Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.

IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409.

Design of highly focused fields that remain unpolarized on axis

Research on the properties of highly focused fields mainly involved fully polarized light, whereas partially polarized waves received less attention. The aim of this Letter is to provide an appropriate framework, for designing some features of the focused field, when dealing with incoming partially polarized beams. In particular, in this Letter, we describe how to get an unpolarized field on the axis of a high numerical aperture objective lens. Some numerical results that corroborate theoretical predictions are provided.

Nematode community, trophic structure and population fluctuation in soybean fields

Temporal (monthly in three fields for 12 months) and spatial (once in 23 fields during March-April) samplings were conducted in the major soybean (Glycine max)-growing region of the Brazilian Federal District. Fifty-three nematode genera were found in both samplings, but 13 were detected only by the temporal sampling, and one only by the spatial sampling. Fifty-three percent were plant-parasites, 35% were bacterivores, and about 12% were fungivores, predators and omnivores constituted the community that was dominated by the genera Helicotylenchus (40% of total abundance), Acrobeles (15%), Cephalobus (7.6%), Meloidogyne(5.6%) and Pratylenchus (4.9%). Heterodera glycines was not found in this study. There were no differences in ten ecological measurements [Ds, H', Es, T, FF/BF, (FF+BF)/PP, MI, PPI, mMI, and Dorylaimida (%)] between the two sampling types, but differences in indexes d and J'. Plant parasite populations dropped at the end of the crop cycle, remained at low levels during the dry season and the seedling period, then increased again in the crop-growing season. Fungivores maintained their low populations throughout the year, increasing only in June and July, the post-harvest period, when soil fungi decomposed root tissue. The population of bacterivores slightly declined during the dry season and the initial rainy season, but peaked in the middle of the rainy season, apparently associated with soil humidity. In the five most abundant nematodes, those of Acrobeles and Pratylenchus were more populous in wet soils, Cephalobus and Meloidogyne adapted well in dry soils, but Helicotylenchus survived abundantly in a wide range of soil moisture.

Virulence pattern of Pyricularia grisea isolates from farmers' fields on newly released upland rice cultivars

The virulence pattern of the isolates of Pyricularia grisea from commercial fields of the upland rice (Oryza sativa) cultivars 'Primavera' and 'BRS Bonança' was analyzed. A hundred and seventy monoconidial isolates of the pathogen virulent to 'Primavera' and 139 to 'BRS Bonança' collected from eight fields, during two years (2001-2003) were tested, under greenhouse conditions, on six newly released rice cultivars. Differences in virulence pattern were observed in pathogenic populations of 'Primavera' and 'BRS Bonança'. Isolates with virulence to improved cultivars were common in samples from farmers' fields in the absence of aloinfection. The virulence frequency of P. grisea isolates collected from 'Primavera'' to cultivars 'BRS Vencedora', 'BRS Colosso', 'BRS Liderança', 'BRS Soberana', 'BRS Curinga' and 'BRS Talento', was high in descending order. On the other hand, in the fungus population of 'BRS BRS Bonança' virulence frequency was high in 'BRS Talento', followed by 'BRS Curinga', 'BRS Vencedora', 'BRS Liderança', 'BRS Colosso' and 'BRS Soberana'. While virulence to 'BRS Talento' was rare among isolates from 'Primavera', it was most frequent in isolates of 'BRS Bonança'. The six improved rice cultivars permitted to differentiating agriculturally important virulences in the pathogen population which can be utilized in selecting breeding lines for specific resistance, in rice blast improvement program.

Natural regeneration in abandoned fields following intensive agricultural land use in an Atlantic Forest Island, Brazil

