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Short-chain fatty acids (SCFAs) can have pro- or anti-inflammatory properties, but their relationship with multiple sclerosis (MS) relapses during pregnancy remains unknown. This study aimed to explore SCFA profiles in MS patients during pregnancy and to assess their association with the appearance of relapses during pregnancy and postpartum.We prospectively included 53 pregnant MS patients and 21 healthy control women. Patients were evaluated during pregnancy and puerperium. SCFAs were measured by liquid chromatography-mass spectrometry.Sixteen patients (32%) had relapses during pregnancy or puerperium, and 37 (68%) did not. All MS patients showed significant increases in acetate levels during pregnancy and the postpartum period compared to non-MS women. However, propionate and butyrate values were associated with disease activity. Their values were higher in nonrelapsing patients and remained similar to the control group in relapsing patients. The variable that best identified active patients was the propionate/acetate ratio. Ratios of0.36 during the first trimester were associated with higher inflammatory activity (odds ratio = 165, 95% confidence interval = 10.2-239.4, p 0.01). Most nonrelapsing patients showed values of0.36, which were similar to those in healthy pregnant women.Low propionate/acetate ratio values during the first trimester of gestation identified MS patients at risk of relapses during pregnancy and the postpartum period.

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p

Background:Prognostic markers are needed to guide multiple sclerosis (MS) management in the context of large availability of disease-modifying drugs (DMDs).Objective:To investigate the role of cerebrospinal fluid (CSF) markers to inform long-term MS outcomes.Methods:Demographic features, IgM index, oligoclonal IgM bands (OCMB), lipid-specific OCMB, CSF neurofilament light chain protein levels, expanded disability status scale (EDSS), relapses and DMD use over the study period and peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIPL) thicknesses in non-optic neuritis eyes (end of follow-up) were collected from relapsing MS (RMS) patients with CSF obtained ⩽2 years after MS onset prospectively followed at the Hospital Clinic of Barcelona. We assessed associations between CSF markers and MS outcomes using multivariable models.Results:A total of 89 patients (71 females; median 32.9 years of age) followed over a median of 9.6 years were included. OCMB were associated with a 33% increase in the annualized relapse rate (ARR; p = 0.06), higher odds for high-efficacy DMDs use (OR = 4.8; 95% CI = (1.5, 16.1)), thinner pRNFL (β = −4.4; 95% CI = (−8.6, −0.2)) and GCIPL (β = −2.9; 95% CI = (−5.9, +0.05)), and higher rates to EDSS ⩾ 3.0 (HR = 4.4; 95% CI = (1.6, 11.8)) and EDSS ⩾ 4.0 (HR = 5.4; 95% CI = (1.1, 27.1)). No overall associations were found for other CSF markers.Conclusion:The presence of OCMB was associated with unfavorable long-term outcomes. OCMB should be determined in RMS to inform long-term prognosis.

Dentro de la literatura sobre asociacionismo municipal se ha prestado atención a los elementos que favorecen e inhiben la conformación de esta figura. El objetivo de este estudio es evaluar las condiciones que presentan cinco municipios mexicanos para su posible asociación, ubicados en los Estados de Quintana Roo y Campeche. Para ello, se consideraron variables geográficas, políticas, sociales, económicas y jurídicas. Lo que se pretende con este asociativismo es una reterritorialización, es decir, organizar un trabajo en común y crear estructuras cooperativas que articulen la dinámica socioeconómica y política de una sociedad que se encuentra en un espacio bajo indefinición jurisdiccional.

