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Background Risk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement. Methods Paraffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n = 424), and a Dutch prospective clinical cohort called MST (n = 256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan–Meier method, log-rank tests and Cox’s proportional hazard models were used for survival analysis. Results In total, 648 HR-EC were included. No independent prognostic value of ER, PR, L1CAM, and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15–0.75). Conclusions We confirmed the prognostic impact of the molecular classification, age, stage, and adjuvant CTRT in a large cohort of high-risk EC. ER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.

Purpose of review Changes in molecular classification together with a deeper knowledge of both immune disregulation and phosphatidylinositol-3 kinase (PI3K) pathway alterations are leading to a new endometrial cancer treatment paradigm. This review will address the cutting-edge data in this field. Recent findings This article will cover the updated data in endometrial cancer molecular classification and its correlation with the outcomes in randomized clinical trials (e.g., PORTEC-3). Moreover, we will review the latest data regarding checkpoint blockade molecules (CPB) in the recurrent setting and how they are changing the treatment landscape. In addition, the role of the PI3K inhibitors, their activity, and toxicity profile will be described. Summary As result of the incorporation of molecular classification in our daily practice, the adjuvant treatment in endometrial cancer is rapidly evolving and leading to a new paradigm. The promising data observed with CPB in the recurrent setting have led to the food and drug administration approval of pembrolizumab as monotherapy and in combination with lenvatinib. Additionally, the current outcomes achieved with PI3K inhibitor agents encourage us to continue our clinical research to identify those patients who may benefit the most.

Introduction/Background* The molecular endometrial cancer (EC) classification has proven prognostic value and can direct adjuvant treatment decisions. Despite this, a relatively large group of EC is still molecularly unclassified (NSMP-EC). In this study we aimed to identify biomarkers among high-risk NSMP-EC patients with prognostic and/or predictive relevance. Methodology Paraffin-embedded tumour material (n=423) from the PORTEC-3 HREC trial were available for analysis. All patients with NSMP-EC were selected, hence those without pathogenic POLE mutations, mismatch repair deficiency and p53-abnormal immunohistochemistry (IHC). Protein expression of L1CAM, ER and PR (ongoing) were analysed by IHC using a 10% threshold for positivity. Tumour DNA was analysed for pathogenic somatic mutations using a next generation sequencing (NGS) cancer hotspot panel. Time to recurrence was analysed using the Kaplan-Meier method, log-rank tests and Cox’s proportional hazard models. Result(s)* In total, 126 NSMP-EC were identified in PORTEC-3, the majority were hormone receptor positive (ER n=106/121, 87.6%, PR will be presented at ESGO2021). L1CAM overexpression was observed in 11.2% (n=14/125) and mutations in CTNNB1-exon-3 were identified in 34.3% (n=36/105). Clustering showed that ER-positive NSMP-EC were predominantly endometrioid EC (n=99, 93.4%), low grade (n=88, 83.0%) and L1CAM-negative (n=102, 97.1%) (figure 1). PIK3CA and KRAS mutations were present in 27.3% (n=24) and 19.3% (n=17), respectively. ER-negative NSMP-EC were frequently non-endometrioid (n=11, 73.3%), L1CAM-positive (n=11, 73.3%) and rarely harboured PTEN and CTNNB1 mutations (n=1, 7.1% and 0%, respectively). ER-positivity was associated with lower risk of recurrence (HR 0.32 [95%CI 0.14-0.70]; figure 2A), while L1CAM-overexpression and CTNNB1-exon-3 mutations were not (HR 2.25 [95%CI 0.93-5.43] and HR 1.20 [95%CI 0.57-2.54], respectively). Multivariable analysis confirmed independent favourable prognostic impact of ER-positivity and LVSI. Figure 2B shows impact of LVSI on time to recurrence among patients with ER-positive NSMP-EC. Conclusion* The vast majority of NSMP-HREC are ER-positive (87.6%) and are likely sensitive to hormonal therapy. Other treatment targets might be found in this subgroup too as 27.3% had PIK3CA and 19.3% had KRAS mutations. NSMP-EC with loss of ER-expression were often of non-endometrioid histology and had a high risk of recurrence. Future studies should investigate whether this subgroup would benefit from other systemic therapies.

