) was undertaken. Demographic data, mechanism of injury and electric current voltage, total burn surface area (TBSA), location and depth of burns, acute complications, surgical interventions and length of hospital stay (LOS) were analysed. Out of 1695 burn patients admitted to our Unit, 99 subjects (5.84%) suffered electrical burns. 97% of these patients were male. The mean age was 38.3±13.7years and mean TBSA was 11.9%±13.2%. The mechanism of injury was occupational in 75 cases. Injuries were classified as low-voltage burns (24.2%), highvoltage burns (30.3%) and flash burns (45.5%). TBSA (p=0.014), mean LOS (p=0.002) and serum creatinine kinase levels (p<0.001) were significantly higher in patients with high-voltage injury in comparison to low-voltage injury, as well as the incidence of escharotomy/ fasciotomy (p=0.049) and flap surgeries (p=0.004). Although there was a higher incidence of amputations in this group (16.7% vs. 12.5%), the difference was not statistically significant (p=0.487). The high prevalence of electrical burns in males and workers emphasizes the need to review occupational safety regulations. Educational efforts regarding potential hazards of electricity and reinforcing compliance with safety measures are essential to avoid these injuri.

Bien que plutôt rares, les brûlures électriques sont considérées comme les plus délabrants des accidents. Le but de cette étude était d'analyser les aspects spécifiques des brûlures électriques et de définir une stratégie de prévention. Elle a consister en l'analyse des dossiers de tous les patients admis pour brûlure électrique entre le 1er janvier 2006 et les 31 décembre 2015. Les données démographiques, le mécanisme exact de l'accident, le voltage, la surface brûlée (SB), la localisation, la profondeur, les complications initiales, les interventions chirurgicales et la durée moyenne de séjour (DMS) ont été analysées. Quatre vingt dix neuf (5,84%) des 1 695 patients hospitalisés pour brûlure avaient subi un accident électrique, 97% d'entre eux étaient des hommes. Leur âge moyen était de 38,3 +/- 13,7 ans, la surface brûlée de 11,9 +/- 13,2%. Soixante quinze accidents étaient survenus au travail. On recensait 24,2% de brûlures électrothermiques par bas voltage, 30,3% par haut voltage et 45,5% de flashes. La surface brûlés (p=0,014), la DMS (p=0,002), le niveau de CPK sanguine (p<0,001), l'incidence des incisions de décharge et aponévrotomies (p=0,049) et de lambeaux (p=0,004) était plus élevés en cas d'atteinte par haut voltage. Bien que plus élevée chez ces patients (16,7% VS 12,5%), l'incidence des amputation n'était pas statistiquement significative (p=0,487). L'incidence élevée des accidents électriques chez les hommes au travail est une indication à revoir la législation. Des efforts de formation et de contrôle de l'application de la législation sont nécessaires pour éviter ces accidents.