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Introducción: El tiempo sigue siendo una variable determinante para los tratamientos de reper-fusión del ictus isquémico agudo. A pesar de las recomendaciones de las guías clínicas, soloalrededor de la tercera parte de los pacientes con ictus isquémico agudo son fibrinolizadosen = 60 min. El objetivo de este trabajo es describir nuestra experiencia implementando unprotocolo específico de atención del ictus isquémico agudo y evaluar su impacto en nuestrostiempos puerta-aguja. Métodos: A finales del 2015, se implantaron gradualmente unas medidas dise ~nadas para acortarlos tiempos de actuación y optimizar la atención del ictus isquémico agudo incluyendo unaguardia específica de Neurovascular. Se compararon los tiempos de actuación antes (2013-2015)y después (2017-2019) de la introducción de este protocolo. Resultados: Se incluyó a 182 pacientes antes y 249 después de la intervención. Cuando todas lasmedidas fueron introducidas, la mediana global de tiempo puerta-aguja fue de 45 min (previa74 min, 39% menos, p < 0, 001) con un 73, 5% de pacientes tratados en = 60 min (47% más quepreintervención, p < 0, 001). El tiempo global al tratamiento (inicio síntoma-aguja) se redujo en20 min de mediana (p < 0, 001). Conclusiones: Las medidas asociadas en nuestro protocolo han conseguido una disminución deltiempo puerta-aguja de forma significativa y sostenida, aunque todavía nos queda margen demejora, la dinámica establecida de control de resultados y mejora continua hará posible seguiravanzando en este sentido. Introduction: Time continues to be a fundamental variable in reperfusion treatments for acute ischaemic stroke. Despite the recommendations made in clinical guidelines, only around one-third of these patients receive fibrinolysis within 60 minutes. In this study, we describe our experience with the implementation of a specific protocol for patients with acute ischaemic stroke and evaluate its impact on door-to-needle times in our hospital. Methods: Measures were gradually implemented in late 2015 to shorten stroke management times and optimise the care provided to patients with acute ischaemic stroke; these measures included the creation of a specific on-call neurovascular care team. We compare stroke management times before (2013-2015) and after (2017-2019) the introduction of the protocol. Results: The study includes 182 patients attended before implementation of the protocol and 249 attended after. Once all measures were in effect, the overall median door-to-needle time was 45 minutes (vs 74 minutes before, a 39% reduction; P

PURPOSE: Few studies have examined the importance of improving the sexual health delivery system beyond HIV among trans women. We assessed survey data from the National HIV Behavioral Surveillance Transgender Woman (NHBS-Trans) Study in San Francisco to characterize the utilization of sexual health services among HIV-negative trans women and to explore opportunities to improve sexual health services for trans women. METHODS: Trans women were recruited through respondent-driven sampling from July 2019 to February 2020. The analytic sample was restricted to 116 HIV-negative trans women. We identified trends in data using chi-squared tests to assess significance between sexual risk behavior and the use of preventative sexual health services and built logistic regression models to assess the relationships between sexual risk behaviors and sexually transmitted infection (STI) testing. RESULTS: The majority of sample was trans women of color with most identifying as Latinx (42.2%). Over half were low income (56%), and majority had been homeless in past 12 months (62.9%). The prevalence of condomless receptive anal sex was 52.6% with about two-thirds (62.1%) recently having an STI test. Participants who engaged in recent condomless receptive anal sex had more than fivefold greater odds of having a recent STI test compared to their counterparts who did not (adjusted odds ratio [aOR] 5.60, 95% confidence interval [CI] 1.83–17.11; p=0.003). We also found age- and education-related disparities in STI testing. CONCLUSION: This study characterized the utilization of sexual health services among HIV-negative trans women and identified important disparities in STI testing. We discuss opportunities to strengthen sexual health care delivery systems.

Agri-food has become an economic sector under increasing pressure in order to support food demand and decrease environmental impacts. One valuable methodology to evaluate environmental impacts is life cycle assessment (LCA), which has been employed in different economic sectors, however, beekeeping has been scarcely explored. In this context, this article investigates the environmental profile of 31 Chilean beekeeping systems reporting 15 environmental impact categories with a cradle to gate approach. In this way, this study identifies key contributing activities, variability in the environmental impacts, differences among operation scales, and provided efficient management practices for policy-makers. To the best of our knowledge, this is the first study that conducts a wide environmental analysis of beekeeping systems through LCA. The results show that feeding is the most impacting activity in all categories, followed by hives transport. Otherwise, medication, consumption of disposable inputs and honey extraction contribute less than 5% in average across all categories. Regarding the operation scale, the results suggest that small-scale beekeepers have the lowest environmental performance. Otherwise, medium-scale beekeepers have better environmental performance than the large-scale ones, depending on the environmental impact category evaluated. Finally, managerial practices in order to achieve sustainable honey production are provided.

