A single institution experience of streptozocin/fluorouracil combination chemotherapy : a case series

Background The combination chemotherapy regimen of streptozocin and 5-fluorouracil (FU/STZ) has been used for the treatment of metastatic neuroendocrine tumours. Aim The aim of this study was to analyse the use of this regimen in a tertiary oncology referral centre over a 10-year period. Method We retrospectively analysed nine cases from February 2000 to May 2010. Patient demographics, chemotherapy schedule, toxicities, progression-free and overall survival were tabulated for each patient. Result The median progression-free survival was 17 months (range 3-48+ months), and overall survival 31 months (range 12-53+ months) with no toxicity related deaths. Conclusion FU/STZ was a well-tolerated regimen that produced significant benefit in the setting of metastatic and progressive disease. Our case series demonstrated comparable progression-free survival and overall survival in relation to randomized controlled studies and previous case series. © Royal Academy of Medicine in Ireland 2011.

Raising Children in Single-Parent Families

Children from single-parent families fare more poorly on multiple outcomes than those in two-parent families. Most explanations for these differences assume that compromised parenting and parent mental health play a central role. This chapter explores the contribution of a range of factors to the parenting and mental health of single mothers using data from approximately 1000 Australian single mothers with a child aged 4–5 or 8–9 years. The findings show that single mothers are more likely than couple mothers to experience parenting and mental health difficulties; however, they also face heightened adversity in their home and extra-familial environments. Importantly, this comparison of single and couple mothers facing similar levels of adversity shows no difference in poor parenting practices, although single mothers remain more vulnerable to psychological distress. These findings have policy implications since they challenge the prevailing view that single-parent families inherently provide sub-optimal environments for raising children.

A multi-genome analysis approach enables tracking of the invasion of a single Russian wheat aphid (Diuraphis noxia) clone throughout the New World

This study investigated the population genetics, demographic history and pathway of invasion of the Russian wheat aphid (RWA) from its native range in Central Asia, the Middle East and Europe to South Africa and the Americas. We screened microsatellite markers, mitochondrial DNA and endosymbiont genes in 504 RWA clones from nineteen populations worldwide. Following pathway analyses of microsatellite and endosymbiont data, we postulate that Turkey and Syria were the most likely sources of invasion to Kenya and South Africa, respectively. Furthermore, we found that one clone transferred between South Africa and the Americas was most likely responsible for the New World invasion. Finally, endosymbiont DNA was found to be a high resolution population genetic marker, extremely useful for studies of invasion over a relatively short evolutionary history time frame. This study has provided valuable insights into the factors that may have facilitated the recent global invasion by this damaging pest.

The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells

Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous system associated with a median survival time of 15 months, even with aggressive therapy. This rapid progression is due in part to diffuse infiltration of single tumor cells into the brain parenchyma, which is thought to involve aberrant interactions between tumor cells and the extracellular matrix (ECM). Here, we test the hypothesis that mechanical cues from the ECM contribute to key tumor cell properties relevant to invasion. We cultured a series of glioma cell lines (U373-MG, U87-MG, U251-MG, SNB19, C6) on fibronectin-coated polymeric ECM substrates of defined mechanical rigidity and investigated the role of ECM rigidity in regulating tumor cell structure, migration, and proliferation. On highly rigid ECMs, tumor cells spread extensively, form prominent stress fibers and mature focal adhesions, and migrate rapidly. As ECM rigidity is lowered to values comparable with normal brain tissue, tumor cells appear rounded and fail to productively migrate. Remarkably, cell proliferation is also strongly regulated by ECM rigidity, with cells dividing much more rapidly on rigid than on compliant ECMs. Pharmacologic inhibition of nonmuscle myosin II–based contractility blunts this rigidity-sensitivity and rescues cell motility on highly compliant substrates. Collectively, our results provide support for a novel model in which ECM rigidity provides a transformative, microenvironmental cue that acts through actomyosin contractility to regulate the invasive properties of GBM tumor cells.

Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden

Over 80% of women diagnosed with advanced-stage ovarian cancer die as a result of disease recurrence due to failure of chemotherapy treatment. In this study, using two distinct ovarian cancer cell lines (epithelial OVCA 433 and mesenchymal HEY) we demonstrate enrichment in a population of cells with high expression of CSC markers at the protein and mRNA levels in response to cisplatin, paclitaxel and the combination of both. We also demonstrate a significant enhancement in the sphere forming abilities of ovarian cancer cells in response to chemotherapy drugs. The results of these in vitro findings are supported by in vivo mouse xenograft models in which intraperitoneal transplantation of cisplatin or paclitaxel-treated residual HEY cells generated significantly higher tumor burden compared to control untreated cells. Both the treated and untreated cells infiltrated the organs of the abdominal cavity. In addition, immunohistochemical studies on mouse tumors injected with cisplatin or paclitaxel treated residual cells displayed higher staining for the proliferative antigen Ki67, oncogeneic CA125, epithelial E-cadherin as well as cancer stem cell markers such as Oct4 and CD117, compared to mice injected with control untreated cells. These results suggest that a short-term single treatment of chemotherapy leaves residual cells that are enriched in CSC-like traits, resulting in an increased metastatic potential. The novel findings in this study are important in understanding the early molecular mechanisms by which chemoresistance and subsequent relapse may be triggered after the first line of chemotherapy treatment.

Single-cell force spectroscopy, an emerging tool to quantify cell adhesion to biomaterials

Cell adhesion receptors play a central role in sensing and integrating signals provided by the cellular environment. Thus, understanding adhesive interactions at the cell-biomaterial interface is essential to improve the design of implants that should emulate certain characteristics of the cell's natural environment. Numerous cell adhesion assays have been developed; among these, atomic force microscopy-based single-cell force spectroscopy (AFM-SCFS) provides a versatile tool to quantify cell adhesion at physiological conditions. Here we discuss how AFM-SCFS can be used to quantify the adhesion of living cells to biomaterials and give examples of using AFM-SCFS in tissue engineering and regenerative medicine. We anticipate that in the near future, AFM-SCFS will be established in the biomaterial field as an important technique to quantify cell-biomaterial interactions and thereby will contribute to the optimization of implants, scaffolds, and medical devices.

Parameterization and reliability of single-leg balance test assessed with inertial sensors in stroke survivors: a cross-sectional study

Background and purpose There are no published studies on the parameterisation and reliability of the single-leg stance (SLS) test with inertial sensors in stroke patients. Purpose: to analyse the reliability (intra-observer/inter-observer) and sensitivity of inertial sensors used for the SLS test in stroke patients. Secondary objective: to compare the records of the two inertial sensors (trunk and lumbar) to detect any significant differences in the kinematic data obtained in the SLS test. Methods Design: cross-sectional study. While performing the SLS test, two inertial sensors were placed at lumbar (L5-S1) and trunk regions (T7–T8). Setting: Laboratory of Biomechanics (Health Science Faculty - University of Málaga). Participants: Four chronic stroke survivors (over 65 yrs old). Measurement: displacement and velocity, Rotation (X-axis), Flexion/Extension (Y-axis), Inclination (Z-axis); Resultant displacement and velocity (V): RV=(Vx2+Vy2+Vz2)−−−−−−−−−−−−−−−−−√ Along with SLS kinematic variables, descriptive analyses, differences between sensors locations and intra-observer and inter-observer reliability were also calculated. Results Differences between the sensors were significant only for left inclination velocity (p = 0.036) and extension displacement in the non-affected leg with eyes open (p = 0.038). Intra-observer reliability of the trunk sensor ranged from 0.889-0.921 for the displacement and 0.849-0.892 for velocity. Intra-observer reliability of the lumbar sensor was between 0.896-0.949 for the displacement and 0.873-0.894 for velocity. Inter-observer reliability of the trunk sensor was between 0.878-0.917 for the displacement and 0.847-0.884 for velocity. Inter-observer reliability of the lumbar sensor ranged from 0.870-0.940 for the displacement and 0.863-0.884 for velocity. Conclusion There were no significant differences between the kinematic records made by an inertial sensor during the development of the SLS testing between two inertial sensors placed in the lumbar and thoracic regions. In addition, inertial sensors. Have the potential to be reliable, valid and sensitive instruments for kinematic measurements during SLS testing but further research is needed.