The time required to regrowth a forest in degraded areas depends on how the forest is removed and on the type of land use following removal. Natural regeneration was studied in abandoned old fields after intensive agricultural land use in areas originally covered by Brazilian Atlantic Forests of the Anchieta Island, Brazil in order to understand how plant communities reassemble following human disturbances as well as to determine suitable strategies of forest restoration. The fields were classified into three vegetation types according to the dominant plant species in: 1) Miconia albicans (Sw.) Triana (Melastomataceae) fields, 2) Dicranopteris flexuosa (Schrader) Underw. (Gleicheniaceae) thickets, and 3) Gleichenella pectinata (Willd.) Ching. (Gleicheniaceae) thickets. Both composition and structure of natural regeneration were compared among the three dominant vegetation types by establishing randomly three plots of 1 x 3 m in five sites of the island. A gradient in composition and abundance of species in natural regeneration could be observed along vegetation types from Dicranopteris fern thickets to Miconia fields. The gradient did not accurately follow the pattern of spatial distribution of the three dominant vegetation types in the island regarding their proximity of the remnant forests. A complex association of biotic and abiotic factors seems to be affecting the seedling recruitment and establishment in the study plots. The lowest plant regeneration found in Dicranopteris and Gleichenella thickets suggests that the ferns inhibit the recruitment of woody and herbaceous species. Otherwise, we could not distinguish different patterns of tree regeneration among the three vegetation types. Our results showed that forest recovery following severe anthropogenic disturbances is not direct, predictable or even achievable on its own. Appropriated actions and methods such as fern removal, planting ground covers, and enrichment planting with tree species were suggested in order to restore the natural forest regeneration process in the abandoned old fields.

Fungicide application using a trailing boom in soybean fields

The objective of this study was to determine the effects in the yield of soybean crop utilizing a trailing boom sprayer for chemical control of late season diseases. The experimental design was randomized blocks with 04 treatments, which consisted of applying fungicides with a traditional sprayer, trailing boom, the traditional sprayer plus the trailing boom simultaneously and control (without fungicide aerial application) in 05 repetitions per treatment. The variables evaluated were: final plant population, pods per plant, grains per pod, weight of one thousand grains and yield. It was concluded that the control of foliar diseases with fungicides presented weight of one thousand grains and yield significantly higher than the average of plots without fungicide application. The trailing boom did not significantly affect the yield compared to the technology currently used.

The importance of Leptospira interrogans serovars Icterohaemorrhagiae and Canicola in coastal zone and in southern fields of Rio Grande do Sul, Brazil

This study aimed to describe the occurrence of Leptospira interrogans serovars Icterohaemorrhagiae and Canicola, in coastal zone and in southern grasslands of Rio Grande do Sul, Brazil. In each one of the four analyzed farms blood samples were collected from free-living wild animals, domestic animals and humans to perform serological testing for leptospirosis. The presence of antibodies was verified by microscopic agglutination test (MAT). The criterion adopted to consider a serum as agglutination reactant was at least 50% of leptospira for a microscopic field of 100x. From 17 blood samples collected at Chuí, five (29.41%) were positive, three (60.00%) for serovar Icterohaemorrhagiae and two (40.00%) for Canicola. From 21 samples collected in the County of Santana da Boa Vista, six (28.57%) were positive, four (66.67%) for serovar Canicola and two (33.33%) for serovar Icterohaemorrhagiae. From 32 samples collected at Alegrete, 10 (31.25%) were positive, seven (70.00%) for serovar Icterohaemorrhagiae and three (30.00%) foro serovar Canicola. From 17 blood samples collected in Cruz Alta, three (17.64%) were positive, two (66.67%) for serovar Icterohaemorrhagiae and one (33.33%) for Canicola. It is necessary to improve sanitary practices on farms in the state of Rio Grande do Sul, in order to achieve success in leptospirosis control programs.

From the seeds of rediscovered texts come new fields of inquiry

Kirjallisuusarvostelu

Unexpected effects of pigeon-peas (Cajanus cajan) in the restoration of rupestrian fields