espanolPara identificar una patologia cada vez mas comun, conocida como mieloma multiple, es necesario hacer alusion de los factores especificos que la caracterizan. Para ello existen los clasicos criterios conocidos como CRAB (hipercalcemia, insufi- ciencia renal, anemia y lesiones liticas), siendo la insuficiencia renal una de sus complicaciones mas frecuentes. Reciente- mente se han descrito tres biomarcadores indiscutibles para el apoyo diagnostico del mieloma multiple, que son: mas del 10% de celulas plasmaticas clonales en medula osea o biopsia que corrobora la presencia de un plasmocitoma, relacion de cade- nas ligeras ≥ 100 mg/dl y mas de una lesion focal en resonancia magnetica. Se debe tomar siempre en cuenta el diagnostico diferencial con leucemia de celulas plasmaticas, plasmocitoma oseo solitario y plasmocitoma extramedular. Al ser una enfer- medad incurable, se ha investigado mucho en cuanto al manejo terapeutico, el cual tiene como objetivo principal la desapa- ricion de las celulas plasmaticas y la mejoria clinica del paciente. El primer farmaco que demostro algun beneficio fue el melfalan en el ano 1958 y posteriormente al adicionar un esteroide como segundo farmaco se logro mejorar las tasas de respuesta. Despues se fueron estudiando diferentes moleculas, con las que se han realizado multiples combinaciones, alcan- zando mejores tasas de supervivencia global y supervivencia libre de progresion. Anos mas tarde, con la llegada de los inhi- bidores de proteosoma como el bortezomib, asi como de los agentes inmunomoduladores como la talidomida y la lenalido- mida, se presenta un giro importante en la enfermedad, ya que se logran respuestas mas profundas, periodo de remisiones mas prolongadas y mejoria en la calidad de vida de los pacientes. Este consenso tiene la finalidad de integrar a un grupo de especialistas mexicanos y promover la actualizacion de esta patologia. EnglishTo identify this increasingly common pathology, known as Multiple Myeloma, it is necessary to refer to the specific factors that characterize it; to this end, the classic criteria known as CRAB (hypercalcemia, renal failure, anemia and lytic lesions) are available, in which renal failure is one of the most frequent complications. Recently, 3 indisputable biomarkers have been described for the diagnostic support for Multiple Myeloma, which are: more than 10% of clonal plasma cells in BM or, a biop- sy that corroborates the presence of a plasmacytoma, light chain ratio ≥100 mg/dL and more than one focal lesion on mag- netic resonance imaging (MRI). A differential diagnosis for plasma cell leukemia, solitary bone plasmacytoma, and extramed- ullary plasmacytoma should always be considered. Being this an incurable disease, a lot of research has been done regarding its therapeutic management, whose main objective is the disappearance of plasma cells and the patient clinical improvement. Melphalan was the first drug that showed a benefit in 1958 and afterwards, with the addition of a steroid as a second drug, it was possible to improve response rates. Subsequently, different molecules were studied, forming multiple combinations, and achieving better rates of Overall Survival and Progression-Free Survival. Years later, with the arrival of proteasome inhibitors such as bortezomib, and immunomodulators such as thalidomide and lenalidomide, an important turnaround in the disease has been seen, as deeper responses, more prolonged remissions, and improvement in the quality of life of patients have been achieved. This consensus has the purpose of integrating a group of Mexican specialists and promoting the updating of this pathology.

To identify this increasingly common pathology, known as multiple myeloma (MM), it is necessary to refer to the specific factors that characterize it; to this end, the classic criteria known as CRAB (hyperkalemia, renal failure, anemia, and lytic lesions) are available, in which renal failure is one of the most frequent complications. Recently, three indisputable biomarkers have been described for the diagnostic support for MM, which are: more than 10% of clonal plasma cells in bone marrow or, a biopsy that corroborates the presence of a plasmacytoma, light chain ratio ≥ 100 mg/dL and more than one focal lesion on magnetic resonance imaging. A differential diagnosis for plasma cell leukemia, solitary bone plasmacytoma, and extramedullary plasmacytoma should always be considered. Being this an incurable disease, a lot of research has been done regarding its therapeutic management, whose main objective is the disappearance of plasma cells and the patient clinical improvement. Melphalan was the first drug that showed a benefit in 1958 and afterward, with the addition of a steroid as a second drug, it was possible to improve response rates. Subsequently, different molecules were studied, forming multiple combinations, and achieving better rates of overall survival and progression-free survival. Years later, with the arrival of proteasome inhibitors such as bortezomib, and immunomodulators such as thalidomide and lenalidomide, an important turnaround in the disease has been seen, as deeper responses, more prolonged remissions, and improvement in the quality of life of patients have been achieved. This consensus has the purpose of integrating a group of Mexican specialists and promoting the updating of this pathology.