Pyroxene thermometry of rhyolite lavas of the Bruneau–Jarbidge eruptive center, Central Snake River Plain

The Bruneau–Jarbidge eruptive center of the central Snake River Plain in southern Idaho, USA produced multiple rhyolite lava flows with volumes of <10 km³ to 200 km³ each from ~11.2 to 8.1 Ma, most of which follow its climactic phase of large-volume explosive volcanism, represented by the Cougar Point Tuff, from 12.7 to 10.5 Ma. These lavas represent the waning stages of silicic volcanism at a major eruptive center of the Yellowstone hotspot track. Here we provide pyroxene compositions and thermometry results from several lavas that demonstrate that the demise of the silicic volcanic system was characterized by sustained, high pre-eruptive magma temperatures (mostly ≥950 °C) prior to the onset of exclusively basaltic volcanism at the eruptive center. Pyroxenes display a variety of textures in single samples, including solitary euhedral crystals as well as glomerocrysts, crystal clots and annealed microgranular inclusions of pyroxene ±magnetite± plagioclase. Pigeonite and augite crystals are unzoned, and there are no detectable differences in major and minor element compositions according to textural variety — mineral compositions in the microgranular inclusions and crystal clots are identical to those of phenocrysts in the host lavas. In contrast to members of the preceding Cougar Point Tuff that host polymodal glass and mineral populations, pyroxene compositions in each of the lavas are characterized by single rather than multiple discrete compositional modes. Collectively, the lavas reproduce and extend the range of Fe–Mg pyroxene compositional modes observed in the Cougar Point Tuff to more Mg-rich varieties. The compositionally homogeneous populations of pyroxene in each of the lavas, as well as the lack of core-to-rim zonation in individual crystals suggest that individual eruptions each were fed by compositionally homogeneous magma reservoirs, and similarities with the Cougar Point Tuff suggest consanguinity of such reservoirs to those that supplied the polymodal Cougar Point Tuff. Pyroxene thermometry results obtained using QUILF equilibria yield pre-eruptive magma temperatures of 905 to 980 °C, and individual modes consistently record higher Ca content and higher temperatures than pyroxenes with equivalent Fe–Mg ratios in the preceding Cougar Point Tuff. As is the case with the Cougar Point Tuff, evidence for up-temperature zonation within single crystals that would be consistent with recycling of sub- or near-solidus material from antecedent magma reservoirs by rapid reheating is extremely rare. Also, the absence of intra-crystal zonation, particularly at crystal rims, is not easily reconciled with cannibalization of caldera fill that subsided into pre-eruptive reservoirs. The textural, compositional and thermometric results rather are consistent with minor re-equilibration to higher temperatures of the unerupted crystalline residue from the explosive phase of volcanism, or perhaps with newly generated magmas from source materials very similar to those for the Cougar Point Tuff. Collectively, the data suggest that most of the pyroxene compositional diversity that is represented by the tuffs and lavas was produced early in the history of the eruptive center and that compositions across this range were preserved or duplicated through much of its lifetime. Mineral compositions and thermometry of the multiple lavas suggest that unerupted magmas residual to the explosive phase of volcanism may have been stored at sustained, high temperatures subsequent to the explosive phase of volcanism. If so, such persistent high temperatures and large eruptive magma volumes likewise require an abundant and persistent supply of basalt magmas to the lower and/or mid-crust, consistent with the tectonic setting of a continental hotspot.

Genetic population structure of red snappers (Lutjanus malabaricus Bloch & Schneider, 1801 and Lutjanus erythropterus Bloch, 1790) in central and eastern Indonesia and northern Australia