ImportanceThe value of serum neurofilament light chain (sNfL) levels for predicting long-term disability in patients with multiple sclerosis (MS) remains controversial.ObjectiveTo assess whether high sNfL values are associated with disability worsening in patients who underwent their first demyelinating MS event.Design, Setting, and ParticipantsThis multicenter cohort study included patients who underwent their first demyelinating event suggestive of MS at Hospital Universitario Ramón y Cajal (development cohort; June 1, 1994, to September 31, 2021, with follow-up until August 31, 2022) and 8 Spanish hospitals (validation cohort; October 1, 1995, to August 4, 2020, with follow-up until August 16, 2022).ExposuresClinical evaluations at least every 6 months.Main Outcomes and MeasuresThe main outcomes were 6-month confirmed disability worsening (CDW) and an Expanded Disability Status Scale (EDSS) score of 3. Levels of sNfL were measured in blood samples obtained within 12 months after disease onset using a single molecule array kit. The cutoffs used were sNfL level of 10 pg/mL and a standardized score (z score) of 1.5. Multivariable Cox proportional hazards regression models were used to evaluate outcomes.ResultsOf the 578 patients included in the study, 327 were in the development cohort (median age at sNfL analysis, 34.1 years [IQR, 27.2-42.7 years]; 226 female [69.1%]) and 251 patients were in the validation cohort (median age at sNfL analysis, 33.3 years [IQR, 27.4-41.5 years]; 184 female [73.3%]). The median follow-up was 7.10 years (IQR, 4.18-10.0 years). Levels of sNfL greater than 10 pg/mL were independently associated with higher risk of 6-month CDW and an EDSS of 3 in the development cohort (6-month CDW: hazard ratio [HR], 2.39; 95% CI, 1.39-4.12; P = .002; EDSS of 3: HR, 4.12; 95% CI, 2.18-7.77; P P = .02; EDSS of 3: HR, 2.03; 95% CI, 1.23-3.33; P = .005). Highly effective disease-modifying treatments were associated with lower risks of 6-month CDW and an EDSS of 3 in patients with high baseline sNfL values.Conclusions and RelevanceThis cohort study found that high sNfL values obtained within the first year of disease were associated with long-term disability worsening in MS, suggesting that sNfL level measurement may help identify optimal candidates for highly effective disease-modifying treatments.

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS., This work was supported by grants FIS-PI15/00513, FIS-PI18/00572 and RD16/0015/0001 from the Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación, Spain and FEDER: "Una manera de hacer Europa".

Immunosuppression (IS) and autoimmune disease (AD) are prevalent in patients with severe coronavirus disease 2019 (COVID-19), but their impact on its clinical course is unknown. We investigated relationships between IS, AD, and outcomes in patients hospitalized with COVID-19. Data on consecutive admissions for COVID-19 were extracted retrospectively from medical records. Patients were assigned to one of four cohorts, according to whether or not they had an AD (AD and NAD) or were immunosuppressed (IS and NIS). The primary endpoint was development of severe acute respiratory distress syndrome (ARDS); secondary endpoints included death, and a composite of mechanical ventilation (MV) or death. A total of 789 patients were included: 569 (72.1%) male, 76 (9.6%) with an AD, and 63 (8.0%) with IS. Relative to the NIS-NAD cohort, patients in the IS-AD cohort had a significantly reduced risk of severe ARDS (adjusted hazard ratio [aHR] 0.42; 95% confidence interval [CI] 0.23–0.80; p = 0.008). No significant relationships between IS or AD status and either death or the composite of MV and death were identified, although a trend towards higher mortality was identified in the IS-NAD cohort (aHR vs NIS-NAD 1.71; 95% CI 0.94–3.12; p = 0.081). Patients in this cohort also had higher median serum levels of interleukin-6 compared with IS-AD patients (98.2 vs 21.6 pg/mL; p = 0.0328) and NIS-NAD patients (29.1 pg/mL; p = 0.0057). In conclusion, among patients hospitalized with COVID-19, those receiving immunosuppressive treatment for an AD may have a reduced risk of developing severe ARDS. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-020-00927-y.

Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. We evaluated the mortality, the risk of need for mechanical ventilation (MV), or death and the risk of developing a severe acute respiratory distress syndrome (ARDS) between high (HD) and standard doses (SD) among patients with a severe COVID-19. All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an ARDS. Patients were allocated to the HD (≥ 250 mg/day of methylprednisolone) of corticosteroids or the SD (≤ 1.5 mg/kg/day of methylprednisolone) at discretion of treating physician. Five hundred seventy-three patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54–73) years. In the HD group, a worse baseline respiratory situation was observed and male gender, older age, and comorbidities were significantly more common. After adjusting by baseline characteristics, HDs were associated with a higher mortality than SD (adjusted OR 2.46, 95% CI 1.59–3.81, p

A woman with mild coronavirus disease 2019 developed cervical adenopathy, being diagnosed of Epstein-Barr virus infectious mononucleosis. We performed fine needle aspiration, and demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in lymph nodes even in mild disease along with a strong expansion of terminally differentiated effector memory CD4+ T cells, a cell population that is practically absent in lymph nodes.

INTRODUCTIONDespite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients.METHODSAll consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress syndrome (ARDS). Patients were allocated to the high doses (HD, ≥250mg/day of methylprednisolone) of corticosteroids or the standard doses (SD, ≤1.5mg/kg/day of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death and the risk of developing a severe ARDS.RESULTS573 patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54–73) years. In HD cohort, a worse baseline respiratory situation was observed and male sex, older age and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58 – 3.83, pCONCLUSIONOur real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.SUMMARYIn patients with severe COVID-19, high doses of corticosteroids are associated with a higher mortality and risk of need for mechanical ventilation or death compared to standard doses. This deleterious effect is mainly observed in the elderly.

Resumen: Desde la década de 1950 se llevó a cabo en México una política colonizadora con la idea de aprovechar los “espacios vacíos” ocupados por la selva, en zonas delicadas como son las fronterizas, y destinarlos a actividades productivas como lo son las agropecuarias. La apropiación que realizaron los pobladores del espacio y el uso del suelo son procesos socioeconómicos complementarios y complejos, ya que interactúan situaciones de orden natural y actividades antropogénicas; en consecuencia, su análisis debe considerar, entre otros elementos, a la población y la colonización que realizaron del área. El objetivo de este artículo es exponer cuáles fueron las motivaciones y circunstancias del proceso migratorio, así como el momento en el que la zona objeto de estudio, localizada en la Península de Yucatán, México, experimentó su poblamiento. Para ello, se llevó a cabo la revisión de fuentes bibliográficas, institucionales y hemerográficas, pero, sobre todo, este artículo es fruto del trabajo de campo realizado por medio de encuestas y de la observación no participante, con uso de cámara fotográfica. Palabras clave: Campeche; conflicto limítrofe; Quintana Roo; indígenas. Abstract: Since the 1950s a colonizing policy was carried out in Mexico with the idea of taking advantage of the "empty spaces" occupied by the jungle, in delicate areas such as border areas, and allocating them to productive activities such as agriculture. The appropriation by the inhabitants of space and land use are complementary and complex socio-economic processes, since natural situations and anthropogenic activities interact; consequently, their analysis should consider, among other elements, the population and colonization they performed in the area. The objective of this article is to expose what were the motivations and circumstances of the migratory process, as well as the moment in which the area under study, located in the Yucatan Peninsula, Mexico, experienced its settlement. To this end, the review of bibliographic, institutional and hemerographic sources was carried out, but, above all, this article is the result of the field work carried out through surveys and non-participant observation, with the use of a photographic camera. Key words: Campeche; conflict bordering; Quintana Roo; natives.