Introduction/Background* The molecular endometrial cancer (EC) classification has proven prognostic impact. However, patients included in previous studies were not always staged by lymphadenectomy (LND) and often received adjuvant treatment (AT). This may have moderated the prognostic effect of the molecular classification. We evaluated the prognostic significance of the molecular classification in high-grade EC patients staged by LND and those without AT. Methodology Targeted DNA-sequencing for pathogenic POLE-exonuclease domain mutations and immunohistochemistry for mismatch repair (MMR) proteins and p53 expression were performed on 412 high-grade EC from the Danish Gynecological Cancer Database 2005-2012 to classify them as POLE-ultramutated (POLEmut), MMR-deficient (MMRd), p53-mutant (p53abn), or no specific molecular profile (NSMP). Patients with stage IV or residual disease after surgery were excluded. Analyses were performed on patients staged by LND and on patients without AT. Time to recurrence analyses were performed using the Kaplan-Meier method, log-rank test and Cox proportional hazard’s models. Pre-specified multivariate regression analyses were performed including age, ASA class, stage, lymphovascular space invasion and in the LND subgroup a propensity score to correct for confounding by indication. Result(s)* Molecular analysis was successful in 367 EC; 251 patients had undergone LND, see table 1. Median follow-up was 11 years (range 7.5-15.4). Multivariable analysis showed that molecular subgroup was a strong independent prognostic factor for recurrence: p53abn HR 3.88 (95%CI 1.89-7.94, p Among 264 patients without AT, 247 (94%) had stage I-II disease and 17 (6%) stage III. None of the patients with POLEmut EC (n=26, 10%) had a recurrence (figure 1B). Multivariable analysis showed that the significant prognostic impact of molecular subgroup was independent of clinicopathological factors. Conclusion* The molecular EC classification has strong prognostic value, independent of clinicopathological factors, also among patients staged by LND and those without AT. This implies that the unfavourable prognosis of p53abn EC is not caused by undetected lymph node metastasis. POLEmut EC is inherently associated with an excellent prognosis even in the absence of adjuvant treatment.

Approximately 15% of patients with endometrial cancer present with high-risk disease (HREC). Moreover, assessing the extent of lymphovascular space invasion (LVSI) may provide prognostic insight among patients with HREC. The aim of this study was to determine whether the extent of LVSI can serve as a prognostic factor in HREC. All cases of ESMO-ESGO-ESTRO 2016 classified HREC in the Danish Gynecological Cancer Database (DGCD) diagnosed from 2005 to 2012 were reviewed for the presence and extent of LVSI (categorized using a 3-tiered definition). We used the Kaplan-Meier analysis to calculate actuarial survival rates, both adjusted and unadjusted Cox regression analyses were used to calculate the proportional hazard ratio (HR). A total of 376 patients were included in our analysis. Among 305 patients with stage I/II HREC, 8.2% and 6.2% had focal or substantial LVSI, respectively, compared with 12.7% and 38.0% of 71 patients with stage III/IV HREC, respectively. Moreover, the estimated 5-yr recurrence-free survival rate was significantly lower among patients with substantial LVSI compared with patients with no LVSI for both stage I/II (HR: 2.8; P=0.011) and stage III/IV (HR: 2.9; P=0.003) patients. Similarly, overall survival was significantly lower among patients with substantial LVSI for both stage I/II (HR: 3.1; P

B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigated the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells showed presence of activated/memory B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis showed association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence showed L1CAM expression in mature TLS localized in the myometrial wall or at the tumor invasive border, independent of L1CAM expression the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank were evaluated. TLS were found in 19%, predominantly in mismatch-repair deficient and polymerase-epsilon mutant EC. Multivariable Cox regression analysis showed strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker.Statement of significance Tertiary lymphoid structures have a pivotal role in the immune response against endometrial cancer. Presence of mature tertiary lymphoid structures can be easily assessed using L1CAM immunohistochemistry and has independent favorable predictive value for recurrence and endometrial cancer-specific survival.