The genetic population structure of red snapper Lutjanus malabaricus and Lutjanus erythropterus in eastern Indonesia and northern Australia was investigated by allozyme electrophoresis and sequence variation in the control region of mtDNA. Samples were collected from eight sites in Indonesia and four sites in northern Australia for both species. A total of 13 allozyme loci were scored. More variable loci were observed in L. malabaricus than in L. erythropterus. Sequence variation in the control region (left domain) of the mitochondrial genome was assessed by RFLP and direct sequencing. MtDNA haplotype diversity was high (L. erythropterus, 0.95 and L. malabaricus, 0.97), as was intraspecific sequence divergence, (L. erythropterus, 0.0-12.5% and L. malabaricus, 0.0-9.5%). The pattern of mtDNA haplotype frequencies grouped both species into two broad fisheries stocks with a genetic boundary either between Kupang and Sape (L. malabaricus) or between Kupang and Australian Timor Sea (L. erythropertus). The allozyme analyses revealed similar boundaries for L. erythropterus. Seven allozymes stocks compared to two mtDNA stocks of L. malabaricus including Ambon, which was not sampled with mtDNA, however, were reported. Possible reasons for differences in discrimination between the methods include: i) increased power of multiple allozyme loci over the single mtDNA locus, ii) insufficient gene sampling in the mtDNA control region and iii) relative evolutionary dynamics of nuclear (allozyme loci) and mitochondrial DNA in these taxa. Allozyme and haplotype data did not distinguish separate stocks among the four Australian locations nor the central Indonesian (Bali and Sape locations) for both L. malabaricus and L. erythropterus.

A high-density consensus map of barley linking DArT markers to SSR, RFLP and STS loci and agricultural traits

Background: Molecular marker technologies are undergoing a transition from largely serial assays measuring DNA fragment sizes to hybridization-based technologies with high multiplexing levels. Diversity Arrays Technology (DArT) is a hybridization-based technology that is increasingly being adopted by barley researchers. There is a need to integrate the information generated by DArT with previous data produced with gel-based marker technologies. The goal of this study was to build a high-density consensus linkage map from the combined datasets of ten populations, most of which were simultaneously typed with DArT and Simple Sequence Repeat (SSR), Restriction Enzyme Fragment Polymorphism (RFLP) and/or Sequence Tagged Site (STS) markers. Results: The consensus map, built using a combination of JoinMap 3.0 software and several purpose-built perl scripts, comprised 2,935 loci (2,085 DArT, 850 other loci) and spanned 1,161 cM. It contained a total of 1,629 'bins' (unique loci), with an average inter-bin distance of 0.7 ± 1.0 cM (median = 0.3 cM). More than 98% of the map could be covered with a single DArT assay. The arrangement of loci was very similar to, and almost as optimal as, the arrangement of loci in component maps built for individual populations. The locus order of a synthetic map derived from merging the component maps without considering the segregation data was only slightly inferior. The distribution of loci along chromosomes indicated centromeric suppression of recombination in all chromosomes except 5H. DArT markers appeared to have a moderate tendency toward hypomethylated, gene-rich regions in distal chromosome areas. On the average, 14 ± 9 DArT loci were identified within 5 cM on either side of SSR, RFLP or STS loci previously identified as linked to agricultural traits. Conclusion: Our barley consensus map provides a framework for transferring genetic information between different marker systems and for deploying DArT markers in molecular breeding schemes. The study also highlights the need for improved software for building consensus maps from high-density segregation data of multiple populations.

Visualization of enantiomers using natural abundant 13C-filtered single and double quantum selective refocusing experiments: Application to small chiral molecules

The routine use of proton NMR for the visualization of enantiomers, aligned in the chiral liquid crystal solvent poly-γ-benzyl-l-glutamate (PBLG), is restricted due to severe loss of resolution arising from large number of pair wise interaction of nuclear spins. In the present study, we have designed two experimental techniques for their visualization utilizing the natural abundance 13C edited selective refocusing of single quantum (CH-SERF) and double quantum (CH-DQSERF) coherences. The methods achieve chiral discrimination and aid in the simultaneous determination of homonuclear couplings between active and passive spins and heteronuclear couplings between the excited protons and the participating 13C spin. The CH-SERF also overcomes the problem of overlap of central transitions of the methyl selective refocusing (SERF) experiment resulting in better chiral discrimination. Theoretical description of the evolution of magnetization in both the sequences has been discussed using polarization operator formalism.