Several degraded areas can be found along the Highway MG-010 that crosses the Espinhaço Mountain Biosphere Reserve in the Brazilian state of Minas Gerais. Restoration by planting the legume Cajanus cajan was implemented in some of these areas. The present study compares plant species richness, diversity, abundance, equitability, similarity, and soil composition between restored and non-restored areas, in an attempt to evaluate the effectiveness of the use of C. cajan in the restoration process in the mountain environment. Each treatment (restored and non-restored) had four sampling areas, each with three 300 m² plots. We counted and identified every individual plant found within these plots. We also collected soil from the superficial layer (0-10 cm) of each sampling area in both treatments. The areas where C. cajan was planted revealed lower species richness, diversity, and plant abundance. The soil of these areas also contained higher levels of Phosphorus and Magnesium. Plant equitability and similarity between plots and other soil components (pH, Nitrogen, Aluminum, Calcium, Potassium, H+Al, sum of bases - SB, cation exchange capacity - CTC, base saturation - V%, aluminum saturation - M%) did not differ between the two treatments. Contrary to the expectations, soil enhancement in the quartzitic soil poor in nutrients in the rupestrian fields can facilitate the invasion by exotic plants, which are not adapted to the lack of nutrients. As it appears, the use of C. cajan in restoration projects represents a mistake and future restoration plans should avoid the use of exotic species, given that they may cause negative effects on the native plant community, as demonstrated here in the rupestrian fields.

Limits of Meritocracy. How Fields of Study and Gender Segregation Affect Social Stratification in Finland

This dissertation critically reviews the idea of meritocracy from both a theoretical and an empirical perspective. Based on a discussion of classical texts of social philosophy and sociology, it is argued that meritocracy as a concept for social stratification is best compatible with the sociological tradition of status attainment research: both frame social inequality in primarily individualistic terms, centring on the role of ascribed (e.g., gender, social background) and achieved (e.g., educational qualifications) characteristics for determining individuals’ socioeconomic rewards. This theoretical argument introduces the research problem at the core of this dissertation: to what extent can the individualistic conception of social stratification be maintained empirically? Fields of study and their interaction with educational attainment levels play a prominent role in the analysis of this question. Drawing on sociological versions of segmented labour market theory, it is assumed that fields of study may channel individuals into heterogeneous political-economic contexts on the labour market, which potentially modify the socioeconomic benefit individuals derive from their qualification levels. The focus on fields of study may also highlight economic differentials between men and women that derive from the persisting segregation of men’s and women’s occupational and educational specializations rather than direct gender discrimination on the labour market. The quantitative analyses in this dissertation consist of three research articles, which are based primarily on Finnish data, but occasionally extend the view to other European countries. The data sources include register-based macro- and microdata as well as survey data. Article I examines the extent and the patterns of gender segregation within the Finnish educational system between 1981 and 2005. The results show that differences between men’s and women’s field specializations have for the most part remained stable during this period, with particularly high levels of gender segregation observed at lower educational levels. The focus in Article II rests on the effects of gender-segregated fields of study on higher education graduates’ occupational status. It is shown that fields of study matter for accessing professional jobs and avoiding low-skilled positions in Finland: at the early career stage, particularly polytechnic graduates from female-dominated fields are less likely to work in professional positions. Finnish university graduates from male-dominated fields were more likely than their peers with different specializations to work as professionals, yet they also faced a greater risk of being sorted into lowskilled jobs if they failed to make use of this advantage. Article III proceeded to analyse the joint impact of educational qualification levels and fields of study on young adults’ median earnings in Finland between 1985 and 2005. The results show that qualification levels do not confer a consistent benefit in the process of earnings stratification. Advanced qualifications raise median earnings most clearly among individuals specializing in the same field of study. When comparing individuals with different field specializations, on the other hand, higher-level qualifications do not necessarily lead to higher median earnings. Overall, the findings of this dissertation reveal a heterogeneous effect of education for achieving social positions, which challenges individual-centred, meritocratic accounts of social stratification and underlines the problematic lack of structural and institutional dimensions in the dominant account of social status attainment.

JNK regulates dendrite and spine architecture in the central nervous system influencing spatial learning and motor tasks

