GAMEC – a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours

There is no consensus as to the management of untreated poor prognosis or relapsed/refractory germ cell tumours. We have studied an intensive cisplatin-based regimen that incorporates high-dose methotrexate (HD MTX) and actinomycin-D and etoposide every 14 days (GAMEC). Sixty-two patients were enrolled in a phase 2 study including 27 who were untreated (IGCCCG, poor prognosis) and 35 with progression despite conventional platinum based chemotherapy. The pharmacokinetics of the drugs were correlated with standard outcome measures. Twenty of the untreated patients were progression free following GAMEC and appropriate surgery, as were 18 individuals in the pretreated group. None of the established prognostic factors for therapy for pretreated patients could identify a poor-prognosis group. Five out of nine late relapses to prior chemotherapy were progression free following GAMEC and appropriate surgery. All patients had at least one episode of febrile neutropenia and there were five (8%) treatment-related deaths. PK values were not predictive of efficacy or toxicity, although the dose intensity in the pretreated group of patients, especially of HD MTX, was significantly correlated with progression-free survival (PFS). GAMEC is a novel intensive regimen for this group of patients producing encouraging responses, although with significant toxicity. For those in whom it fails, further therapy is still possible with durable responses being seen

Contrastive prosody and the subsequent mention of alternatives during discourse processing

Linguistic research has long viewed prosody as an important indicator of information structure in intonationally rich languages like English. Correspondingly, numerous psycholinguistic studies have shown significant effects of prosody, particularly with respect to the immediate processing of a prosodically prominent phrase. Although co-reference resolution is known to be influenced by information structure, it has been less clear whether prosodic prominence can affect decisions about next mention in a discourse, and if so, how. We present results from an open-ended story continuation task, conducted as part of a series of experiments that examine how prosody influences the anticipation and resolution of co-reference. Overall results from the project suggest that prosodic prominence can increase or decrease reference to a saliently pitch-accented phrase, depending on additional circumstances of the referential decision. We argue that an adequate account of prosody’s role in co-reference requires consideration of how the processing system interfaces with multiple levels of linguistic representation

Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer

Background: Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin. Methods: In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR. Results: Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate-severe) SOS (P=0.026). Conclusion: The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment

Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL)

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC

RECIST revised: implications for the radiologist. A review article on the modified RECIST guideline

The purpose of this review article is to familiarize radiologists with the recently revised Response Evaluation Criteria in Solid Tumours (RECIST), used in many anticancer drug trials to assess response and progression rate. The most important modifications are: a reduction in the maximum number of target lesions from ten to five, with a maximum of two per organ, with a longest diameter of at least 10 mm; in lymph nodes (LNs) the short axis rather than the long axis should be measured, with normal LN measuring <10 mm, non-target LN ≥10 mm but <15 mm and target LN ≥15 mm; osteolytic lesions with a soft tissue component and cystic tumours may serve as target lesions; an additional requirement for progressive disease (PD) of target lesions is not only a ≥20% increase in the sum of the longest diameter (SLD) from the nadir but also a ≥5 mm absolute increase in the SLD (the other response categories of target lesion are unchanged); PD of non-target lesions can only be applied if the increase in non-target lesions is representative of change in overall tumour burden; detailed imaging guidelines. Alternative response criteria in patients with hepatocellular carcinoma and gastrointestinal stromal tumours are discussed

On the origin of the invasive olives (Olea europaea L., Oleaceae).

The olive tree (Olea europaea) has successfully invaded several regions in Australia and Pacific islands. Two olive subspecies (subspp. europaea and cuspidata) were first introduced in these areas during the nineteenth century. In the present study, we determine the origin of invasive olives and investigate the importance of historical effects on the genetic diversity of populations. Four invasive populations from Australia and Hawaii were characterized using eight nuclear DNA microsatellites, plastid DNA markers as well as ITS-1 sequences. Based on these data, their genetic similarity with native populations was investigated, and it was determined that East Australian and Hawaiian populations (subsp. cuspidata) have originated from southern Africa while South Australian populations (subsp. europaea) have mostly derived from western or central Mediterranean cultivars. Invasive populations of subsp. cuspidata showed significant loss of genetic diversity in comparison to a putative source population, and a recent bottleneck was evidenced in Hawaii. Conversely, invasive populations of subsp. europaea did not display significant loss of genetic diversity in comparison to a native Mediterranean population. Different histories of invasion were inferred for these two taxa with multiple cultivars introduced restoring gene diversity for europaea and a single successful founder event and sequential introductions to East Australia and then Hawaii for cuspidata. Furthermore, one hybrid (cuspidata x europaea) was identified in East Australia. The importance of hybridizations in the future evolution of the olive invasiveness remains to be investigated

Conservation genetics of the annual hemiparasitic plant Melampyrum sylvaticum (Orobanchaceae) in the UK and Scandinavia

