Association strength of E6 to E6AP/p53 complex correlates with HPV-mediated oncogenesis risk.

Human papillomavirus (HPV) is recognized as the causative agent of cervical cancer in women, and it is associated with other anogenital and head/neck cancers. More than 120 types of HPV have been identified and many classified as high- or low-risk according to their oncogenic potential. One of its proteins, E6, has evolved to overcome the oncosuppressor functions of p53 by targeting this protein for degradation via interaction with the human ubiquitin-ligase E6AP. This study evaluates the correlation between the association strength of 40 HPV E6 types to the E6AP/p53 complex and the HPV oncogenesis risk using molecular simulations and machine and deep learning (ML/DL). In addition, a ML/DL-driven prediction is proposed for the HPV unclassified oncogenic risk type. The results indicate that thermodynamics play a pivotal role in the establishment of HPV-associated cancer and highlight the need to include some viral types in the HPV-related cancer surveillance and prevention strategies.

Structure-based computational design of antibody mimetics: challenges and perspectives.

The design of antibody mimetics holds great promise for revolutionizing therapeutic interventions by offering alternatives to conventional antibody therapies. Structure-based computational approaches have emerged as indispensable tools in the rational design of those molecules, enabling the precise manipulation of their structural and functional properties. This review covers the main classes of designed antigen-binding motifs, as well as alternative strategies to develop tailored ones. We discuss the intricacies of different computational protein-protein interaction design strategies, showcased by selected successful cases in the literature. Subsequently, we explore the latest advancements in the computational techniques including the integration of machine and deep learning methodologies into the design framework, which has led to an augmented design pipeline. Finally, we verse onto the current challenges that stand in the way between high-throughput computer design of antibody mimetics and experimental realization, offering a forward-looking perspective into the field and the promises it holds to biotechnology.

Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil.

The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we did not find an increased incidence of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sublineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting more infectious variants or antibody evasion mutations is expected to increase. IMPORTANCE The continuous evolution of SARS-CoV-2 is an expected phenomenon that will continue to happen due to the high number of cases worldwide. The present study analyzed how a Variant of Concern (VOC) could still circulate in a population hardly affected by two COVID-19 waves and with vaccination in progress. Our results showed that the answer behind that was a new generation of Gamma-like viruses, which emerged locally carrying mutations that made it more transmissible and more capable of spreading, partially evading prior immunity triggered by natural infections or vaccines. With thousands of new cases daily, the current pandemics scenario suggests that SARS-CoV-2 will continue to evolve and efforts to reduce the number of infected subjects, including global equitable access to COVID-19 vaccines, are mandatory. Thus, until the end of pandemics, the SARS-CoV-2 genomic surveillance will be an essential tool to better understand the drivers of the viral evolutionary process.

Immune evasion of SARS-CoV-2 variants of concern is driven by low affinity to neutralizing antibodies.

SARS-CoV-2 VOC immune evasion is mainly due to lower cross-reactivity from previously elicited class I/II neutralizing antibodies, while increased affinity to hACE2 plays a minor role. The affinity between antibodies and VOCs is impacted by remodeling of the electrostatic surface potential of the Spike RBDs. The P.3 variant is a putative VOC.

Are Zika virus cross-reactive antibodies against aquaporin-4 associated to Neuromyelitis Optica Spectrum Disorder?

Zika virus (ZIKV) infection has been associated with the development of Neuromyelitis Optica Spectrum Disorder (NMOSD). ZIKV-induced antibodies that putatively cross-react to aquaporin-4 (AQP4) protein are suggested to cause inflammation of the optic nerve. A region of similarity between AQP4 and the ZIKV NS2B protein was identified. Our data showed that ZIKV-associated NMOSD patients develop anti-AQP4 antibodies, but not anti-ZIKV NS2B antibodies, revealing that cross-reacting antibodies are not the underlying cause of this phenotype. ZIKV infection in mice showed persistent viral replication in the eye tissue, suggesting that NMOSD symptoms are consequence of viral infection of the optic nerve cells.

Identification of a Zika NS2B epitope as a biomarker for severe clinical phenotypes.