Median muotoilema : Muotoilun mediajulkisuus suomalaisessa talouslehdistössä

Designed by the Media The Media publicity of Design in the Finnish Economic Press The meaning of design has increased in consumer societies. Design is the subject of debate and the number of media discussions has also increased steadily. Especially the role of industrial design has been emphasised. In this study I examine the media publicity of design in the Finnish economic press from the late 1980s to the beginning of the 2000s. The research question is connected to media representations: How is design represented in the Finnish economic press? In other words, what are the central topics of design in the economic press, and to what issues are the media debates connected? The usually repeated phrase that design discussions take place only on the cultural pages of the daily press or in cultural contexts is being changed. Design is also linked to the consumer culture and consumers everyday practices. The research material has been collected from the Finnish economic press. The qualitative sample consists of articles from Kauppalehti, Taloussanomat and from several economic papers published by the Talentum Corporation. The approach of the research is explorative, descriptive and hermeneutic. This means that the economic press articles are used to explore how design is represented in the media. In addition, the characteristics of design represented in the media are described in detail. The research is based on the interpretive tradition of studying textual materials. Background assumptions are thus grounded in hermeneutics. Erving Goffman s frame analysis is applied in analysing the economic press materials. The frames interpreted from the articles depict the media publicity of design in the Finnish economic press. The research opens up a multidimensional picture of design in the economic press. The analysis resulted in five frames that describe design from various points of view. In the personal frame designers are described in private settings and through their personal experiences. The second frame relates to design work. In the frame of mastery of the profession, the designers work is interpreted widely. Design is considered from the aspects of controlling personal know-how, co-operation and the overall process of design. The third frame is connected to the actual substance of the economic press. In the frame of economy and market, design is linked to international competitiveness, companies competitive advantage and benefit creation for the consumers. The fourth frame is connected to the actors promoting design on a societal level. In the communal frame, the economic press describes design policy, design research and education and other actors that actively develop design in the societal networks. The last frame is linked to the traditions of design and above all to the examination of the cultural transition. In the frame of culture the traditions of design are emphasised. Design is also connected to the industrial culture and furthermore to the themes of the consumer culture. It can be argued that the frames construct media publicity of design from various points of view. The frames describe situations, action and the actors of design. The interpreted media frames make it possible to understand the relation of interpreted design actions and the culture. Thus, media has a crucial role in representing and recreating meanings related to design. The publicity of design is characterised by the five focal themes: personification, professionalisation, commercialisation, communalisation and transition of cultural focus from the traditions of design to the industrial culture and the consumer culture. Based on my interpretation these themes are guided by the mediatisation of design. The design phenomenon is defined more often on the basis of the media representations in the public discourses. The design culture outlined in this research connects socially constructed and structurally organised action. Socially constructed action in design is connected to the experiences, social recreation and collective development of design. Structurally, design is described as professional know-how, as a process and as an economic profit generating action in the society. The events described by the media affect the way in which people experience the world, the meanings they connect to the events around themselves and their life in the world. By affecting experiences, the media indirectly affects human actions. People have become habituated to read media representations on a daily basis, but they are not used to reading and interpreting the various meanings that are incorporated in the media texts.

Ultrafast Switching Time and Third Order Nonlinear Coefficients of Microwave Treated Single Walled Carbon Nanotube Suspensions

Microwave treated water soluble and amide functionalized single walled carbon nanotubes have been investigated using femtosecond degenerate pump-probe and nonlinear transmission experiments. The time resolved differential transmission using 75 femtosecond pulse with the central wavelength of 790 nm shows a bi-exponential ultrafast photo-bleaching with time constants of 160 fs (130 fs) and 920 fs (300 fs) for water soluble (amide functionalized) nanotubes. Open and closed aperture z-scans show saturation absorption and positive (negative) nonlinear refraction for water soluble (amide functionalized) nanotubes. Two photon absorption coefficient, beta(0) similar to 250 cm/GW (650 cm/GW) and nonlinear index, gamma similar to 15 cm(2)/pW (-30 cm(2)/pW) are obtained from the theoretical fit in the saturation limit to the data for two types of nanotubes.