Aims Human epidermal growth factor receptor 2 (HER2) amplification in endometrial cancer (EC) is almost completely confined to the p53-abnormal (p53abn) molecular subtype and independent of histological subtype. HER2 testing should therefore be molecular subtype-directed. However, the most optimal approach for HER2 testing in EC has not been fully established. Therefore, we developed an EC-specific HER2 immunohistochemistry (IHC) scoring method and evaluated its reproducibility and performance to establish an optimal diagnostic HER2 testing algorithm for p53abn EC. Methods and results HER2 IHC slides of 78 p53abn EC were scored by six gynaecopathologists according to predefined EC-specific IHC scoring criteria. Interobserver agreement was calculated using Fleiss' kappa and the first-order agreement coefficient (AC1). The consensus IHC score was compared with HER2 dual in-situ hybridisation (DISH) results. Sensitivity and specificity were calculated. A substantial interobserver agreement was found using three- or two-tiered scoring [kappa = 0.675, 95% confidence interval (CI) = 0.633-0.717; AC1 = 0.723, 95% CI = 0.643-0.804 and kappa = 0.771, 95% CI = 0.714-0.828; AC1 = 0.774, 95% CI = 0.684-0.865, respectively]. Sensitivity and specificity for the identification of HER2-positive EC was 100 and 97%, respectively, using a HER2 testing algorithm that recommends DISH in all cases with moderate membranous staining in >10% of the tumour (IHC+). Performing DISH on all IHC-2+ and -3+ cases yields a sensitivity and specificity of 100%. Conclusions Our EC-specific HER2 IHC scoring method is reproducible. A screening strategy based on IHC scoring on all cases with subsequent DISH testing on IHC-2+/-3+ cases has perfect test accuracy for identifying HER2-positive EC.

The aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide cohort. From the Danish Gynecological Cancer Database (DGCD) 2005-2012 cohort, we included 425 patients with an original diagnosis of high-grade EC, independent of histologic subtype. Of these, at least one hematoxylin and eosin (H&E)-stained slide from 396 cases (93.2%) was available for review. The histologic subtype was reviewed by specialized gynecopathologists blinded to the original diagnosis and clinical outcome. Interobserver variability between original and revised histologic subtypes was analyzed using simple Kappa statistics. Hazard ratios (HR), recurrence-free survival (RFS), and overall survival were calculated for original and revised subtypes, respectively. Overall histologic subtype agreement was moderate (kappa = 0.42) with the highest agreement for endometrioid-type EC (EEC; 75.5%) and serous-type EC (SEC; 63.8%). For clear cell carcinoma and un-/dedifferentiated EC, agreement was significantly lower: 30.1% and 33.3% respectively. Of the 396 reviewed cases, only two (0.5%) were re-classified as low-grade EEC upon revision. Interestingly, GR3 EEC had better RFS than SEC with stronger significance after revision (HR 2.36 (95% CI 1.43-3.89), p = 0.001), compared to original diagnosis (HR 1.74 (95% CI 1.07-2.81), p = 0.024). In conclusion, this study confirmed that pathology review results in substantial shift in histological subtype in high-grade EC. After review, a stronger prognostic benefit for GR3 EEC as compared to other histological subtypes was observed. This work supports maintaining a low threshold for pathology revision of high-grade EC in clinical practice.

HER2 status has not been investigated in the context of the molecular endometrial cancer (EC) classification. Here, we aimed to determine the clinicopathological features and prognostic significance of the HER2 status in the molecularly classified PORTEC-3 trial population of patients with high-risk EC (HREC). HER2 testing was performed on tumor tissues of 407 molecularly classified HREC. HER2 status was determined by HER2 immunohistochemistry (IHC, all cases) and subsequent HER2 dual in situ hybridization for cases with any (in) complete moderate to strong membranous HER2 IHC expression. The &Chi, 2 test and Spearman&rsquo, s Rho correlation coefficient were used to compare clinicopathological and molecular features. The Kaplan&ndash, Meier method, log-rank test, and Cox proportional hazards models were used for survival analysis. We identified 24 (5.9%) HER2-positive EC of various histological subtypes including serous (n = 9, 37.5%), endometrioid (n = 6, 25.0%), and clear cell (n = 5, 20.8%). HER2 positivity was highly associated with the p53-abnormal subgroup (p53abn, 23/24 cases, p &lt, 0.0001). The correlation between p53abn and the HER2 status (&rho, = 0.438, 0.0001) was significantly stronger (p &lt, 0.0001) than between serous histology and the HER2 status (&rho, = 0.154, p = 0.002). HER2 status did not have independent prognostic value for survival after correction for the molecular classification. Our study strongly suggests that molecular subclass-directed HER2 testing is superior to histotype-directed testing. This insight will be relevant for future trials targeting HER2.