The identification of specific biomarkers for Zika infection and its clinical complications is fundamental to mitigate the infection spread, which has been associated with a broad range of neurological sequelae. We present the characterization of antibody responses in serum samples from individuals infected with Zika, presenting non-severe (classical) and severe (neurological disease) phenotypes, with high-density peptide arrays comprising the Zika NS1 and NS2B proteins. The data pinpoints one strongly IgG-targeted NS2B epitope in non-severe infections, which is absent in Zika patients, where infection progressed to the severe phenotype. This differential IgG profile between the studied groups was confirmed by multivariate data analysis. Molecular dynamics simulations and circular dichroism have shown that the peptide in solution presents itself in a sub-optimal conformation for antibody recognition, which led us to computationally engineer an artificial protein able to stabilize the NS2B epitope structure. The engineered protein was used to interrogate paired samples from mothers and their babies presenting Zika-associated microcephaly and confirmed the absence of NS2B IgG response in those samples. These findings suggest that the assessment of antibody responses to the herein identified NS2B epitope is a strong candidate biomarker for the diagnosis and prognosis of Zika-associated neurological disease.

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein.

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141-144, ∆211, and ∆256-258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern.

Molecular epidemiology and drug resistance of Acinetobacter baumannii isolated from a regional hospital in the Brazilian Amazon region.

INTRODUCTION: In this study, we report a clonal dissemination of carbapenem resistant Acinetobacter baumannii isolates due to the acquisition of blaOXA-23 in a regional hospital located in Brazilian Amazon Region. METHODS: The isolates were identified by MALDI-TOF and the carbapenemase-encoding genes were detected by multiplex-PCR. The genetic similarity was investigated by pulsed-field gel electrophoresis (PFGE). RESULTS: Only 10 (55.6%) isolates harbored the gene bla OXA-23. PFGE analysis revealed that these isolates belong to a single clone. CONCLUSIONS: This dissemination strategy indicates the need for surveillance, adoption of control procedures defined in guidelines, and the careful administration of antimicrobials should be reinforced.

The influence of biotinylation on the ability of a computer designed protein to detect B-cells producing anti-HIV-1 2F5 antibodies.

Antibodies against the HIV-1 2F5 epitope are known as one of the most powerful and broadly protective anti-HIV antibodies. Therefore, vaccine strategies that include the 2F5 epitope in their formulation require a robust method to detect specific anti-2F5 antibody production by B cells. Towards this goal, we have biotinylated a previously reported computer-designed protein carrying the HIV-1 2F5 epitope aiming the further development of a platform to detect human B-cells expressing anti-2F5 antibodies through flow cytometry. Biophysical and immunological properties of our devised protein were characterized by computer simulation and experimental methods. Biotinylation did not affect folding and improved protein stability and solubility. The biotinylated protein exhibited similar binding affinity trends compared to its unbiotinylated counterpart and was recognized by anti-HIV-1 2F5 antibodies expressed on the surface of patient-derived peripheral blood mononuclear cells. Moreover, we present a high affinity marker for the identification of epitope-specific B cells that can be used to measure the efficacy of vaccine strategies based on the HIV-1 envelope protein.

Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region.

The clinical outcomes associated with Zika virus (ZIKV) in the Americas have been well documented, but other aspects of the pandemic, such as attack rates and risk factors, are poorly understood. We prospectively followed a cohort of 1453 urban residents in Salvador, Brazil, and, using an assay that measured immunoglobulin G3 (IgG3) responses against ZIKV NS1 antigen, we estimated that 73% of individuals were infected during the 2015 outbreak. Attack rates were spatially heterogeneous, varying by a factor of 3 within a community spanning 0.17 square kilometers. Preexisting high antibody titers to dengue virus were associated with reduced risk of ZIKV infection and symptoms. The landscape of ZIKV immunity that now exists may affect the risk for future transmission.

Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors.

Zika virus (ZIKV) emerged on a global scale and no licensed vaccine ensures long-lasting anti-ZIKV immunity. Here we report the design and comparative evaluation of four replication-deficient chimpanzee adenoviral (ChAdOx1) ZIKV vaccine candidates comprising the addition or deletion of precursor membrane (prM) and envelope, with or without its transmembrane domain (TM). A single, non-adjuvanted vaccination of ChAdOx1 ZIKV vaccines elicits suitable levels of protective responses in mice challenged with ZIKV. ChAdOx1 prME ∆TM encoding prM and envelope without TM provides 100% protection, as well as long-lasting anti-envelope immune responses and no evidence of in vitro antibody-dependent enhancement to dengue virus. Deletion of prM and addition of TM reduces protective efficacy and yields lower anti-envelope responses. Our finding that immunity against ZIKV can be enhanced by modulating antigen membrane anchoring highlights important parameters in the design of viral vectored ZIKV vaccines to support further clinical assessments.