International and U.S. accounting standards mandate a one-step quantitative impairment test for goodwill and other indefinite-lived intangibles, but U.S. standards allow an optional qualitative assessment before the quantitative test. This option is intended to reduce the complexity and costs of the quantitative test. We demonstrate that U.S. firms using this option have comparatively higher valuations and face higher expected costs for conducting quantitative tests. Using a difference-in-differences research design, we show that firms using this option have a marginally higher incidence of impairments, suggesting that the qualitative assessment does not systematically allow companies to avoid write-downs. Moreover, we do not find clear evidence that using this option decreases the timeliness of impairments or increases monitoring costs for auditors, regulators, and investors. Our study provides evidence about the consequences of a revised impairment approach and speaks to the broader issue of allowing unconditional options and qualitative judgments in financial reporting. Data Availability: Data are available from public sources identified in the text. Hand-collected data are available upon request. JEL Classifications: M41; M42; M48.

Objective To describe baseline and procedural characteristics and clinical outcomes of isolated striatocapsular infarct (iSCI) after mechanical thrombectomy in patients with large-vessel occlusion of the anterior cerebral circulation and its clinical outcome. Methods We performed a longitudinal study including all patients treated with mechanical thrombectomy at our centre between 2015 and 2017; patients were divided into 2 groups (iSCI and non-iSCI) according to whether they presented iSCI in a control CT scan at 24 hours. Results Of the 83 patients identified, 22.9% developed an iSCI. There were no statically significant differences in baseline characteristics or in reperfusion times. Patients presenting iSCI showed better collateral circulation and better reperfusion rates in the bivariate analysis. No significant difference was observed for mortality at discharge or at 3 months, or for functional prognosis at 3 months. Conclusions Even if successful reperfusion is achieved, iSCI is a common sequela, independently of reperfusion time, especially in patients with good collateral circulation.

Introduction A better understanding of how menthol cigarette flavoring and ENDS impact smoking initiation, cessation, and transitions between tobacco products could help elucidate the potential impact of a U.S. menthol ban on combustible tobacco products. Methods A multistate transition model was applied to data on 23,232 adults from Waves 1–4 (2013–2017) of the Population Assessment of Tobacco and Health Study (analysis was conducted in 2020–2021). Transition rates among never, noncurrent, nonmenthol versus menthol cigarette, ENDS, and dual everyday/someday use were estimated, as were transition-specific hazard ratios for age, sex, race/ethnicity, education, and income. Results Non-Hispanic Blacks who smoked menthol discontinued smoking at a much lower rate than those who smoked nonmenthol (hazard ratio=0.43, 95% CI=0.29, 0.64), but there was no statistically significant difference in the discontinuation rates among non-Hispanic Whites (hazard ratio=0.97, 95% CI=0.80, 1.16) or Hispanics (hazard ratio=0.81, 95% CI=0.56, 1.16). Non-Hispanic Whites who smoked menthol were more likely to become dual users than those who smoked nonmenthol (hazard ratio=1.43, 95% CI=1.14, 1.80). Young adults initiated menthol smoking at a higher rate than older adults (age 18–24 years versus ≥55 years: hazard ratio=2.45, 95% CI=1.44, 4.15) but not nonmenthol smoking (hazard ratio=1.02, 95% CI=0.62, 1.69). There were differences by sex in the impact of menthol flavor on smoking initiation and discontinuation but little difference by education or income. Conclusions Sociodemographic differences in product transitions should be accounted for when estimating the potential impact of a menthol ban.

Treatment options for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) have increased dramatically over the past decade. However, even when novel approaches have proven to be effective as monotherapy, many patients still develop progressive disease, and different strategies are needed to increase clinical response and quality of life. Strategies combining targeted therapy (TT) and immunotherapy (IO) have emerged as a way to shorten the gap between responders and nonresponders to monotherapy and have reported promising results. In this review, we discuss the current role of cabozantinib in combination with IO agents in the treatment of metastatic RCC and UC and go over future directions in the field.Lay abstract Treatment options for both advanced kidney and bladder cancers have increased significantly over the last decade. However, even when these new approaches have proven to be effective, many patients still experience disease progression. Therefore, different strategies are needed to increase the response to treatment and quality of life. Strategies combining therapies directed to reduce the tumor's blood supply (targeted therapies) and therapies that increase the ability of the body to recognize and attack tumor cells (immunotherapy) have emerged as a way to increase the effectiveness obtained when using these drugs on their own. In this review, we discuss the current role of cabozantinib, a targeted therapy, in combination with immune-based agents in the treatment of advanced kidney and bladder cancers and go over future directions in the field.

