Abstract Paper aims In this study, effective strategies to combine and select forecasting methods are proposed. In the selection strategy, the best performing forecasting method from a pool of methods is selected based on its accuracy, whereas the combination strategies are based on the mean methods’ outputs and on the methods’ accuracy. Originality Despite the large amount of work in this area, the actual literature lacks of selection and combination strategies of forecasting methods for dealing with intermittent time series. Research method The included forecasting methods are state-of-the-art approaches applied to industrial and academics forecasting problems. Experiments were performed to evaluate the performance of the proposed strategies using a spare part data set of an industry of elevators and a data set from the M3-Competition. Main findings The results show that, in most cases, the accuracy of the demand forecasts can be improved when using the proposed selection and combination strategies. Implications for theory and practice The proposed methodology can be applied to forecasting problems, covering a variety of characteristics (e.g., intermittency, trend). The results reveal that combination strategies have potential application, perform better than state-of-the-art models, and have comparable accuracy in intermittent series. Thus, they can be employed to improve production planning activities.

RESUMO OBJETIVO Mesmo que o estresse seja conhecido há muito tempo como um fator provocativo para a doença de Graves, sua relação com a tireoidite de Hashimoto é mais controversa. Estudos sobre esse tema são escassos. O objetivo deste artigo é relatar um caso de Hashitoxicose induzida por estresse. RESULTADOS Aqui nós relatamos um caso de Hashitoxicose induzido por um evento psicológico estressante em uma mulher de 28 anos com tireoidite de Hashimoto. Ela permaneceu estável eutireoidiana por 12 anos. Ela veio a nossa observação pela primeira vez em abril de 2016, enquanto eutireoidiana. Voltou após 11 meses por causa de fadiga e palpitações, na ausência de dor no pescoço. Testes de função tireoidiana revelaram uma tireotoxicose moderada (TSH indetectável; T4F 36,94 pmol/L, valores normais 9,0-24,46; FT3 13,50 pmol/L, valores normais 3,07-6,14) com anticorpos negativos para o receptor de TSH. Nos últimos três meses ela experimentou um evento psicológico estressante. Os marcadores inflamatórios foram negativos e a contagem de leucócitos foi normal. A ultrassonografia da tireoide revelou um aumento modesto da vascularização. Hipotireoidismo subclínico transitório ocorreu após sete semanas e se recuperou espontaneamente. Na última visita, a paciente ainda estava em eutireoidismo. (TSH 1,01 mU/L; FT4 9,22 pmol/L; FT3 3,98 pmol/L). Também realizamos a sorotipagem e a genotipização do HLA. CONCLUSÃO Este caso demonstra que, similarmente à doença de Graves, também a Hashitoxicose pode ser desencadeada por eventos estressantes da vida.

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves’ disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves’ disease, Hashitoxicosis can also be triggered by stressful life events.

Introducción: La Enfermedad de Huntington (EH) es un trastorno neurodegenerativo; autosómico dominante, con expresividad variable y penetrancia completa. La prevalencia estimada es entre 1-4 cada 100.000 habitantes. Es causada por expansión de tripletes CAG en el exón 1 del gen IT-15 que conduce a la síntesis de una proteína con una región de poliglutaminas expandidas que forman agregados en el núcleo celular induciendo a la apoptosis. Los alelos normales presentan un número menor a 26 tripletes CAG, y aquellos con más de 40 conducirán siempre a la enfermedad. Alelos de entre 26 a 36 repetidos se consideran normales “mutables” y de 36 a 39 repetidos generan un riesgo aumentado de desarrollar la enfermedad. Objetivo: Poner a punto el diagnóstico molecular en una población uruguaya, mediante la determinación del tamaño exacto de la mutación en personas afectadas o con sospecha clínica de EH, mediante el uso de técnicas de biología molecular. Métodos: Pacientes de la Policlínica de Enfermedad de Parkinson y Movimientos Anormales del Hospital de Clínicas. La determinación del número de repetidos se realizó mediante técnicas de amplificación del ADN por PCR y posterior análisis en geles de poliacrilamida y secuenciación. Resultados: Realizamos el diagnóstico molecular de 16 pacientes, 15 con un diagnóstico clínico previo, y uno asintomático. Se descartó el diagnóstico de EH en otros dos individuos analizados. Conclusiones: Hemos logrado la puesta a punto del estudio molecular para la enfermedad de EH por primera vez en nuestro país. Esta prueba es de gran utilidad como diagnóstico confirmatorio, etiológico o diferencial de EH.