Mapping Putative B-Cell Zika Virus NS1 Epitopes Provides Molecular Basis for Anti-NS1 Antibody Discrimination between Zika and Dengue Viruses.

B-cell epitope sequences from Zika virus (ZIKV) NS1 protein have been identified using epitope prediction tools. Mapping these sequences onto the NS1 surface reveals two major conformational epitopes and a single linear one. Despite an overall average sequence identity of ca. 55% between the NS1 from ZIKV and the four dengue virus (DENV) serotypes, epitope sequences were found to be highly conserved. Nevertheless, nonconserved epitope-flanking residues are responsible for a dramatically divergent electrostatic surface potential on the epitope regions of ZIKV and DENV2 serotypes. These findings suggest that strategies for differential diagnostics on the basis of short linear NS1 sequences are likely to fail due to immunological cross-reactions. Overall, results provide the molecular basis of differential discrimination between Zika and DENVs by NS1 monoclonal antibodies.

Molecular epidemiology and drug resistance of Acinetobacter baumannii isolated from a regional hospital in the Brazilian Amazon region

Abstract INTRODUCTION: In this study, we report a clonal dissemination of carbapenem resistant Acinetobacter baumannii isolates due to the acquisition of blaOXA-23 in a regional hospital located in Brazilian Amazon Region. METHODS: The isolates were identified by MALDI-TOF and the carbapenemase-encoding genes were detected by multiplex-PCR. The genetic similarity was investigated by pulsed-field gel electrophoresis (PFGE). RESULTS: Only 10 (55.6%) isolates harbored the gene bla OXA-23. PFGE analysis revealed that these isolates belong to a single clone. CONCLUSIONS: This dissemination strategy indicates the need for surveillance, adoption of control procedures defined in guidelines, and the careful administration of antimicrobials should be reinforced.

Total arthroplasty in displaced dysplastic hips with acetabular reconstruction and femoral shortening - technical note.

To describe a new procedure of total hip replacement in patient with severe developmental dysplasia of the left hip, using technique of acetabular reconstruction with autogenous bone grafts and subtrochanteric shortening femoral osteotomy. Total hip replacement done in January of 2003. The Eftekhar's classification was used and included type D, neglected dislocations. Bone graft incorporated in acetabular shelf and femoral osteotomy. Our contribution is the use of an Allis plate to better fix acetabular grafts, avoiding loosening, and cerclage around bone graft in femoral osteotomy site, which diminish pseudoarthrosis risk. This technique shows efficiency, allowing immediately resolution for this case with pain and range of motion of hip improvement. It also allows the acetabular dysplasia reconstruction, equalization of the limb length (without elevated risk of neurovascular lesion) and repairs the normal hip biomechanics due to the correction of the hip's center of rotation.

Descrever contribuições à técnica da cirurgia de artroplastia total em displasias do desenvolvimento do quadril grave, por meio da reconstrução acetabular com o uso de enxerto autólogo e encurtamento femoral feito com osteotomia subtrocantérica em V invertido. Paciente submetido a artroplastia total do quadril esquerdo em janeiro de 2003. Foi usada a classificação de Eftekhar e o paciente era do tipo D, luxação inveterada. Incorporação do enxerto no teto acetabular e osteotomia femoral. Acrescentamos a fixação do enxerto da cabeça femoral no acetábulo com placa do tipo Allis, que contribui para maior resistência do sistema, e a cerclagem com fio de aço no enxerto ósseo junto à osteotomia subtrocantérica, que diminui o risco de pseudoartrose. Essa técnica demonstrou eficácia e permitiu a resolução imediata do caso com melhoria da dor e da amplitude de movimento do quadril. Permitiu também a reconstrução do déficit ósseo acetabular, a recomposição do comprimento do membro (sem risco aumentado de lesão neurovascular) e a recuperação da biomecânica do quadril com a reparação do centro de rotação normal.