The COVID‐19 pandemic had a severe impact on medical care. Our study aims to investigate the impact of COVID‐19 on advanced melanoma care in the Netherlands. We selected patients diagnosed with irresectable stage IIIc and IV melanoma during the first and second COVID‐19 wave and compared them with patients diagnosed within the same time frame in 2018 and 2019. Patients were divided into three geographical regions. We investigated baseline characteristics, time from diagnosis until start of systemic therapy and postponement of anti‐PD‐1 courses. During both waves, fewer patients were diagnosed compared to the control groups. During the first wave, time between diagnosis and start of treatment was significantly longer in the southern region compared to other regions (33 vs 9 and 15 days, P‐value, What's new? Little is known about the effects of COVID‐19 on advanced melanoma care. In this study, the authors examined several quality indicators of care. They observed a worsening in baseline characteristics, longer time between diagnosis and start of treatment and more postponed anti‐PD‐1 antibody courses with differences between the northern, middle and southern regions. Future studies are necessary to assess the long‐term consequences of our observed changes in advanced melanoma care.

Environmental arsenic exposure in adults and children has been associated with a reduction in the expression of club cell secretory protein (CC16) and an increase in the expression of matrix metalloproteinase-9 (MMP-9), both biomarkers of lung inflammation and negative respiratory outcomes. The objectives of this study were to determine if the levels of serum CC16 and MMP-9 and subsequent respiratory infections in children are associated with the ingestion of arsenic by drinking water. This cross-sectional study included 216 children from three Yaqui villages, Potam, Vicam, and Cocorit, with levels of arsenic in their ground water of 70.01 ± 21.85, 23.3 ± 9.99, and 11.8 ± 4.42 μg/L respectively. Total arsenic in water and urine samples was determined by inductively coupled plasma/optical emission spectrometry. Serum was analyzed for CC16 and MMP-9 using ELISA. The children had an average urinary arsenic of 79.39 μg/L and 46.8 % had levels above of the national concern value of 50 μg/L. Increased arsenic concentrations in drinking water and average daily arsenic intake by water were associated with decreased serum CC16 levels (β = − 0.12, 95% CI − 0.20, − 0.04 and β = − 0.10, 95% CI − 0.18, − 0.03), and increased serum MMP-9 levels (β = 0.35, 95% CI 0.22, 0.48 and β = 0.29, 95% CI 0.18, 0.40) at significant levels (P < 0.05). However, no association was found between levels of these serum biomarkers and urinary arsenic concentrations. In these children, reduced serum CC16 levels were significantly associated with increased risk of respiratory infections (OR = 0.34, 95% CI 0.13, 0.90). In conclusion, altered levels of serum CC16 and MMP-9 in the children may be due to the toxic effects of arsenic exposure through drinking water. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-13070-x.

RESUMEN El objetivo fue analizar la relación entre el uso de leña y la producción de dos tipos de ladrillos durante la etapa de cocción en olerías del distrito de Tobatí, Departamento de Cordillera, Paraguay. El estudio presentó dos etapas, la primera consistió en la aplicación de 392 encuestas al azar en olerías productoras de ladrillos prensados y comunes. La segunda se trató de la medición del consumo de leña, fueron medidas 3 olerías productoras de ladrillos prensados y 7 de ladrillos comunes, muestras determinadas utilizando los datos obtenidos en las encuestas. El promedio de producción anual de las olerías productoras de ladrillos comunes es de 460.693.491 unidades, con un consumo promedio anual de 128.640 metros estéreos de leña, en las olerías productoras de ladrillos prensados la producción promedio anual es de 175.803.581 unidades y el consumo promedio anual de leña es de 182.400 metros estéreos. El principal lugar de origen de la leña es la zona norte del país y la combinación de especies nativas y exóticas es la más empleada por las olerías. Con la medición se determinó que por cada metro cúbico de leña consumida se producen 7.604 unidades de ladrillos comunes y 2.142 unidades de ladrillos prensados. ABSTRACT The objective was to analyze the relationship between the use of firewood and the production of two types of brick during the cooking stage in brick factory of the district of Tobatí, Department of Cordillera, Paraguay. The study presented two stages, the first one consisted of the application of 392 random surveys in brick factories pressed and common. The second stage involved the measurement of firewood, were measured 3 pressed brick factory and 7 common, samples determined using the data obtained in the surveys. The average annual production of common brick production is 460,693,491 units, with an annual average consumption of 128,640 stereo meters of wood, in the brick-making production of pressed bricks the average annual production is 175,803,581 units and consumption. Average annual firewood is 182,400 stereo meters. The main origin of the firewood is the northern part of the country and the combination of native and exotic species is the most used by the bricks factory. With the measurement it was determined that for each cubic meter of wood consumed 7,604 units of common bricks and 2,142 units of pressed bricks are produced.

