Síndrome de Down é uma limitação que impõe múltiplos desafios não apenas para a criança mas também a todos os seus familiares. A síndrome de Down ocorre por conta de uma desordem cromossômica, que resulta na trissomia do cromossomo 21, tendo como fator de risco predominante a idade materna avançada, geralmente, acima de 35 anos. A educação destas crianças passou a ser obrigatória a partir da LDB 9.393/96, no qual garante a todos o direito a educação na escola regular de ensino. Porém, embora seja muito discutida, nota-se que ainda há dificuldades para a inclusão destes alunos, seja pelo despreparo dos professores ou pela falta de estrutura da escola. Por conta de sua dificuldade intelectual o processo de alfabetização e desenvolvimento torna-se comprometido dificultando a concentração e com isso o processo é mais demorado. Por isso é preciso que o professor tenha melhor preparo para integrar e auxiliar as crianças com Down na escola. Para que haja de fato uma aprendizagem satisfatória é essencial que o profissional conheça os métodos que contribuirão para que o aluno se adapte e adquira conhecimento, tornando indispensável a discussão a respeito da temática. A partir de uma pesquisa bibliográfica será analisado como ocorre o processo de aprendizagem destes alunos.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available. Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Periodic event-triggered control (PETC) is an appealing paradigm for the implementation of controllers on platforms with limited communication resources, a typical example being networked control systems. In PETC, transmissions over the communication channel are triggered by an event generator, which depends solely on the available plant and controller data and is only evaluated at given sampling instants to enable its digital implementation. In this paper, we consider the general scenario, where the controller communicates with the plant via multiple decoupled networks. Each network may contain multiple nodes, in which case a dedicated protocol is used to schedule transmissions among these nodes. The transmission instants over the networks are asynchronous and generated by local event generators. At given sampling instants, the local event generator evaluates a rule, which only involves the measurements and the control inputs available locally, to decide whether a transmission is needed over the considered network. Following the emulation approach, we show how to design local triggering generators to ensure input-to-state stability and $\mathcal {L}_p$ stability for the overall system based on a continuous-time output-feedback controller that robustly stabilizes the network-free system. The method is applied to a class of Lipschitz nonlinear systems, for which we formulate the design conditions as linear matrix inequalities. The effectiveness of the scheme is illustrated via simulations of a nonlinear example.

Constant-force contact-mode atomic force microscopy (AFM) relies on a feedback control system to regulate the tip–sample interaction during imaging. Due to limitations in actuators and control, the bandwidth of the regulation system is typically small. Therefore, the scan rate is usually limited in order to guarantee a desirable image quality for a constant-rate scan. By adapting the scan rate online, further performance improvement is possible, and the conditions to this improvement have been explored qualitatively in a previous study for a wide class of possible scan patterns. In this article, a quantitative assessment of the previously proposed adaptive scan scheme is investigated through experiments that explore the impact of various degrees of freedom in the algorithm. Further modifications to the existing scheme are proposed and shown to improve the closed-loop performance. The flexibility of the proposed approach is further demonstrated by applying the algorithm to tapping-mode AFM.

Ultra-high performance concrete (UHPC) is a durable material that can be used in constructing new and unique structural elements. This research utilizes UHPC to construct prefabricated shells that act as stay-in-place forms for bridge columns and eliminate the use of traditional formwork. These innovative structural elements reduce the on-site construction time, improve the structural performance of the column, and act as a protective layer in aggressive environments. Generally, during the construction process, the prefabricated UHPC shell is placed around the column reinforcement, which is fabricated using conventional methods. To connect the UHPC shell and column reinforcement with the footing and footing dowels, a step made of UHPC is utilized. The UHPC step connection is designed to shift the plastic hinge away from the column-to-footing interface. In the next stage, normal concrete is cast inside the shell, forming a concrete-filled UHPC shell. The final stage of construction involves placing and connecting a prefabricated cap-beam using the same UHPC step connection. The column specimen was tested under constant axial load and incremental lateral load. In this test, the UHPC shell cracked on the north side at a drift ratio of 3%; however, the column had a significant capacity and behaved similarly to a conventional reinforced concrete column during higher cycles of drift ratios. The test was completed after the column had reached a drift ratio of 7.5% when the first bar ruptured. No damage occurred in the footing and UHPC step which proved that the design was successful in shifting the plastic hinge away from the column-to-footing interface.

Abstract In the present work, interferometric unsteady state analysis of the thermogravitational technique is for the first time attempted in a microcolumn. In this way, three transport coefficients, diffusion, thermodiffusion and Soret coefficients can be obtained in a single experiment. Two different models — one from the Furry-Jones-Onsager theory and the other with the ‘forgotten effect’ included — have been tested for six different binary mixtures. These mixtures are the three binary pairs of the Benchmark of Fontainebleau— tetrahydronaphthalene-isobutylbenzene (THN-IBB), tetrahydronaphthalene-dodecane (THN-nC12) and isobutylbenzene-dodecane (IBB-nC12)—toluene-methanol dimethyl sulfoxide-water (DMSO-H20) and dimethyl sulfoxide-deuterated water (DMSO-D20). The first three benchmark binary mixtures are used to validate the inteferometric technique and also to establish when it is reasonable to treat a mixture as ideal, without considering the forgotten effect. After that, the three remaining mixtures are deeply analysed. In the end, the isotopic effect in the Soret coefficient will be highlighted through the DMSO-H20 and DMSO-D20 mixtures.