Avaliação da contaminação por Acinetobacter spp. em uma unidade de terapia intensiva / Evaluation of contamination by Acinetobacter spp. in an intensive care unit / Evaluación de la contaminación por Acinetobacter spp. en una unidad de cuidados intensivos

Justificativa e Objetivos: A relevância clínica das Infecções Relacionadas à Assistência à Saúde (Iras) ocasionadas pelo Acinetobacter spp. e a confirmação da existência de cepas com multirresistência no meio hospitalar mostram a necessidade de se conhecer melhor a epidemiologia dessas infecções, a fim de auxiliar a implantação de medidas mais efetivas de prevenção e controle deste patógeno. Objetivou-se avaliar a diversidade fenotípica e o perfil de sensibilidade de Acinetobacter spp. isolados de pacientes internados, de mãos de profissionais e de superfícies inanimadas em uma Unidade de Terapia Intensiva de um hospital público da região sudeste do estado do Pará. Métodos: As coletas das superfícies e das mãos dos profissionais foram realizadas utilizando swabs umedecidos em soro fisiológico estéril e friccionados por meio de rolamento. Para análise dos dados, foram utilizadas técnicas de estatística descritiva por meio de distribuições absolutas e percentuais. Resultados: Das 163 amostras coletadas, 87 (53,4%) foram das superfícies, 47 (28,8%) dos pacientes e 29 (17,8%) das mãos dos profissionais. Em 28% observou-se o crescimento de bactérias Gram-negativas, sendo o Acinetobacter baumannii a cepa mais prevalente, estando presente nos isolados clínicos de pacientes e nas superfícies após o processo de limpeza. O A. baumannii apresentou-se resistente a todos os antimicrobianos testados. Conclusão: O A. baumannii foi a única espécie do gênero Acinetobacter a ser encontrada, sendo tais cepas resistentes a todos os antibióticos testados.(AU)

Background and Objectives: The clinical relevance of Healthcare Associated Infections caused by Acinetobacter spp. and the confirmation of the existence of strains with multi-resistance in the hospital environment show the need to know better the epidemiology of these infections, in order to help the implantation of more effective measures of prevention and control of this pathogen. The objective of this study was to evaluate the phenotypic diversity and the sensitivity profile of Acinetobacter spp. isolated from inpatients, hands of professionals and inanimate surfaces in an Intensive Care Unit of a public hospital in the southeast region of the state of Pará. Methods: The professionals' hands and surfaces were collected using swabs moistened in sterile saline and rubbed by rolling. Data analysis was performed using descriptive statistics techniques using absolute and percentage distributions. Results: Of the 163 samples collected, 87 (53.4%) came from the surfaces, 47 (28.8%) from the patients and 29 (17.8%) from the hands of professionals. Growth of Gram-negative bacteria was observed in 28%, being Acinetobacter baumannii the most prevalent strain, present in the clinical isolates of patients and on the surfaces after the cleaning process. A. baumannii was resistant to all antimicrobials tested. Conclusion: A. baumannii was the only species of the genus Acinetobacter to be found, being such strains resistant to all antibiotics tested.(AU)

Justificación y Objetivos: La relevancia clínica de las infecciones relacionadas con el cuidado de la salud ocasionadas por el Acinetobacter spp. y la confirmación de la existencia de cepas con multirresistencia en el medio hospitalario implican la necesidad de conocer mejor la epidemiología de esas infecciones, a fin de auxiliar en la implantación de medidas más efectivas de prevención y control de este patógeno. El objetivo de este estudio fue evaluar la diversidad fenotípica y el perfil de sensibilidad de Acinetobacter spp. aislados de pacientes hospitalizados, de las manos de profesionales y de superficies inanimadas en una Unidad de Cuidados Intensivos de un hospital público en la región sureste del estado de Pará. Métodos: Las colectas de las superficies y de las manos de los profesionales se realizaron utilizando hisopos humedecidos en suero fisiológico estéril y frotados por medio de rodamiento. El análisis de los datos se realizó mediante técnicas de estadística descriptiva utilizando distribuciones absolutas y porcentuales. Resultados: De las 163 muestras recogidas, 87 (53,4%) fueron de las superficies, 47 (28,8%) de los pacientes y 29 (17,8%) de las manos de los profesionales. El crecimiento de bacterias Gram-negativas se observó en el 28,0%, siendo Acinetobacter baumannii la cepa más prevalente en los aislados clínicos de los pacientes y en las superficies después del proceso de limpieza. A. baumannii fue resistente a todos los antimicrobianos probados. Conclusiones: El A. baumannii fue la única especie del género Acinetobacter encontrada, siendo tales cepas resistentes a todos los antibióticos probados.(AU)

PROXIMAL FEMURAL VALGUS SUBTROCHANTERIC OSTEOTOMY FOR NON UNION OF TROCHANTERIC FRACTURES.