Vaccine hesitancy (VH) has emerged as a recognized threaten to contain the COVID-19 pandemic. Historically, low vaccine acceptance rates had been described among patients with rheumatic diseases (RMDs). The study objective was to determine COVID-19 VH among Mexican outpatients with RMDs and validate the COVID-19 VH questionnaire. This cross-sectional study was developed in three steps. Step 1 consisted of translation/cultural adaptation of the Oxford-COVID-19-VH questionnaire. Step 2 consisted of pilot testing and questionnaire feasibility, content, construct and criterion validity, reliability (internal consistency and temporal stability) and questionnaire sensitivity to change. Step 3 consisted of VH phenomenon quantification in patients from two metropolitan tertiary-care-level centers. Step 1 followed ISPOR-task-force recommendations. Patients who participated in step 2 (n = 50 for pilot testing/feasibility and n = 208 for questionnaire validation [91 in test–retest and 70 in questionnaire-sensitivity to change]) and step 3 (n = 600) were representative outpatients with RMDs. The seven-item COVID-19 VH questionnaire was found feasible, valid (experts’ agreement ≥80%; a 1-factor structure accounted for 60.73% of the total variance; rho = 0.156, p = .025 between COVID-19 VH questionnaire and score from the Spanish version of the Vaccine Hesitancy Scale; and lower questionnaire scores in patients who reported 5 years-previous influenza vaccination), reliable (Cronbach’s ɑ = 0.889, intra-class correlation coefficient = 0.933 and 95% confidence interval = 0.898–0.956) and sensitive to change (effect size = 1.17 and 0.86, respectively, in patients who decreased [n = 34] and increased [n = 31] questionnaire-score after intervention). VH phenomenon was 35.5%. VH phenomenon was present in a substantial number of Mexican patients with RMDs. The COVID-19 VH questionnaire showed good psychometric properties to assess COVID-19 VH in our population.

Study objective We retrospectively evaluated the implementation of low-threshold emergency department (ED) buprenorphine treatment at 52 hospitals participating in the CA Bridge Program using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. Methods The CA Bridge model included low-threshold buprenorphine, connection to outpatient care, and harm reduction. Implementation began in March 2019. Participating hospitals reported aggregated clinical data monthly after program initiation. Outcomes included identification of opioid use disorder, buprenorphine administration, and linkage to outpatient addiction treatment. Multivariable models assessed associations between hospital location (rural versus urban) and teaching status (clinical teaching hospital versus community hospital) and outcomes in adopting the CA Bridge Program. Results Reach: A diverse and geographically distributed group of 52 California hospitals were enrolled in 2 phases (March and August 2019); 12 (23%) were rural and 13 (25%) were teaching hospitals. Effectiveness: Over a 14-month implementation period, 12,009 opioid use disorder patient encounters were identified, including 7,179 (59.7%) where buprenorphine was administered and 4,818 (40.1%) where follow-up visits were attended. Adoption: In multivariable analysis, adoption did not differ significantly between rural and urban or teaching and nonteaching hospitals. Implementation: By program completion, all 52 (100%) hospitals treated opioid use disorder with buprenorphine; 45 (86.5%) administered buprenorphine after naloxone reversal; 41 (84.6%) offered buprenorphine for inpatients; 48 (92.3%) initiated buprenorphine in pregnant women; and 29 (55.8%) offered take-home naloxone. Maintenance: At 8-month follow-up, all 52 sites reported continued buprenorphine treatment. Conclusion Low-threshold ED buprenorphine treatment implemented with a harm reduction approach and active navigation to outpatient addiction treatment was successful in achieving buprenorphine treatment for opioid use disorder in diverse California communities.

Solid organ transplant recipients are at increased risk of acquiring devastating infections with unusual pathogens. Nocardia are aerobic actinomycetes that affect the lungs, brain, skin and soft tissue. Cladophialophora species are dematiaceous fungi that overwhelmingly cause infections in the brain. Both organisms carry a high mortality rate. We present the first reported renal transplant case with Cladophialophora bantiana involving the renal allograft with concurrent invasive nocardiosis involving the lungs and brain.