Precipitation hardening stainless steel 17-7PH with modified chemical composition was heat treated by modified RH950 condition. In this paper is presented the results of tests of microstructure and mechanical properties of precipitation hardened stainless steel 17-7PH with modified chemical composition, heat treated in modificated RH950 conditions. Regression analysis showed which variables are statistically significant in predicting the value of mechanical properties of the steel 17-7PH chemically modified composition.

The field of optimal design of linear elastic structures has seen many exciting successes that resulted in new architected materials and designs. With the availability of cloud computing, including high-performance computing, machine learning, and simulation, searching for optimal nonlinear structures is now within reach. In this study, we develop two convolutional neural network models to predict optimized designs for a given set of boundary conditions, loads, and volume constraints. The first convolutional neural network model is for the case of materials with a linear elastic response while the second developed model is for hyperelastic response where material and geometric nonlinearities are involved. For the nonlinear elastic case, the neo-Hookean model is utilized. For this purpose, we generate datasets, composed of the optimized designs paired with the corresponding boundary conditions, loads, and constraints, using topology optimization framework to train and validate both models. The developed models are capable of accurately predicting the optimized designs without requiring an iterative scheme and with negligible computational time. The suggested pipeline can be generalized to other nonlinear mechanics scenarios and design domains.

Increased antibiotic utilization in hospital is linked to higher total treatment costs, together with increased length of stay, surgery and emergency admission. The aim of our retrospective cohort study was to investigate predictors of antibiotic utilization per single patient from an intensive care unit (ICU) of a tertiary care, university hospital in Serbia. Average utilization of antibiotics per patient was 23.9 ± 20.4 defined daily doses (DDDs). Diagnosis of systemic infection increased antibiotics utilization per patient for 10.0 DDDs, positive blood culture for 5.4 DDDs, isolation of Pseudomonas spp. for 19.5 DDDs, isolation of Acinetobacter spp. for 6.3 DDDs and injury for 7.3 DDDs per patient. Each new day of hospitalization and each additional drug prescribed increased utilization for further 0.3 DDDs and 1.2 DDDs, respectively. Appropriate and limited use of antibiotics in ICU is of key importance for preserving their effectiveness and decrease of bacterial resistance.

Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients. IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017. The primary objective population included 358 patients with stage I-II, hormone receptor-positive, HER2-negative breast cancer. The recommended treatment plan and physician confidence were captured before and after receiving results for 70-GS and 80-GS. Treatment was started after obtaining results. The distribution of 70-GS High Risk (HR) and Low Risk (LR) patients was evaluated, in addition to the distribution of 80-GS compared to IHC status. The 70-GS classified 62.5% (n = 224/358) of patients as LR and 37.5% (n = 134/358) as HR. Treatment decisions were changed for 24.0% (n = 86/358) of patients after receiving 70-GS and 80-GS results. Of the LR patients initially prescribed CT, 71.0% (44/62) had CT removed from their treatment recommendation. Of the HR patients not initially prescribed CT, 65.1% (41/63) had CT added. After receiving 70-GS results, CT was included in 83.6% (n = 112/134) of 70-GS HR patient treatment plans, and 91.5% (n = 205/224) of 70-GS LR patient treatment plans did not include CT. For patients who disagreed with the treatment recommended by their physicians, most (94.1%, n = 16/17) elected not to receive CT when it was recommended. For patients whose physician-recommended treatment plan was discordant with 70-GS results, discordance was significantly associated with age and lymph node status. The IMPACt trial showed that treatment plans were 88.5% (n = 317/358) in agreement with 70-GS results, indicating that physicians make treatment decisions in clinical practice based on the 70-GS result. In clinically high risk, 70-GS Low Risk patients, there was a 60.0% reduction in treatment recommendations that include CT. Additionally, physicians reported having greater confidence in treatment decisions for their patients in 72% (n = 258/358) of cases after receiving 70-GS results. “Measuring the Impact of MammaPrint on Adjuvant and Neoadjuvant Treatment in Breast Cancer Patients: A Prospective Registry” (NCT02670577) retrospectively registered on Jan 27, 2016.

One of the frequently occurring tasks during the development of a warehouse management system is the implementation of a routing algorithm of some kind. Whether it is for guiding workers during order picking, routing delivery vehicles or for routing company representatives, this task has proven to be challenging in the technical as well as the social sense. In other words, the task is heavily dependent on various company-specific constraints and it directly dictates the way employees should do their job. This paper describes a strategic approach to the development and gradual integration process of such algorithms which makes sure that all constraints are satisfied and, more importantly, ensures that route suggestions are viewed by the employees as a helpful tool rather than a threat to their job. Described through a real-world case study in a medium-to-large warehouse, the routing efficiency is almost doubled in comparison to the previous approach and critical factors are analysed and discussed throughout different stages of the process.

<jats:p>NA</jats:p>

Instructions for administering some drugs and indications for their use raise certain dilemmas and controversies questioning the appropriateness of the treatment in this way. In this article, some controversies regarding the prescribing of statins in patients whose blood cholesterol level is normal and the use of anticoagulants in the elderly patients without blood clots prior to the treatment are described. Also, it is discussed about some controversies regarding the use of the insulin analogues in the treatment of patients with diabetes mellitus.