Optimum risk stratification in early-stage endometrial cancer combines clinicopathologic factors and the molecular endometrial cancer classification defined by The Cancer Genome Atlas (TCGA). It is unclear whether analysis of intratumoral immune infiltrate improves this. We developed a machine-learning, image-based algorithm to quantify density of CD8+ and CD103+ immune cells in tumor epithelium and stroma in 695 stage I endometrioid endometrial cancers from the PORTEC-1 and -2 trials. The relationship between immune cell density and clinicopathologic/molecular factors was analyzed by hierarchical clustering and multiple regression. The prognostic value of immune infiltrate by cell type and location was analyzed by univariable and multivariable Cox regression, incorporating the molecular endometrial cancer classification. Tumor-infiltrating immune cell density varied substantially between cases, and more modestly by immune cell type and location. Clustering revealed three groups with high, intermediate, and low densities, with highly significant variation in the proportion of molecular endometrial cancer subgroups between them. Univariable analysis revealed intraepithelial CD8+ cell density as the strongest predictor of endometrial cancer recurrence; multivariable analysis confirmed this was independent of pathologic factors and molecular subgroup. Exploratory analysis suggested this association was not uniform across molecular subgroups, but greatest in tumors with mutant p53 and absent in DNA mismatch repair–deficient cancers. Thus, this work identified that quantification of intraepithelial CD8+ cells improved upon the prognostic utility of the molecular endometrial cancer classification in early-stage endometrial cancer.

PURPOSE The randomized Adjuvant Chemoradiotherapy Versus Radiotherapy Alone in Women With High-Risk Endometrial Cancer (PORTEC-3) trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with high-risk endometrial cancer (EC). Because The Cancer Genome Atlas defined an EC molecular classification with strong prognostic value, we investigated prognosis and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants. METHODS Paraffin-embedded tissues of 423 consenting patients were collected. Immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain were done to classify tumors as p53 abnormal (p53abn), POLE-ultramutated ( POLEmut), MMR-deficient (MMRd), or no specific molecular profile (NSMP). The primary end point was recurrence-free survival (RFS). Kaplan-Meier method, log-rank test, and Cox model were used for analysis. RESULTS Molecular analysis was successful in 410 high-risk EC (97%), identifying the 4 subgroups: p53abn EC (n = 93; 23%), POLEmut (n = 51; 12%), MMRd (n = 137; 33%), and NSMP (n = 129; 32%). Five-year RFS was 48% for patients with p53abn EC, 98% for POLEmut EC, 72% for MMRd EC, and 74% for NSMP EC ( P < .001). The 5-year RFS with CTRT versus RT for p53abn EC was 59% versus 36% ( P = .019); 100% versus 97% for patients with POLEmut EC ( P = .637); 68% versus 76% ( P = .428) for MMRd EC; and 80% versus 68% ( P = .243) for NSMP EC. CONCLUSION Molecular classification has strong prognostic value in high-risk EC, with significantly improved RFS with adjuvant CTRT for p53abn tumors, regardless of histologic type. Patients with POLEmut EC had an excellent RFS in both trial arms. EC molecular classification should be incorporated in the risk stratification of these patients as well as in future trials to target specific subgroups of patients.