Background: The influence of vocation on success can be studied through various surveys, but a model is needed that will validate the results of such surveys with a high probability of accurately representing the reality under study. Bayesian networks meet this requirement Purpose: Students who enroll on an engineering degree may have to choose engineering disciplines that differ from their initial choice. In some cases, these differences can undermine their vocational commitment and leave them with the feeling that their final choice was mistaken. This study is intended to gauge engineering student perceptions of success in terms of vocation and to remedy weaknesses that may discernible in their attitudes. Method: Bayesian networks, by choosing a variable, proper graphs, probabilistic calculation and survey validations with the ROC curve (Receiver Operating Characteristic) can identify variable-dependent survey results and filter them accordingly. Results: Issues relating to professional expectations and learning have more influence on students whether they are or are not in the specific field of engineering that reflected their vocation. Success rates increase considerably when students perceive variables such as "find useful work", "find a job easily" or "enjoy learning" in a positive light. Conclusions: What helps students to feel that they are not wrong is to think that they will find employment and that their jobs will make them feel useful. It is therefore essential to talk about professional life from the very first year through to graduation and students should do so believing fully in their choice of degree.

Although the etiology of multiple sclerosis (MS) is still unknown, it is commonly accepted that environmental factors could contribute to the disease. The objective of this study was to analyze the humoral response to Epstein-Barr virus, human herpesvirus 6A/B and cytomegalovirus, and the levels of 25-hydroxyvitamin D (25(OH)D) and the three main short-chain fatty acids (SCFA), propionate (PA), butyrate (BA) and acetate (AA), in MS patients and healthy controls (HC) to understand how they could contribute to the pathogenesis of the disease. With this purpose, we analyzed the correlations among them and with different clinical variables and a wide panel of cell subsets. We found statistically significant differences for most of the environmental factors analyzed when we compared MS patients and HC, supporting their possible involvement in the disease. The strongest correlations with the clinical variables and the cell subsets analyzed were found for 25(OH)D and SCFAs levels. A correlation was also found between 25(OH)D and PA/AA ratio, and the interaction between these factors negatively correlated with interleukin 17 (IL-17)-producing CD4+ and CD8+ T cells in untreated MS patients. Therapies that simultaneously increase vitamin D levels and modify the proportion of SCFA could be evaluated in the future.

ObjectiveTo analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS).MethodsIn this multicenter prospective study including 53 patients with PPMS who initiated ocrelizumab treatment, we determined effector, memory, and regulatory cells by flow cytometry at baseline and after 6 months of therapy. Wilcoxon matched paired tests were used to assess differences between baseline and 6 months' results. p Values were corrected using the Bonferroni test.ResultsOcrelizumab reduced the numbers of naive and memory B cells (p < 0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNFα) (p < 0.0001 in all cases). By contrast, the proportions of plasmablasts and B cells producing GM-CSF and TNFα increased significantly, suggesting the need for treatment continuation. We also observed a decrease in CD20+ T-cell numbers (p < 0.0001) and percentages (p < 0.0001), and a clear remodeling of the T-cell compartment characterized by relative increases of the naive/effector ratios in CD4+ (p = 0.002) and CD8+ (p = 0.002) T cells and relative decreases of CD4+ (p = 0.03) and CD8+ (p = 0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p = 0.002), but no changes were observed in those producing inflammatory cytokines. The immunologic variations were associated with a reduction of serum neurofilament light chain (sNfL) levels (p = 0.008). The reduction was observed in patients with Gd-enhanced lesions at baseline and in Gd− patients with baseline sNfL >10 pg/mL.ConclusionsIn PPMS, effector B-cell depletion changed T-cell response toward a low inflammatory profile, resulting in decreased sNfL levels.

Background Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. Objectives To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. Methods Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. Results Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e–4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e–4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r = − 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001). Conclusions Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