OBJECTIVES: To evaluate valgus subtrochanteric osteotomy for the treatment of trochanteric non-union. METHODS: A retrospective study of cases series. From 1998 September to 2009 January, seventeen (17) cases with a diagnosis of non-union of trochanteric fracture were re-operated by the hip group of the Ortophaedic And Traumatology service of the Hospital Geral de Goiania (HGG). The patients presented pain at the fracture site, a femoral varus angle of less than 120°, and non-union of the fracture in the 3(rd) months after the initial surgery. RESULTS: Patients with ages ranging from 30 to 73 years, with a maximum follow-up of 09 years and minimum of 09 years. The mean time from first surgery to osteotomy was six months. Bone union was observed in 16 patients, with a mean union time of 12 weeks after surgery. The mean hip varus angle was 105(0) (120(0) to 90(0)). After surgery, the mean hip valgus angle was 144(0) (155(0) to 135(0)). We had one unsuccessful case; a 78-year old patient who had osteogtomy, fixed with DHS of 150(0), with valgization to 154(0). After six months of follow-up without union of the fracture, it was decided to perform total cemented hip artroplasthy, without complications. CONCLUSION: Valgus subtrochanteric osteotomies can be indicated for the treatment of trochanteric treatment of pseudoarthroses, with good final results for bone union, avoiding the need for total hip artroplasthy and maintaining biological fixation, as well as reestablishing the mechanical and anatomical axis of the affected limb.

Osteotomia valgizante subtrocantérica do fêmur proximal para o tratamento da não consolidação das fraturas transtrocanterianas / Proximal femural valgus subtrochanteric osteotomy for non union of trochanteric fractures

OBJETIVOS: Avaliar a consolidação de pseudoartrose transtrocanteriana tratada com osteotomia de valgização subtrocantérica. MÉTODOS: Estudo retrospectivo de série de casos. No período de setembro de 1998 a janeiro de 2009 foram reoperados no Serviço de Ortopedia e Traumatologia do Hospital Geral de Goiânia (HGG), pelo grupo de quadril, 17 pacientes com diagnóstico de não consolidação de fratura transtrocanteriana. Apresentavam dor no local da fratura, ângulo de varismo do fêmur menor ou igual a 120° e não consolidação da fratura no terceiro mês do primeiro pós-operatório. RESULTADOS: Pacientes com idade variando entre 30 e 73 anos, com seguimento máximo de nove anos e mínimo de um ano. O tempo médio entre a primeira cirurgia e a osteotomia de correção foi de seis meses. A consolidação foi evidenciada em 16 pacientes. A média de consolidação foi de 12 semanas de pós-operatório. O ângulo de varização pré-operatório do quadril foi calculado e sua média foi de 105 º de varo, sendo o maior 120 º e o menor 90 º. O ângulo da valgização pós-operatório foi calculado e sua média foi de 144 º de valgo, sendo o maior de 155 º e o menor de 135 º. Tivemos um caso de insucesso: paciente de 78 anos, que realizou a osteotomia, fixada com DHS de 150 º, com valgização para 154 º, após seis meses de acompanhamento sem consolidação da fratura, foi optado por uma artroplastia total de quadril cimentada, sem intercorrências. CONCLUSÃO: As osteotomias valgizantes subtrocantéricas podem ser indicadas para o tratamento das pseudoartroses em fraturas transtrocantéricas, com bons resultados finais de consolidação, evitando a substituição protética e mantendo uma fixação biológica, além de restabelecer o eixo mecânico e anatômico do membro acometido.

OBJECTIVES: to evaluate valgus subtrochanteric osteotomy for the treatment of trochanteric non-union. METHODS: A retrospective study of cases series. From 1998 September to 2009 January, seventeen (17) cases with a diagnosis of non-union of trochanteric fracture were re-operated by the hip group of the Ortophaedic And Traumatology service of the Hospital Geral de Goiania (HGG). The patients presented pain at the fracture site, a femoral varus angle of less than 120°, and non-union of the fracture in the 3rd months after the initial surgery. RESULTS: Patients with ages ranging from 30 to 73 years, with a maximum follow-up of 09 years and minimum of 09 years. The mean time from first surgery to osteotomy was six months. Bone union was observed in 16 patients, with a mean union time of 12 weeks after surgery. The mean hip varus angle was 105(0) (120(0) to 90(0)). After surgery, the mean hip valgus angle was 144(0) (155(0) to 135(0)). We had one unsuccessful case; a 78-year old patient who had osteogtomy, fixed with DHS of 150(0), with valgization to 154(0). After six months of follow-up without union of the fracture, it was decided to perform total cemented hip artroplasthy, without complications. CONCLUSION: Valgus subtrochanteric osteotomies can be indicated for the treatment of trochanteric treatment of pseudoarthroses, with good final results for bone union, avoiding the need for total hip artroplasthy and maintaining biological fixation, as well as reestablishing the mechanical and anatomical axis of the affected limb.