Agricultural science in Chile began in 1881 with the establishment of the Agronomic Station of the National Society of Agriculture (SNA). In this article we described the history and evolution of research and development (R+D) and human capital training in this field. The main research institution, in terms of territory coverage and human resources, is the Instituto de Investigaciones Agropecuarias (INIA), along with five regional research centers, specialized in different aspect of agricultural science, and 20 schools of agriculture and 11 doctoral programs associated to different universities. Public investment in agricultural R+D is provided by the Ministry of Agriculture, Ministry of Science and Technology, Ministry of Economy and Regional Governments, reaching around US$200 million in the last decade. The number of researchers in agricultural science is ~ 40 per million of inhabitants (~ 800 in total). An average of 140 projects per year are financed in agriculture R+D by different funding agencies. The scientific productivity was estimated in ~ 0.45 articles (Scopus) per researcher. It is concluded that, although significant progress has been made the last decades, there is still a reduced number of researchers and insufficient investment to face urgent challenges of the agricultural sector in Chile.

Pandemic restrictions have led to changes in therapy plans and disrupted rehabilitation services for people with multiple sclerosis. CogEx is an international, multicentre MS dual-intervention (cognitive rehabilitation, aerobic exercise) randomized, controlled rehabilitation trial confined to people with progressive disease. The primary outcome is cognition (processing speed).There are 11 treatment sites in six countries with participants required to make 27 site visits over 12 weeks. Collectively, the large, in-person demands of the trial, and the varying international policies for the containment of COVID-19, might disproportionately impact the administration of CogEx. During the first lockdown, all centres closed on average for 82.9 (SD = 24.3) days. One site was required to lockdown on two further occasions. One site remained closed for 16 months. Ten staff (19.2%) were required to quarantine and eight staff (15.4%) tested positive for COVID. 10 of 264 (3.8%) participants acquired COVID-19. All survived. The mean duration of enrollment delay has been [236.7 (SD = 214.5) days]. Restarting participants whose interventions were interrupted by the pandemic meant recalculating the intervention prescriptions for these individuals. While the impact of the pandemic on CogEx has been considerable, all study sites are again open. Participants and staff have shown considerable flexibility and resilience in keeping a complex, international endeavour running. The future in general remains uncertain in the midst of a pandemic, but there is cautious optimism the study will be completed with sufficient sample size to robustly evaluate our hypothesis and provide meaningful results to the MS community on the impact of these interventions on people with progressive MS. Trial registration: The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated.

Aim To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma. Material and methods The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways. Results Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2–2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8–9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response. Conclusion In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.

Slow periodic myoclonus is a well-recognized phenotype of fulminant subacute sclerosing panencephalitis (video 1).1 This distinctive phenotype has not been previously recognized in another rapidly progressive disorder, fulminant Wilson disease. We documented slow periodic myoclonus in a 34-year-old Peruvian man who developed paranoid schizophrenia and, 6 months later, levodopa-unresponsive parkinsonism and falls, progressing into akinetic mutism (video 2). Prior to death, the diagnosis of Wilson disease was supported by ocular and neuroimaging features (figure), low ceruloplasmin (5.3 U/L), high urinary copper, and diffuse hepatopathy on echography. Slow periodic flexor myoclonus reflects cortical excitability and bears a poor prognosis.2 The EEG correlates are generalized, high-amplitude, quasiperiodic complexes.