Floristic composition and pasture condition of Aristida/Bothriochloa pastures in central Queensland. II. Soil and pasture condition interactions

Sustainable management of native pastures requires an understanding of what the bounds of pasture composition, cover and soil surface condition are for healthy pastoral landscapes to persist. A survey of 107 Aristida/Bothriochloa pasture sites in inland central Queensland was conducted. The sites were chosen for their current diversity of tree cover, apparent pasture condition and soil type to assist in setting more objective bounds on condition ‘states’ in such pastures. Assessors’ estimates of pasture condition were strongly correlated with herbage mass (r = 0.57) and projected ground cover (r = 0. 58), and moderately correlated with pasture crown cover (r = 0.35) and tree basal area (r = 0.32). Pasture condition was not correlated with pasture plant density or the frequency of simple guilds of pasture species. The soil type of Aristida/Bothriochloa pasture communities was generally hard-setting, low in cryptogam cover but moderately covered with litter and projected ground cover (30–50%). There was no correlation between projected ground cover of pasture and estimated ground-level cover of plant crowns. Tree basal area was correlated with broad categories of soil type, probably because greater tree clearing has occurred on the more fertile, heavy-textured clay soils. Of the main perennial grasses, some showed strong soil preferences, for example Tripogon loliiformis for hard-setting soils and Dichanthium sericeum for clays. Common species, such as Chrysopogon fallax and Heteropogon contortus, had no strong soil preference. Wiregrasses (Aristida spp.) tended to be uncommon at both ends of the estimated pasture condition scale whereas H. contortus was far more common in pastures in good condition. Sedges (Cyperaceae) were common on all soil types and for all pasture condition ratings. Plants identified as increaser species were Tragus australianus, daisies (Asteraceae) and potentially toxic herbaceous legumes such as Indigofera spp. and Crotalaria spp. Pasture condition could not be reliably predicted based on the abundance of a single species or taxon but there may be scope for using integrated data for four to five ecologically contrasting plants such as Themeda triandra with daisies, T. loliiformis and flannel weeds (Malvaceae).

Floristic composition and pasture condition of Aristida/Bothriochloa pastures in central Queensland. I. Pasture floristics

A survey was conducted in central inland Queensland, Australia of 108 sites that were deemed to contain Aristida/Bothriochloa native pastures to quantitatively describe the pastures and attempt to delineate possible sub-types. The pastures were described in terms of their floristic composition, plant density and crown cover. There were generally ~20 (range 5–33) main pasture species at a site. A single dominant perennial grass was rare with three to six prominent species the norm. Chrysopogon fallax (golden-beard grass) was the perennial grass most consistently found in all pastures whereas Aristida calycina (dark wiregrass), Enneapogon spp. (bottlewasher grasses), Brunoniella australis (blue trumpet) and Panicum effusum (hairy panic) were all regularly present. The pastures did not readily separate into broad floristic sub-groups, but three groups that landholders could recognise from a combination of the dominant tree and soil type were identified. The three groups were Eucalyptus crebra (narrow-leaved ironbark), E. melanophloia (silver-leaved ironbark) and E. populnea (poplar box). The pastures of the three main sub-groups were then characterised by the prominent presence, singly or in combination, of Bothriochloa ewartiana (desert bluegrass), Eremochloa bimaculata (poverty grass), Bothriochloa decipiens (pitted bluegrass) or Heteropogon contortus (black speargrass). The poplar box group had the greatest diversity of prominent grasses whereas the narrow-leaved ironbark group had the least. Non-native Cenchrus ciliaris (buffel grass) and Melinis repens (red Natal grass) were generally present at low densities. Describing pastures in terms of frequency of a few species or species groups sometimes failed to capture the true nature of the pasture but plant abundance for most species, as density, herbage mass of dry matter or plant crown cover, was correlated with its recorded frequency. A quantitative description of an average pasture in fair condition is provided but it was not possible to explain why some species often occur together or fail to co-exist in Aristida/Bothriochloa pastures, for example C. ciliaris and E. bimaculata rarely co-exist whereas Tragus australianus (small burrgrass) and Enneapogon spp. are frequently recorded together. Most crown cover was provided by perennial grasses but many of these are Aristida spp. (wiregrasses) and not regarded as useful forage for livestock. No new or improved categorisation of the great variation evident in the Aristida/Bothriochloa native pasture type can be given despite the much improved detail provided of the floristic composition by this survey.