Melampyrum sylvaticum is an endangered annual hemiparasitic plant that is found in only 19 small and isolated populations in the United Kingdom (UK). To evaluate the genetic consequences of this patchy distribution we compared levels of diversity, inbreeding and differentiation from ten populations from the UK with eight relatively large populations from Sweden and Norway where the species is more continuously distributed. We demonstrate that in both the UK and Scandinavia, the species is highly inbreeding (global F IS = 0.899). Levels of population differentiation were high (F’ST = 0.892) and significantly higher amongst UK populations (F’ST = 0.949) than Scandinavian populations (F’ST = 0.762; P < 0.01). The isolated populations in the UK have, on average, lower genetic diversity (allelic richness, proportion of loci that are polymorphic, gene diversity) than Scandinavian populations, and this diversity difference is associated with the smaller census size and population area of UK populations. From a conservation perspective, the naturally inbreeding nature of the species may buffer the species against immediate effects of inbreeding depression, but the markedly lower levels of genetic diversity in UK populations may represent a genetic constraint to evolutionary change. In addition, the high levels of population differentiation suggest that gene flow among populations will not be effective at replenishing lost variation. We thus recommend supporting in situ conservation management with ex situ populations and human-mediated seed dispersal among selected populations in the UK

Multiple Multilocus DNA Barcodes from the Plastid Genome Discriminate Plant Species Equally Well

A universal barcode system for land plants would be a valuable resource, with potential utility in fields as diverse as ecology, floristics, law enforcement and industry. However, the application of plant barcoding has been constrained by a lack of consensus regarding the most variable and technically practical DNA region(s). We compared eight candidate plant barcoding regions from the plastome and one from the mitochondrial genome for how well they discriminated the monophyly of 92 species in 32 diverse genera of land plants (N = 251 samples). The plastid markers comprise portions of five coding (rpoB, rpoC1, rbcL, matK and 23S rDNA) and three non-coding (trnH-psbA, atpF–atpH, and psbK–psbI) loci. Our survey included several taxonomically complex groups, and in all cases we examined multiple populations and species. The regions differed in their ability to discriminate species, and in ease of retrieval, in terms of amplification and sequencing success. Single locus resolution ranged from 7% (23S rDNA) to 59% (trnH-psbA) of species with well-supported monophyly. Sequence recovery rates were related primarily to amplification success (85–100% for plastid loci), with matK requiring the greatest effort to achieve reasonable recovery (88% using 10 primer pairs). Several loci (matK, psbK–psbI, trnH-psbA) were problematic for generating fully bidirectional sequences. Setting aside technical issues related to amplification and sequencing, combining the more variable plastid markers provided clear benefits for resolving species, although with diminishing returns, as all combinations assessed using four to seven regions had only marginally different success rates (69–71%; values that were approached by several two- and three-region combinations). This performance plateau may indicate fundamental upper limits on the precision of species discrimination that is possible with DNA barcoding systems that include moderate numbers of plastid markers. Resolution to the contentious debate on plant barcoding should therefore involve increased attention to practical issues related to the ease of sequence recovery, global alignability, and marker redundancy in multilocus plant DNA barcoding systems

Ethnic-Racial Socialization in Early Childhood: The Implications of Color-Consciousness and Colorblindness for Prejudice Development

This chapter outlines how early childhood teachers can bring children into conversations surrounding race and racism by drawing on literature on how parents of color discuss these topics. Although educators’ practices surrounding race and racism remain largely unexplored, decades of developmental psychological research indicate that parents of color engage in ethnic-racial socialization practices that are beneficial for children (Hughes et al., 2006). The established dimensions of parental ethnic-racial socialization include (1) cultural socialization, or teaching children about their ethnic heritage and instilling ethnic pride; (2) preparation for bias, or teaching children about racism and preparing them to face discrimination; (3) promotion of mistrust, or warning children about the need to distance themselves from other racial groups; and (4) egalitarianism, or emphasizing the similarities between and equality of all races (Hughes et al. 2006). One consideration to take into account from a developmental perspective is that children’s level of cognitive development impacts how they interpret messages about race. This chapter draws a link between parental ethnic-racial socialization and extends this body of work to school settings, with a focus on teachers. The ideologies of colorblindness and color-consciousness are discussed throughout

Variation of selfing rate and inbreeding depression among individuals and across generations within an admixed Cedrus population

[EN] We investigated the variation and short-term evolution of the selfing rate and inbreeding depression (ID) across three generations within a cedar forest that was established from admixture ca 1860. The mean selfing rate was 9.5%, ranging from 0 to 48% among 20 seed trees (estimated from paternally inherited chloroplast DNA). We computed the probability of selfing for each seed and we investigated ID by comparing selfed and outcrossed seeds within progenies, thus avoiding maternal effects. In all progenies, the germination rate was high (88-100%) and seedling mortality was low (0-12%). The germination dynamics differed significantly between selfed and outcrossed seeds within progenies in the founder gene pool but not in the following generations. This transient effect of selfing could be attributed to epistatic interactions in the original admixture. Regarding the seedling growth traits, the ID was low but significant: 8 and 6% for height and diameter growth, respectively. These rates did not vary among generations, suggesting minor gene effects. At this early stage, outcrossed seedlings outcompeted their selfed relatives, but not necessarily other selfed seedlings from other progenies. Thus, purging these slightly deleterious genes may only occur through within-family selection. Processes that maintain a high level of genetic diversity for fitness-related traits among progenies also reduce the efficiency of purging this part of the genetic load. © 2011 Macmillan Publishers Limited All rights reserved. Guardar / Salir Siguiente >This work has been partially supported by Grant PPI-00-04 from the Polytechnic University of Valencia (Spain). We thank B Fady and E Klein as well as two anonymous reviewers for their helpful comments on a previous version of the paper. 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