Resumen . Este articulo tiene como objetivo general proponer un modelo de asociacion municipal que pueda favorecer un desarrollo sostenible de la region objeto de estudio, la cual se encuentra inserta en una disputa territorial en la Peninsula de Yucatan, Mexico. Para la realizacion de esta investigacion se llevo a cabo un metodo hipotetico-deductivo, fundamentalmente cualitativo, analizando las corrientes teoricas en torno a la gobernanza, asi como las tendencias mas sobresalientes en el debate actual sobre el modelo de gestion consistente en la asociacion entre municipios. Se hace uso del metodo predictivo, al disenar un modelo de asociacion municipal apropiado a la zona objeto de estudio, con el cual se preve mitigar la problematica que se da en la actualidad. Asi mismo, se da respuesta a la cuestion de que es lo que motiva el conflicto territorial en el caso de estudio y se concluye con la propuesta de creacion de un organismo publico descentralizado que haga las veces de una agencia ambiental intermunicipal. Palabras clave : agente tecnico local, agencia ambiental, junta intermunicipal, subsidiariedad, cooperacion. Abstract . This article has as a general objective to propose a model of municipal association that can favour a sustainable development of the region under study, which is inserted in a territorial dispute in the Yucatan Peninsula, Mexico. In order to carry out this research, a hypothetical-deductive method, fundamentally qualitative, was carried out, analysing the theoretical currents around governance, as well as the most outstanding trends in the current debate on the management model consisting of the association between municipalities. The predictive method is used to design a model of municipal association appropriate to the area under study, which is expected to mitigate the current problem. Likewise, the question of what motivates the territorial conflict in the case study is answered and concludes with the proposal to create a decentralized public body that acts as an intermunicipality environmental agency. Key words : local technical agent, environmental agency, intermunicipal board, subsidiarity, cooperation .

Objective To explore the serum cytokine profile associated with disease activity during pregnancy and postpartum in MS, and to assess any potential biomarkers predicting the occurrence of relapses during this period. Methods We included 53 MS pregnant women recruited between 2007 and 2018. Interferon-gamma, Tumor necrosis factor-alpha, interleukin-17, granulocyte/macrophage-colony stimulating factor, Activin-A, interleukin-10, and programmed-death-ligand-1 (PD-L1) were measured quarterly in serum by ELISA. Results Seventeen patients (32%) experienced relapses during pregnancy or puerperium and 37(68%) did not. We did not found differences in clinical characteristics or treatment status between the two groups. However, relapsing patients showed at the first trimester of pregnancy considerably lower levels of serum Activin-A (336.4 pg/dl [289.6–491.7], median [IQR] vs. 760.0 pg/dl [493.2–1108.0],p = .003), which correlated positively with serum PD-L1 (r = 0.53,p = .0005) and IL-10 (r = 0.43,p = .004) values. Activin-A levels lower than 515 pg/ml at the first trimester identified patients with high probability of relapsing during pregnancy and postpartum (OR = 13.75, CI: 2.5–76.8, p = .001). Conclusions MS patients with no relapses during pregnancy and puerperium showed an early triggering of a tolerogenic innate immune response evidenced by high serum Activin-A concentrations during the first trimester of pregnancy. Thus, serum Activin-A can be a useful biomarker to predict clinical activity during this period.

Resumen Este artículo revisa el marco histórico de la explotación forestal y de la pérdida de la riqueza maderera y de la cobertura forestal en relación con el poblamiento rural propiciado por algunas políticas de colonización en la Península de Yucatán desde la década de 1950, como el Programa Nacional de Desmontes, o proyectos económicos como el arrocero, el azucarero y el ganadero. También se analizan los esfuerzos que actualmente se están llevando a cabo para mitigar e, incluso, revertir la deforestación con base en políticas públicas internacionales que han sido asumidas por las autoridades mexicanas. Este trabajo cualitativo es producto de la revisión de literatura académica e institucional. Permite advertir cómo el paso de la explotación forestal extractiva a la sustentable aún se sitúa en un contexto en el que la geopolítica es determinante. Abstract This article reviews the historical framework of logging and the loss of timber wealth and forest cover in relation to a rural settlement process caused by some colonization policies in the Yucatan Peninsula since the 1950s, such as the National Felling Program and some rice, sugar and livestock production projects. Efforts being made to mitigate and even reverse deforestation following international public policies that have been adopted by Mexican authorities are also discussed. This qualitative paper derives from a review of academic and institutional literature. It is concluded that the transition from extractive to sustainable logging is still placed in a context in which geopolitics is a determining factor. Resumo Este artigo revê o marco histórico da exploração florestal e da perda de riqueza madeireira e da cobertura florestal em relação à população rural causada por algumas políticas de colonização na Península de Iucatã desde a década de 1950, como o Programa Nacional de Desmantelamento, ou projetos econômicos como o arrozeiro, o açucareiro e o pecuário. Também se analisaram os esforços que atualmente são realizados para mitigar e até reverter o desmatamento com base em políticas públicas internacionais que têm sido empreendidas pelas autoridades mexicanas. Este trabalho qualitativo é o produto da revisão da literatura acadêmica e institucional. Permite observar como o caminho da exploração florestal extrativa em direção à sustentabilidade ainda está em um contexto em que a geopolítica é decisiva.