Previsão de homicídios no Brasil: proposta de variável antecedente

Neste estudo, investigamos a capacidade de variáveis antecedentes, entre elas internações por agressão, na previsão do número de homicídios no Brasil. O objetivo principal desta pesquisa é suprimir a lacuna referente à defasagem de informações na divulgação sobre homicídios no país, permitindo assim análises conjunturais atualizadas. Para tanto, por intermédio do esquema rolling window e da abordagem model confidence set (MCS), investigamos se modelos de variáveis antecedentes apresentam desempenho preditivo superior ao conjunto de modelos univariados. Ao aplicar a abordagem MCS, considerando diferentes estatísticas de avaliação, funções de perda e janelas de estimação, encontramos fortes evidências da capacidade das variáveis antecedentes utilizadas fornecerem conteúdoinformacional adicional na previsão da dinâmica criminal brasileira, com modelos de variáveis antecedentes sistematicamente superando modelos univariados. Na média, os melhores modelos de variáveis antecedentes apresentam melhorias relativas ao benchmark random walk, de 60% em termos de raiz do erro quadrado médio (RMSE), erro absoluto médio (MAE) e desvio absoluto médio da média (MAD).

In this article we investigate the capacity of antecedent variables, among them admissions for aggression, in the prediction of the number of homicides in Brazil. The main objective is to eliminate a gap regarding the large time lag in the dissemination of information about these deaths in the country, allowing updated conjuncture analyzes. For this, through a "rolling window" scheme and "Model Confidence Set" approach, we investigate whether multivariate models with leading variables show forecast performance superior to a set of univariate models. In applying the MCS approach, considering different evaluation statistics, loss functions and estimation windows, we find strong evidence of the ability of the leading variables used to provide additional information content in the prediction of the Brazilian criminal dynamics, with models of leading variables systematically surpassing univariate models, especially in extended periods of forecasting. In general, improvements related to the benchmark Random walk model, in terms of RMSE, MAE and MAD, are of the order of 60%.

Uma Avaliação de impacto de política de segurança pública: o Programa Estado Presente do Espírito Santo / Texto para Discussão (TD) 2543 : Uma Avaliação de impacto de política de segurança pública : o Programa Estado Presente do Espírito Santo

Observou-se a diminuição de 10,2% no número de homicídios no estado do Espírito Santo, entre 2010 e 2014. Nesse período, foram feitos substanciais investimentos no saneamento do sistema prisional e na implementação do Programa Estado Presente em Defesa da Vida, focado na diminuição das mortes violentas intencionais. O objetivo deste trabalho é investigar se a política pública levada a cabo no estado impactou o número de homicídios, utilizando metodologia de controle sintético. Os resultados indicam que, se não fosse a política adotada, o número de homicídio aumentaria em 29% entre 2010 e 2014. Comparando-se os custos financeiros correspondentes à implantação da política com o valor estatístico das vidas poupadas, estimado por Cerqueira (2014), concluímos que cada real gasto gerou um ganho de bem-estar social equivalente a R$ 2,4.

Uma análise da base de dados do Sistema de Informação Hospitalar entre 2001 e 2018: dicionário dinâmico, disponibilidade dos dados e aspectos metodológicos para a produção de indicadores sobre violência

Este trabalho explora e analisa a base de dados do SIH/SUS ­ para tanto, foi desenvolvido em seis capítulos. O primeiro trata da base de dados do SIH e a sua utilização na literatura científica. O segundo versa acerca da análise longitudinal da disponibilidade dos dados do SIH. O terceiro apresenta os dicionários dinâmicos de dados elaborados ano a ano, incluindo o histórico, a evolução, a conceituação das variáveis existentes e também as mudanças estruturais ocorridas no período entre 2001 e 2018. O quarto capítulo, por sua vez, exibe as questões metodológicas envolvidas na utilização desta base de dados, bem como o cálculo de alguns indicadores que serão construídos e analisados. O quinto apresenta os resultados para os indicadores obtidos ­ nele também são feitas comparações de resultados a partir dos microdados da base do SIH, com as informações divulgadas via Tabnet, e do SIM, para efeito de avaliar a qualidade da informação disponibilizada nos microdados da base do SIH/SUS. Por fim, no último capítulo, são expostas as conclusões obtidas a respeito da base de dados do SIH.