Introduction: Huntington disease (HD) is a neurodegenerative disorder with an autosomal dominant inheritance mode, complete penetrance and variable clinical expressivity. The estimated prevalence is 1 to 4 per 100.000 individuals. It is caused by a CAG triplet expansion in exon 1 of the IT-15 gene which codes for a protein with an enlarged polyglutamine region. This leads to the formation of protein aggregates in the cell nucleus and induces apoptosis. Normal alleles show less than 26 CAG repeats, and those over 40 always lead to the disease. Alleles with 26 to 36 repeats are considered normal “mutable” alleles and those between 36 to 39, are considered in a gray zone with increased risk of developing the disease. Aims: To develop a diagnosis of HD in a uruguayan population and determine the exact size of the mutation in clinically affected subjects using molecular biology techniques. Methods: Patients were derived from Neurology Clinic of the “Hospital de Clínicas”. The determination of the CAG repeat number was done using polymerase chain reaction (PCR) technique, subsequent analysis on polyacrilamide gels and sequencing. Results: We performed the molecular diagnosis in 18 patients with clinical suspicion of HD. Fifteen of them had a previous clinical diagnosis and one had no symptoms. Besides, in two additional individuals this test allowed us to discard HD. Conclusions: A molecular diagnostic for HD disease was developed for the first time in our country. This test is of great clinical utility as a confirmatory, etiological, or differential diagnosis.

The pharmacokinetic characteristics in serum and tissue of cefepime given intravenously (20 mg/kg body weight) were assessed in healthy rabbits and in rabbits with hyperthermia induced by lipopolysacharide of E. coli, with tissue fluid cages implanted subcutaneously. Ten adult rabbits were used in two trials (E1 and E2). Cefepime concentrations in serum (S) and tissue cage fluid (LT) were determined by biological methods. The kinetic analysis was performed by means of a noncompartmental model. Pharmacokinetic results (means ± standard error): half life of elimination [t1\2 (E1 S)=1.5±0.2 and (E2 S)=2.0±0.2 h] (p<0.05), area under the curve [ABC (E1 S)=181.6±17.5 and (E2 S)= 192.3±18.5 (µg/mL/h]; volume of distribution at steady-state [Vss (E1 S)=0.31±0.05 and (E2 S)=0.69±0.28 L/kg] (p<0.05); total serum clearance [CL (E1 S)=118.3±17.7 and (E2 S)=93.1±19.9 (mL/h)kg] (p<0.05); maximum concentration [Cmax (E1 LT)=23.5±3.4 and (E2 LT)=27.6±3.6 (µg/mL]; time to reach Cmax [t max (E1 LT) =2.3±0.4 and (E2 LT)=1.7±0.4 h)]; t1\2 (E1 LT)=2.4±0.3 and (E2 LT)=3.4±0.3 h (p<0.05); ABC (E1 LT)=122.0±12.7 and (E2 LT)=156.9±13.6 (µg/mL/h); penetration [P (E1 LT)=67.3±8.7 and (E2 LT)=88.5±8.7%]. In conclusion, the pharmacokinetic changes of cefepime observed in rabbits with hyperthermia induced by lipopolysacharide, could be clinically significant if not taken into account when designing the dosing regimens.