Fundamentos: El término Patient Reported Outcomes (PRO) es definido como el resultado de la evaluación de un medicamento por el paciente y basada en su percepción de la enfermedad y su(s) tratamientos(s). El objetivo del estudio es determinar la utilización de PRO y compararla con otros tipos de variables de la eficacia contenidas en las fichas técnicas (FT) de medicamentos. Métodos: Revisión y análisis descriptivo de las variables de eficacia utilizadas en los ensayos clínicos de principios activos aprobados en España durante el período 2000-2012, descritas en las fichas técnicas clasificándolas en las siguientes categorías: PRO, resultados informados por el clínico (CRO) y resultados finales basados en pruebas de laboratorio (ML). Para las comparaciones se realizaron la prueba chi2 o la prueba exacta de Fisher, y se calcularon odd ratios para valorar la intensidad de la asociación. Resultados: De las 330 FT estudiadas se incluyeron PROs en 65 (19,7%), los CRO en 188 (57%) y los ML en 128 (38,7%). Los PRO se utilizaron como único resultado final de eficacia en 6 medicamentos. Se observó una tendencia creciente de la significación estadística en la utilización de PRO a lo largo del tiempo estudiado (R2=0,525; p=0,079). Conclusiones: La frecuencia de utilización de PRO en FT es claramente inferior a la de las otras medidas de la eficacia, siendo la diferencia significativamente mayor en el caso de su inclusión como variable única final. La utilización de PROs fue más frecuente en medicamentos del sistema nervioso, agentes inmunomoduladores, sistema respiratorio y sistema musculoesquelético.

This paper offers a survey of a series of fundamental notions on the philosophy of Karl Popper that enable to understand the quid and the status of metaphysics towards the critiques of the Vienna Circle in a post-kantian epoch. Elemental concerns of the philosophy of science of Popper are traced out, highlighting the importance of kantian influence, the reformulation of critique as the rational process of testing and finding errors, the grievance of theories as interpretations of facts, the modification of traditional methodology, the dimenssions of compatibility and validity regarding scientific knowledge in is empirical or speculative flavors, among others. At the same time, it is pointed out a series of throughly philosophical errors, particularly regarding the inconcruity of vage and neglected use of language that Popper, formerly severe on this topic, employed. The paper concludes with an analysis of popperian metaphysics understood as a rational knowledge of a non-verifiable, non-refutable, yet argumentable type which belongs to the sphere of science, though in a special and subordinate way: as the methodology of the unverifiable.

The spider principle is used for establishing a formula for a finite quadratic sequence which determines the multiplicity sequences of all the sprouts which are founded upon the given finite quadratic sequence. This formula is basic for the theories of curvettes and dicriticals.