Endometrial cancer is a clinically heterogeneous disease and it is becoming increasingly clear that this heterogeneity may be a function of the diversity of the underlying molecular alterations. Recent large-scale genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes, with well-described underlying genomic aberrations. These subtypes can be reliably delineated and carry significant prognostic as well as predictive information; embracing and incorporating them into clinical practice is thus attractive. The road towards the integration of molecular features into current classification systems is not without obstacles. Collaborative studies engaging research teams from across the world are working to define pragmatic assays, improve risk stratification systems by combining molecular features and traditional clinicopathological parameters, and determine how molecular classification can be optimally utilized to direct patient care. Pathologists and clinicians caring for women with endometrial cancer need to engage with and understand the possibilities and limitations of this new approach, because integration of molecular classification of endometrial cancers is anticipated to become an essential part of gynaecological pathology practice. This review will describe the challenges in current systems of endometrial carcinoma classification, the evolution of new molecular technologies that define prognostically distinct molecular subtypes, and potential applications of molecular classification as a step towards precision medicine and refining care for individuals with the most common gynaecological cancer in the developed world. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Cutaneous angiosarcoma can be challenging to diagnose particularly when poorly vasoformative and studied on biopsies. We report a case of a cutaneous angiosarcoma with strong positivity for tyrosinase, the first to our knowledge, initially misdiagnosed as melanoma. We subsequently evaluated the reactivity of panmelanocytic cocktail (tyrosinase, HMB-45 and Melan-A), SOX10, tyrosinase and MITF in a large tissue microarray (TMA) of angiosarcoma. The TMA included 142 cases of angiosarcomas (29 cutaneous, 22 primary breast, 41 post-radiation breast, 15 visceral, 26 deep soft tissue and bone, 5 chronic lymphedema-associated and 4 angiosarcomas arising in other sarcomas). Immunohistochemical studies were performed with anti-panmelanocytic cocktail, anti-SOX10, anti-MITF and anti-tyrosinase antibodies. TMA staining results were scored on intensity and percentage of tumoral labeling. Aside from the index case, no cases (0 of 133) showed positivity for tyrosinase including 28 cutaneous angiosarcomas. One breast angiosarcoma (1 of 131) was positive for MITF. All cases were negative for SOX10 and panmelanocytic cocktail (0 of 132). Angiosarcomas can rarely be positive for tyrosinase and MITF. Pathologists should be cognizant of these rare exceptions to prevent confusion with melanoma. Additional immunohistochemical markers for vascular and melanocytic differentiation, thorough histological examination for vasoformative and in situ areas as well as clinical impression are helpful in these exceptionally problematic cases.

Background The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with stage I-III endometrial cancer with high-risk features (HREC). Since the TCGA defined 4 molecular subgroups of EC with strong prognostic value, we investigated outcomes and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants. Methods Paraffin-embedded tissues of 423 consenting patients (64% of 660) were collected. Immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE pathogenic exonuclease domain mutations were done to classify tumours as p53 mutant staining (p53abn), POLE ultramutated (POLEmut), MMR deficient (MMRd), or no specific molecular profile (NSMP). The Kaplan-Meier method, log-rank test and Cox model were used for analysis. Results Molecular analysis was successful in 410 HREC (97%), identifying the four subgroups; p53abn (n = 92, 22%), POLEmut (n = 52, 13%), MMRd (n = 137, 33%) and NSMP (n = 129, 32%). Five-year recurrence free survival (RFS) was 50% for patients with p53abn HREC, 98% for POLEmut, 74% for MMRd and 76% for NSMP (p Table: LBA63 . Recurrence-free survival by molecular subgroup Events 5-year estimate % HR (95% CI) P value of HR p53abn EC RT 28 37,2 1 CTRT 20 61,1 0,50 (0,28-0,88) 0,017 POLEmut EC RT 1 96,6 1 CTRT 0 100 0,02 ( 104) 0,632 MMRd EC RT 17 75,8 1 CTRT 18 72,4 1,15 (0,59-2,22) 0,687 NSMP EC RT 19 68,9 1 CTRT 17 81,2 0,71 (0,37-1,37) 0,311 Conclusions Molecular EC classification has a strong prognostic value in HREC and better identifies those who benefit from adjuvant CTRT than clinicopathological factors. Patients with p53abn HREC had significantly improved RFS with adjuvant CTRT, while those with MMRd did not seem to benefit from chemotherapy. Patients with POLEmut HREC had an excellent RFS in both arms. Future trials should incorporate the molecular classification and target specific subgroups. Clinical trial identification NCT00411138. Legal entity responsible for the study Leiden University Medical Center. Funding Koningin Wilhelmina Fonds voor de Nederlandse Kankerbestrijding (KWF). Disclosure A. Leary: Travel / Accommodation / Expenses, Officer / Board of Directors: AZ; Officer / Board of Directors: Tesaro; Officer / Board of Directors: Clovis; Officer / Board of Directors: MSD; Officer / Board of Directors: Grisdstone; Officer / Board of Directors: Seattle Genetics; Officer / Board of Directors: Gamamabs; Officer / Board of Directors: Biocad; Travel / Accommodation / Expenses: Roche . H.W. Nijman: Leadership role, Founder: SME Vicinivax; Advisory / Consultancy: Aduro; Advisory / Consultancy: TRON ; Advisory / Consultancy: Merck. All other authors have declared no conflicts of interest.