La farmacocinética sérica y tisular de cefepime administrado por vía endovenosa (20 mg/kg de peso) fue determinada en conejos sanos, con hipertermia producida por lipopolisacáridos de E. coli e implantados en tejido subcutáneo con cajas para recolección de líquido tisular. Diez conejos adultos fueron utilizados en dos experiencias (E1 y E2). Las concentraciones de cefepime en suero (S) y líquido tisular (LT) fueron determinadas por método biológico. Para el análisis cinético se utilizó un modelo no compartimental. Los resultados farmacocinéticos (medias ± error estándar) fueron: tiempo medio de eliminación [t1\2 (E1 S)=1,5±0,2 y (E2 S)=2,0±0,2 h] (p<0,05), área bajo la curva [ABC (E1 S)=181,6±17,5 y (E2 S)=192,3±18,5 (µg/mL/h]; Volumen de distribución en estado estacionario [Vss (E1S)=0,31±0,05 y (E2 S)=0,69±0,28 L/kg] (p<0,05); aclaramiento sérico [CL(E1 S)=118,3±17,7 y (E2 S) =93,1±19,9 (mL/h)kg] (p<0,05); Concentración máxima [Cmax (E1 LT)= 23,5±3,4 y (E2 LT)= 27,6±3,6 (µg/mL]; tiempo en el que se logra la Cmax [t max (E1 LT)=2,3±0,4 y (E2 LT)=1,7±0,4 h)]; t1/2 (E1 LT)= 2,4±0,3 y (E2 LT)=3,4±0,3 h (p<0,05); ABC (E1 LT)=122,0±12,7 y (E2 LT)=156,9±13,6 (µg/mL/h). y penetración [P (E1 LT)=67,3±8,7 y (E2 LT)=88,5±8,7%].

Extracts obtained from 57 marine-derived fungal strains were analyzed by HPLC-PDA, TLC and ¹H NMR. The analyses showed that the growth conditions affected the chemical profile of crude extracts. Furthermore, the majority of fungal strains which produced either bioactive of chemically distinctive crude extracts have been isolated from sediments or marine algae. The chemical investigation of the antimycobacterial and cytotoxic crude extract obtained from two strains of the fungus Beauveria felina have yielded cyclodepsipeptides related to destruxins. The present approach constitutes a valuable tool for the selection of fungal strains that produce chemically interesting or biologically active secondary metabolites.

Foram realizados dois experimentos com o objetivo de avaliar o efeito do condicionamento osmótico sobre a germinação de sementes de Triplaris americana, em condições normais e sob estresse. O primeiro experimento foi instalado em delineamento inteiramente casualizado com quatro repetições de 50 sementes e constituído dos tratamentos: T1: água (7 dias a 25ºC), T2: -1,5pa (NaCl), T3: -1,5Mpa (NaCl) + 25mg.L-1 -ácido giberélico (GA), T4: -0,25Mpa - polietilenoglicol (PEG), T5: - 0,25Mpa (PEG) + 25mg.L-1 (GA) , T6: controle. O segundo experimento foi conduzido em delineamento inteiramente casualizado com quatro repetições de 25 sementes, sob esquema fatorial 2x4, sendo duas condições de estresse e quatro condicionamentos. As condições de estresse foram envelhecimento acelerado (72 horas em BOD a 42ºC) e germinação à temperatura de 20ºC. Os tratamentos de condicionamentos utilizados foram: água, - 1,5Mpa (NaCl), -0,25Mpa (PEG), sem condicionamento (testemunha). Conclui-se que, em sementes não sujeitas à estresse, o condicionamento osmótico não aumenta o percentual de germinação e o peso seco de plântulas de pau-formiga, mas o condicionamento em água e em solução de PEG + GA proporciona maior velocidade de germinação. Em condições de estresse simulado, o condicionamento osmótico, principalmente em - 0,25Mpa (PEG), atua positivamente em aspectos relacionados à germinação de sementes de pau-formiga e o condicionamento em água apresenta potencial semelhante.