JNK1 is a MAP-kinase that has proven a significant player in the central nervous system. It regulates brain development and the maintenance of dendrites and axons. Several novel phosphorylation targets of JNK1 were identified in a screen performed in the Coffey lab. These proteins were mainly involved in the regulation of neuronal cytoskeleton, influencing the dynamics and stability of microtubules and actin. These structural proteins form the dynamic backbone for the elaborate architecture of the dendritic tree of a neuron. The initiation and branching of the dendrites requires a dynamic interplay between the cytoskeletal building blocks. Both microtubules and actin are decorated by associated proteins which regulate their dynamics. The dendrite-specific, high molecular weight microtubule associated protein 2 (MAP2) is an abundant protein in the brain, the binding of which stabilizes microtubules and influences their bundling. Its expression in non-neuronal cells induces the formation of neurite-like processes from the cell body, and its function is highly regulated by phosphorylation. JNK1 was shown to phosphorylate the proline-rich domain of MAP2 in vivo in a previous study performed in the group. Here we verify three threonine residues (T1619, T1622 and T1625) as JNK1 targets, the phosphorylation of which increases the binding of MAP2 to microtubules. This binding stabilizes the microtubules and increases process formation in non-neuronal cells. Phosphorylation-site mutants were engineered in the lab. The non-phosphorylatable mutant of MAP2 (MAP2- T1619A, T1622A, T1625A) in these residues fails to bind microtubules, while the pseudo-phosphorylated form, MAP2- T1619D, T1622D, Thr1625D, efficiently binds and induces process formation even without the presence of active JNK1. Ectopic expression of the MAP2- T1619D, T1622D, Thr1625D in vivo in mouse brain led to a striking increase in the branching of cortical layer 2/3 (L2/3) pyramidal neurons, compared to MAP2-WT. The dendritic complexity defines the receptive field of a neuron and dictates the output to the postsynaptic cells. Previous studies in the group indicated altered dendrite architecture of the pyramidal neurons in the Jnk1-/- mouse motor cortex. Here, we used Lucifer Yellow loading and Sholl analysis of neurons in order to study the dendritic branching in more detail. We report a striking, opposing effect in the absence of Jnk1 in the cortical layers 2/3 and 5 of the primary motor cortex. The basal dendrites of pyramidal neurons close to the pial surface at L2/3 show a reduced complexity. In contrast, the L5 neurons, which receive massive input from the L2/3 neurons, show greatly increased branching. Another novel substrate identified for JNK1 was MARCKSL1, a protein that regulates actin dynamics. It is highly expressed in neurons, but also in various cancer tissues. Three phosphorylation target residues for JNK1 were identified, and it was demonstrated that their phosphorylation reduces actin turnover and retards migration of these cells. Actin is the main cytoskeletal component in dendritic spines, the site of most excitatory synapses in pyramidal neurons. The density and gross morphology of the Lucifer Yellow filled dendrites were characterized and we show reduced density and altered morphology of spines in the motor cortex and in the hippocampal area CA3. The dynamic dendritic spines are widely considered to function as the cellular correlate during learning. We used a Morris water maze to test spatial memory. Here, the wild-type mice outperformed the knock-out mice during the acquisition phase of the experiment indicating impaired special memory. The L5 pyramidal neurons of the motor cortex project to the spinal cord and regulate the movement of distinct muscle groups. Thus the altered dendrite morphology in the motor cortex was expected to have an effect on the input-output balance in the signaling from the cortex to the lower motor circuits. A battery of behavioral tests were conducted for the wild-type and Jnk1-/- mice, and the knock-outs performed poorly compared to wild-type mice in tests assessing balance and fine motor movements. This study expands our knowledge of JNK1 as an important regulator of the dendritic fields of neurons and their manifestations in behavior.

Map of a part of eastern Asia to show the commercial position of the productive coal fields of Yesso, Japan

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

A tour from the City of New-York, to Detroit, in the Michigan Territory, made between the 2d of May and the 22d of September, 1818 : the tour extends from New-York, by Albany, Schenectady, and Utica to Sacket's Harbor, and thence throught Lake Ontario, to St. Lawrence river, and down that stream to Hamilton village. Thence along both banks of the St. Lawrence, from Hamilton to the Thousand Islands; thence to Sacket's Harbor by water; from that place by the route of great Sodus, Geneva, Cananaigua and Batavia, to Buffalo; and from thence to Black Rock, Fort Erie, the Falls of Niagara, Queenston, Lewiston, and the memorable fields of Bridgewater and Chippewa after viewing the interesting place of Niagara, the author traversed the south shore of Lake Erie to the City of Detroit, and visited in the latter range, Dunkirk, Erie, Cleveland, Sandusky, and other places of less note. The tour is accompanied with a map upon which the route will be designated; a particular map of the Falls andRiver of Niagara, and the environs of the City of Detroit /

Errata slip inserted.