In Cuba, exist a historiographical vacuum respect to the rural schools of La Havana between 1936 and 1952, for which it outlines as problem of investigation the manifestation of the material conditions and it humanize of those schools in the solution of the educational problems of the Cuban teaching during those years. The general objective of this article is to characterize the material and psychological conditions in those who the teachers must develop your classes. They were employed methods of the theoretical and empiric level respectively, just as historical, logical, analytic, synthetic, and inductive-deductive and the documentary analysis. Between the main results, it finds that the plains of study and program of the rural schools of La Havana favored the solution of one of the main educational existent problems in the teaching, however several of the regulations that these outlined did not manage to make concrete in all your amplitude due to the inattention of the republican governments. RESUMO. Em Cuba há um vazio historiográfico no que diz respeito às escolas rurais em Havana de 1936 a 1952, se caracterizando como problema de pesquisa a manifestação do condições materiais e humanas dessas escolas na resolução de problemas educacionais da educação cubana durante esses anos. Nesta pesquisa científica é apresentado como objetivo principal caracterizar as condições materiais e psicológicas em que os professores desenvolvem as suas aulas. Foram utilizados métodos de nível teórico e empírico, respectivamente, tais como: histórico e lógico, analítico-sintético, indutivo-dedutivo e estudo documental. Entre os principais resultados foi constatado que os currículos e programas de escolas rurais em Havana apresentam soluções para alguns problemas educacionais existentes no ensino ofertado por essas instituições; no entanto, vários dos regulamentos que essas escolas implantaram não foram capazes de materializar todo a amplitude do ensino devido à negligência dos governos republicanos, embora as suas contribuições para a pedagogia e didática tenham sido significativas. As escolas rurais de Havana: um problema sem resolver na República Neocolonial de 1936 a 1952 Em Cuba há um vazio historiográfico no que diz respeito às escolas rurais em Havana de 1936 a 1952, se caracterizando como problema de pesquisa a manifestação de condições materiais e humanas dessas escolas na resolução de problemas educacionais da educação cubana durante esses anos. Nesta pesquisa científica é apresentado como objetivo principal caracterizar as condições materiais e psicológicas em que os professores desenvolvem as suas aulas. Foram utilizados métodos de nível teórico e empírico, respectivamente, tais como: histórico e lógico, analítico-sintético, indutivo-dedutivo e estudo documental. Entre os principais resultados foi constatado que os currículos e programas de escolas rurais em Havana apresentam soluções para alguns problemas educacionais existentes no ensino ofertado por essas instituições; no entanto, vários dos regulamentos que essas escolas implantaram não foram capazes de materializar toda a amplitude do ensino devido à negligência dos governos republicanos, embora as suas contribuições para a pedagogia e didática tenham sido significativas. Palavras-chave: Escolas Rurais, Professores Rurais, Programas, Práticas Educacionais. The rural schools of Havana: a problem without turns into the Neo-colonial republic between 1936 and 1952 ABSTRACT. In Cuba, exist a historiographical vacuum respect to the rural schools of La Havana between 1936 and 1952, for which it outlines as problem of investigation the manifestation of the material conditions and it humanize of those schools in the solution of the educational problems of the Cuban teaching during those years. The general objective of this article is to characterize the material and psychological conditions in those who the teachers must develop your classes. They were employed methods of the theoretical and empiric level respectively, just as historical, logical, analytic, synthetic, and inductive-deductive and the documentary analysis. Between the main results, it finds that the plains of study and program of the rural schools of La Havana favored the solution of one of the main educational existent problems in the teaching, however several of the regulations that these outlined did not manage to make concrete in all your amplitude due to the inattention of the republican governments. Keywords: Rural Schools, Rural Teachers, Program, Practical Educational. Las escuelas rurales de La Habana: un problema sin resolver en la República Neocolonial entre 1936 y 1952 RESUMEN. En Cuba existe un vacío historiográfico respecto a las escuelas rurales de La Habana entre 1936 y 1952, por lo que se plantea como problema de investigación la manifestación de las condiciones materiales y humanas de esas escuelas en la solución de los problemas educativos de la enseñanza cubana durante esos años. El objetivo general de este artículo es caracterizar las condiciones materiales y psicológicas en las que los maestros debían desarrollar sus clases. Fueron empleados métodos del nivel teórico y empírico respectivamente, tales como: histórico-lógico, analítico-sintético, inductivo-deductivo y el análisis documental. Entre los principales resultados se encuentra que los planes de estudio y programas de las escuelas rurales de La Habana favorecieron la solución de algunos de los principales problemas educativos existentes en la enseñanza, sin embargo varias de las regulaciones que estos planteaban no alcanzaron a concretarse en toda su amplitud debido a la desatención de los gobiernos republicanos. Palabras clave: Escuelas Rurales, Maestros Rurales, Programas, Prácticas Educativas.