This article establishes opportunities of design as a tool in the generation of teaching resources. The study reflects weaknesses in the training process used by teachers, many are built intuitively without the technical support of this discipline. A qualitative research, raises the analysis of the performance of the teacher in the classroom, the methodologies and teaching resources used; The comparison of bibliographic criteria, allows to establish judgments about the correspondence between the educational environment and the conceptual design, and a practical theorical analysis based on the product design methodology and supported by the synthetic analytical method, is the basis to demonstrate the viability in the construction of the didactic material. The results obtainedreflect that the design process and its implementation generate a level of interaction between student and teacher and functions as a pedagogical tool to reinforce and sustain knowledge. Keywords: Design; teaching materials; processes; opportunity. References [1]Ministerio de Educación, Constitución del Ecuador, Quito, 2015. [2]Ministerio de Educación, Instructivo para planificaciones curriculares para el sistema nacional de educación, 2017. [3]Ministerio de educación, Guía Metodológica para la implementación del currículo para educación inicial, Quito, Ecuador, 2014, p. 34. [4]Z. Esteves, N. Garcés, V. Toala and E. Poveda, «La importancia del uso del material didáctico para la construcción de aprendizajes significativos,» Innova, 2018. [5]C. Villanueva and N. Rojas, Importancia del material didáctico en el aula de educación inicial en familia comunitaria, 2013. [6]Guerrero and Idrovo, Estudio del material didáctico de la metodología de rincones lúdicos en educación inicial, Cuenca: Universidad de Cuenca, 2010. [7]M. Manrique and M. Gallego, «El material didáctico para la construcción de aprendizajes significativos,» Revista Colombiana de Ciencias Sociales, 2013. 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In this paper, we applied a peer assessment scenario at the Technical University of Manabi (Ecuador). Students and professors evaluated some works through rubrics, assigned a numerical score, and provided textual feedback grounding why such a numerical score was determined, to detect inaccuracy between both assessments. The proposed model uses soft computing techniques to reduce the professor's workload in the correction process. Experiments were carried out with a data set in the Spanish language. We applied a supervised machine learning approach to obtain a sentiment score corresponding to specific textual feedback, and the fuzzy logic approach to detect inaccuracy between numerical and sentiment scores and obtain the assessment score. The results showed that the support vector machine model had a better performance with low computational costs when the feedback was represented as a 1-g and 2-g vector, whose relevance was weighted with term frequency-inverse document frequency; moreover, the grader's critical judgment validity was inferred from the similarities between numerical and sentiment scores. At the end, the outcomes assert the model is reliable and guarantees a fair peer assessment procedure.

En el Ecuador las empresas u organizaciones han implementado el uso de las herramientas que existen dentro del marketing digital para realizar mejorías en el estilo de la comunicación y de la interacción con sus clientes potenciales y sus posibles futuros clientes. El marketing digital en el mundo musical ha permitido que los propios artistas mejoren su capacidad de interacción con su público objetivo mediante el uso de las plataformas digitales. La presente investigación tiene como objetivo determinar las estrategias de marketing digital adecuadas, las cuales permitan a los artistas de la provincia de El Oro poder compartir su música a través de estas plataformas digitales. Se aplicó una investigación cualitativa con la elaboración y aplicación de una entrevista, utilizando una herramienta del marketing denominada Focus Group, en la que intervinieron varios artistas de la Provincia de El Oro. En los resultados se evidenció que la información y el uso del marketing digital es de entera importancia, para que los profesionales del medio musical puedan interactuar, llegar a ser competitivos dentro del mercado laboral, utilizando las herramientas que el marketing ofrece, para facilitar su trabajo e incrementar la difusión de su contenido artístico, para ser reconocidos dentro y fuera de la provincia y hasta poder llegar al reconocimiento Internacional.

Shape classification from binary images is a challenging task within the computer vision community. Commonly, contour and structural features are computed to describe the objects and code patterns robust against rotation, scaling, and shape deformation. However, current techniques get a high-dimensional feature space decreasing the system performance and the attribute interpretability. Here, we introduce an enhanced and interpretable feature representation approach to support shape classification from binary images. Our method, named EIFR, employs a bag of contour fragments-based feature estimation, intrinsically robust to occlusion and shape deformation. Then, a ReliefF-based feature selection is applied to filter non-discriminative attributes. In turn, a kernel-alignment-based projection is used to measure the feature relevance enhancing the data representation through the matching between a similarity matrix computed from filtered attributes and a kernel matrix built from the shape labels. Attained results on benchmark datasets prove that EIFR improves the curvature-based features’ interpretability and favors the classification performance.

Introduction Experts recommend integrating smoking-cessation treatments within U.S. mental health settings, but the population health benefits of doing so have not been estimated. This study simulates the impact of widespread cessation treatment for patients with depression under best-case treatment and maximum potential cessation scenarios. Methods Cessation interventions were simulated for U.S. adult smokers seeing a health professional for depression from 2020 to 2100. Interventions included (1) Any Treatment (behavioral counseling, pharmacological, combination) and (2) Pharmacological Treatment (including counseling), combined with increased mental health service utilization each. These were compared with a maximum potential cessation scenario where all patients with major depression quit smoking. Analyses were conducted in 2016–2020. Results Widespread uptake of Any Treatment among patients with depression would avert 32,000 deaths and result in 138,000 life-years gained by 2100; Any Treatment combined with 100% mental health service utilization would result in 53,000 and 231,000, respectively. Pharmacological Treatment would avert 125,000 deaths, with 540,000 life-years gained. Pharmacological Treatment combined with 100% mental health service utilization would result in 203,000 deaths averted and 887,000 life-years gained. Health gains under best-case treatment scenarios represent modest fractions of those projected under maximum potential cessation scenarios at current mental health service utilization levels (835,000 deaths averted, 3.73 million life-years gained) and at 100% utilization (1.11 million deaths averted, 5.07 million life years gained). Conclusions Providing smoking-cessation treatment to patients with depression and increasing mental health service utilization would reduce the toll of tobacco on this population. These gains would be considerably larger if cessation treatments were more effective.