Background Three-dimensional (3D) printing is relatively a new technology with clinical applications, which enable us to create rapid accurate prototype of the selected anatomic region, making it possible to plan complex surgery and pre-bend hardware for individual surgical cases. This study aimed to express our experience with the use of medical rapid prototype (MRP) of the maxillofacial region created by desktop 3D printer and its application in maxillofacial reconstructive surgeries. Material and methods Three patients with benign mandible tumors were included in this study after obtaining informed consent. All patient's maxillofacial CT scan data was processed by segmentation and isolation software and mandible MRP was printed using our desktop 3D printer. These models were used for preoperative surgical planning and prebending of the reconstruction plate. Conclusions MRP created by desktop 3D printer is a cost-efficient, quick and easily produced appliance for the planning of reconstructive surgery. It can contribute in patient orientation and helping them in a better understanding of their condition and proposed surgical treatment. It helps surgeons for pre-operative planning in the resection or reconstruction cases and represent an excellent tool in academic setting for residents training. The pre-bended reconstruction plate based on MRP, resulted in decreased surgery time, cost and anesthesia risks on the patients. Key words:3D printing, medical modeling, rapid prototype, mandibular reconstruction, ameloblastoma.

The topological theory of dicritical divisors is algebracized which makes it valid for nonzero characteristic as well as mixed characteristic.

Let R be either the Grothendieck semiring (semigroup with multiplication) of complex quasi-projective varieties, or the Grothendieck ring of these varieties, or the Grothendieck ring localized by the class \L of the complex affine line. We define a power structure over these (semi)rings. This means that, for a power series A(t)=1+∑i=1∞[Ai]ti with the coefficients [Ai] from R and for [M]∈R, there is defined a series (A(t))[M], also with coefficients from R, so that all the usual properties of the exponential function hold. In the particular case A(t)=(1−t)−1, the series (A(t))[M] is the motivic zeta function introduced by M. Kapranov. As an application we express the generating function of the Hilbert scheme of points, 0-dimensional subschemes, on a surface as an exponential of the surface.

In this paper we study some properties of the class of nu-quasi-ordinary hypersurface singularities. They are defined by a very mild condition on its (projected) Newton polygon. We associate with them a Newton tree and characterize quasi-ordinary hypersurface singularities among nu-quasi-ordinary hypersurface singularities in terms of their Newton tree. A formula to compute the discriminant of a quasi-ordinary Weierstrass polynomial in terms of the decorations of its Newton tree is given. This allows to compute the discriminant avoiding the use of determinants and even for non Weierstrass prepared polynomials. This is important for applications like algorithmic resolutions. We compare the Newton tree of a quasi-ordinary singularity and those of its curve transversal sections. We show that the Newton trees of the transversal sections do not give the tree of the quasi-ordinary singularity in general. It does if we know that the Newton tree of the quasi-ordinary singularity has only one arrow., 32 pages

In previous papers the authors gave formulae for generating series of classes (in the Grothendieck ring of complex quasi-projective varieties) of Hilbert schemes of zero-dimensional subschemes on smooth varieties and on orbifolds in terms of certain local data and the, so called, power structure over the corresponding ring. Here we give an analogue of these formulae for equivariant (with respect to an action of a finite group on a smooth variety) Hilbert schemes of zero-dimensional subschemes and compute some local generating series for an action of the cyclic group on a smooth surface.

Let C be an irreducible projective plane curve in the complex projective space P(2). The classification of such curves, up to the action of the automorphism group PGL(3, C) on P(2), is a very difficult open problem with many interesting connections. The main goal is to determine, for a given d, whether there exists a projective plane curve of degree d having a fixed number of singularities of given topological type. In this note we are mainly interested in the case when C is a rational curve. The aim of this article is to present some of the old conjectures and related problems, and to complete them with some results and new conjectures from the recent work of the authors.

In this work we show a singular K3 surface S of such that producing a counter-example to a conjecture of Veys.

It is a well-known result that one can associate to each embedded algrebroid surfaces (E.A.S.), such that mult(s)=2, and algebroid curve c(v) (not necesarilly reduced). On the other hand, is [5] we associate to each E.A.S. W a finite weighted tree Ar (W). In this work we prove that if S and S' are E.A.S. with m(S) = m(S')= 2, then Ar(S')= Ar(S) if and only if C(S) and C(s') are equisingular as non-reduced curves.