La agresividad en las aulas manifestados por los estudiantes es un problema social, educativo y humano, que está causando malestar en los docentes, quienes tienen que lidiar con este problema diariamente, los cuales causan disrupción en las aulas, y perjudican el normal proceso de enseñanza aprendizaje, generando malestar en la comunidad educativa, asimismo, ocasionan que las relaciones interpersonales se vean resquebrajadas cada día, todo lo antes mencionado nos motivó a investigar este fenómeno, es una investigación descriptiva explicativa, cuyo objetivo principal es analizar la agresividad y su influencia en la convivencia en el aula, en los estudiantes de cuarto grado de educación primaria de la I.E. Gran Unidad Escolar Mariano Melgar. Arequipa, 2017. La población comprende a 42 estudiantes, asimismo, para recoger los datos se aplicó la escala de agresividad EGA la cual midió los niveles de agresividad y la escala de convivencia en el aula ECA la que midió la convivencia en el aula. Sin embargo, es necesario resaltar que según los resultados obtenidos los niveles de agresividad son regulares con el 67%, también se observa regular convivencia en el aula con un 95%. Se concluye que la agresividad influye en la convivencia en el aula, afecta las relaciones sociales, el proceso de enseñanza aprendizaje, el rendimiento académico y esto genera desmotivación, estrés en los estudiantes. Tesis

El presente informe de investigación titulado: Intervención de enfermería en la Promoción y Prevención del dengue con el personal Militar que labora en el Grupo Aéreo No7 FAP PIURA, está constituido en diversos capítulos y subtítulos teniendo en cuenta las acciones preventivas promocionales que desarrolla el profesional de enfermería ya que son de crucial importancia para el control del vector. Ya que en sus funciones está considerada la de Educar al Paciente, familia y comunidad y a la vez participar activamente junto al equipo multidisciplinario y con la Población Militar FAP en la erradicación del vector enfatizando en la educación para la salud, que lleva a las personas a actuar de determinada manera frente a su salud. Estas acciones preventivas y promocionales están sujetas a lograr el control del DENGUE y proteger la salud y prolongar la vida de la Población Militar que labora en el Grupo Aéreo No7 FAP-PIURA. Es de vital importancia que la enfermera realice acciones con la población FAP de manera objetiva y planificada, para obtener óptimos resultados. En este caso el dengue es una patología que puede prevenirse, con una correcta educación para la salud, Según el último Boletín epidemiológico de MINSA hay 6,362 casos de dengue a nivel nacional y Piura presenta la mayor cantidad de incidencia de dengue debido a las intensas lluvias e inundaciones. (EL TIEMPO, 2017) Este año MINSA declaro ocho regiones en emergencia sanitaria.- Piura, Tumbes, Lambayeque, Cajamarca, La Libertad, Ancash, Lima e lea y registra 5,289 casos de dengue a nivel nacional. (EL TIEMPO, 2017) Siendo Piura una ciudad ubicada en la región noroeste del país. Densamente poblado, con un clima cálido durante todo el año con una temperatura máxima de 40 o C, se convierte en una ciudad con factores ambientales para la incubación del virus del dengue. Trabajo academico