Avascular necrosis of the femoral (AVN) head is a disabling disease that affects function, mobility, and quality of life in the young adult. Its pathology involves blood circulation disruption of the femoral head and subchondral infarction. This leads to cartilage thinning, femoral head depression, and cartilage breakage, which results in hip osteoarthritis. In the past decade the prevalence of intraarticular pathology has been almost 95%, this revealed with hip arthroscopy (HA). HA and core decompression (CD) of the femoral head can be used effectively and concomitantly to treat AVN with excellent results, HA allows for excellent visualization of the hip joint cartilage, allowing treatment of femoroacetabular impingement syndrome (FAIS) and intra-articular pathology. Our technique demonstrates that retrograde core decompression with allograft and mixed bone matrix is an excellent choice of treatment in the early stages of AVN/ONFH. The femoral head–specific aiming guide is very reliable, is simple to use arthroscopically if placed in the posterolateral portal of the hip, and offers exact pin placement at the necrotic site, as well as less operative time and less radiation to the patient and surgical team., Technique Video Video 1 The patient is positioned in the modified supine position. The hip is distracted with a specialized hip distractor. The upper body of the patient is prepared in a Tutankhamun fashion, and both arms are placed over the chest in a figure-8 or X position. Bony prominences are protected at the level of the elbows and wrists. Hands are left free for intravenous line for medication passage, which is double-checked by the anesthesiologist. The nonoperative hip is positioned in flexion, abduction, and external rotation to permit the passage of the image intensifier and take perfect fluoroscopic images. The hip is prepped and draped in a standard fashion, anatomic landmarks are marked on the patient’s operative hip, 3 to 5 portals are established to assess the peripheral and central compartments. An anterolateral portal (AL) is used for vision, immediately to the trochanteric tip. A peritrochanteric space portal is used as a working portal, and a midanterior portal is located 1.5 cm above and between the anterolateral and peritrochanteric space portals and a posterior portal (PP) to introduce the femoral head aiming guide (Parcus Medical, Sarasota, FL). The anterior hip bursa is resected with a shaver and cauterized if there is a bleeding with a radiofrequency wand (RF). An anterior longitudinal capsulotomy is performed posteriorly to access the head-neck junction and perform a femoro-osteochondroplasty of the cam morphology without hip traction. Distraction is made under arthroscopic vision to enter the CC; exchange to a 70° scope with switching sticks in a Seldinger technique is performed when entering the CC to observe the femoral head cartilage, labrum, chondrolabral junction, ligamentum teres, and acetabular fossa. If a labral tear exists, it is tackled in a standard fashion with 1.8- or 2.8-mm anchors (Parcus Medical, Sarasota, FL) (Fig 3). With fluoroscopic assistance and guidance, we confirm the location of the necrotic lesion, followed by an exhaustive examination and palpation with a ballotment test that is performed with an arthroscopic hook palpator or a blunt obturator. Here the specific femoral head aiming guide (Parcus Medical) is placed in the site of necrosis on the femoral head. It is very important to introduce the aiming guide through the posterior portal along the posterior line of the femoral cortex with maximal internal rotation of the hip to place the guide pin in the center of the femur and toward the necrotic lesion and to have perfect placement of the aiming guide observed in the fluoroscope image. After proper placement of the femoral head, a guide pin is passed toward the femoral head at the site of the necrosis with fluoroscopic guidance (Fig 4, Fig 5, Fig 6). Posteriorly a 5 mm reamer is passed through the guide pin; it is important to perform a longitudinal incision at the trochanteric crest, and blunt dissection is carried down to the tensor fascia lata to expose the lateral cortex of the femur where the reamer will break this cortex aimed toward the femoral head. We continue with retrograde femoral head decompression with low profile headed reamers from 5 mm to 10 or 12 mm depending on the size of the lesion. Pay careful attention when reaming close to the subchondral bone of the femoral head. Posteriorly a specialized loop curette is introduced to the core tract, and removal of remaining sclerotic bone is performed, where we exchange for a 30° scope to observe the core and make a thorough lavage with the arthroscopic sheath. Next, cancellous bone allograft in chips is mixed with bone-demineralized matrix and blood obtained from the decompressed tract; this mixture is impacted and pushed in a retrograde fashion with specialized XL blunt bone tamps and impactors until the core tract is filled.