Two experiments were carried out to evaluate the effect of osmotic conditioning on the germination of Triplaris americana seeds, under nondormant and stress conditions. The first experiment was set up in a completaly randomized design with four replications of 50 seeds and the following treatments: T1: water (7 days at 25ºC), T2: - 1,5Mpa (NaCl) , T3: -1,5Mpa (NaCl) + 25mg.L-1 -giberellic acid (GA), T4: - 0,25Mpa - polyethylem glycol (PEG), T5: - 0,25Mpa (PEG) + 25mg.L-1 (GA) and T6: control. The second experiment was a completaly randomized design with four replications of 25 seeds, in a 2x4 factorial design, with two stress conditions and 4 conditionings. The stress conditions were accelerated aging (72 hours in germination chamber (BOD type), at 42ºC and germination at 20ºC. The following treatments were compared: water; -1,5Mpa (NaCl), - 0,25Mpa (PEG), without conditioning (control). It was confirmed that in seeds not subjected to stress, the osmotic conditioning did not increase the germination percentage and dry mass of Triplaris americana ("ant-wood"), but conditioning in water and in PEG + GA provided higher germination speed. In conditions of simulated stress, the osmotic conditioning, mainly in - 0,25 Mpa (PEG), acted positively in aspects related to Triplaris americana germination and conditioning in water presented similar potential.

A Sesbania virgataé uma espécie arbórea, pioneira e de ocorrência natural no Brasil. Pertence à família Leguminosae-Faboideae sendo recomendada para recuperação de áreas degradadas devido a sua rusticidade e capacidade de estabelecer simbiose com rizóbio. Mas, apesar de sua ampla distribuição, até o momento não havia uma descrição morfológica das estruturas de propagação e da planta na fase inicial de desenvolvimento. O objetivo deste trabalho foi descrever os caracteres morfológicos dos frutos, sementes e plântulas, bem como caracterizar o processo de germinação de Sesbania virgata. Para o estudo do fruto, os seguintes aspectos foram observados: tipo; cor; dimensões; textura e consistência do pericarpo; deiscência; e número de sementes por fruto. Os aspectos observados para as sementes foram: cor; dimensões; peso de 1000 sementes; textura e consistência dos tegumentos; forma; bordo, posição do hilo e de outras estruturas presentes e características do embrião. As plântulas foram caracterizadas em dois estádios. O estádio de plântula foi considerado quando os protófilos já estavam totalmente formados e de planta jovem, a partir do surgimento do 2° protófilo. Os elementos vegetativos descritos e ilustrados foram radícula, coleto, hipocótilo, cotilédones, epicótilo, protófilos e caule. O fruto de Sesbania virgata é um legume indeiscente medindo 5,8 cm e contendo de 2 a 6 sementes. A semente de Sesbania virgata é reniforme, endospérmica e desprovida do tegma, sendo que o hilo e o estrófíolo são facilmente distinguíveis. O eixo-embrionário encontra-se inserido aos cotilédones, sendo apical e invaginado papilonáceo. A germinação da semente é do tipo epígea. A plântula jovem apresenta protófilos compostos com 4 a 9 pares de folíolos pequenos opostos e glabros com peciolo e pulvino, e no ápice há uma pequena expansão laminar glabra. A radícula é sublenhosa, de cor branca ou marrom castanho.

Sesbania Virgata is a bush, pioneer and occurs naturally Brazil. It belongs to the Leguminosae-Faboideae family and is indicated for recovery-degraded areas due to its rusticity and capacity of establishing symbiosis with rhizobial. But, in spite of its wide distribution, to date there is no morphologic description of the propagation structures and the plantule. This study describes the morphologic characters of the fruits, seeds and plantules, and characterizes the germination process of Sesbania virgata. For the study of the fruit, the following aspects were observed: type; color; dimensions; texture and consistence of the pericarp; opening; and number of seeds per fruit. The aspects observed for the seeds were: color; dimensions; weigt of 1000 seeds; tegument texture and consistency; form; embroider (?), hilum and other structures position and embryo characteristics. The plantules were characterized at two stages. The plantule stage was considered when the foliage leaves were totally formed and at young plant stage starting from the appearance of the 2nd foliage leaf. The described and cultured vegetative elements were root (main and secondary), collar, hypocotyls, cotyledons, epicotyls, foliage leaf (1st and 2nd orders) and stem. The Sesbania Virgata fruit is an indehiscent legume measuring 5,8 cm with 2 to 6 seeds. The Sesbania Virgata seeds are kidney-shaped and endospermic and there is no internal tegument. The hilum and the strophiole are easily distinguishable. The apical axis-embryo is inserted in the cotyledons. The seed germination is the epigeal type.