1,724 research outputs found
Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma
BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre
A mink-free GB:perspectives on eradicating American mink Neovison vison from Great Britain and its islands
CMB Telescopes and Optical Systems
The cosmic microwave background radiation (CMB) is now firmly established as
a fundamental and essential probe of the geometry, constituents, and birth of
the Universe. The CMB is a potent observable because it can be measured with
precision and accuracy. Just as importantly, theoretical models of the Universe
can predict the characteristics of the CMB to high accuracy, and those
predictions can be directly compared to observations. There are multiple
aspects associated with making a precise measurement. In this review, we focus
on optical components for the instrumentation used to measure the CMB
polarization and temperature anisotropy. We begin with an overview of general
considerations for CMB observations and discuss common concepts used in the
community. We next consider a variety of alternatives available for a designer
of a CMB telescope. Our discussion is guided by the ground and balloon-based
instruments that have been implemented over the years. In the same vein, we
compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the
South Pole Telescope (SPT). CMB interferometers are presented briefly. We
conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and
Planck, to demonstrate a remarkable evolution in design, sensitivity,
resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1:
Telescopes and Instrumentatio
Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population
Mineral nutrient malnutrition, and particularly
deficiency in zinc and iron, afflicts over 3 billion people
worldwide. Wild emmer wheat, Triticum turgidum ssp.
dicoccoides, genepool harbors a rich allelic repertoire for
mineral nutrients in the grain. The genetic and physiological
basis of grain protein, micronutrients (zinc, iron,
copper and manganese) and macronutrients (calcium,
magnesium, potassium, phosphorus and sulfur) concentration
was studied in tetraploid wheat population of 152
recombinant inbred lines (RILs), derived from a cross
between durum wheat (cv. Langdon) and wild emmer
(accession G18-16). Wide genetic variation was found
among the RILs for all grain minerals, with considerable
transgressive effect. A total of 82 QTLs were mapped for
10 minerals with LOD score range of 3.2–16.7. Most QTLs
were in favor of the wild allele (50 QTLs). Fourteen pairs
of QTLs for the same trait were mapped to seemingly
homoeologous positions, reflecting synteny between the A
and B genomes. Significant positive correlation was found
between grain protein concentration (GPC), Zn, Fe and Cu,
which was supported by significant overlap between the
respective QTLs, suggesting common physiological and/or
genetic factors controlling the concentrations of these
mineral nutrients. Few genomic regions (chromosomes 2A,
5A, 6B and 7A) were found to harbor clusters of QTLs for
GPC and other nutrients. These identified QTLs may
facilitate the use of wild alleles for improving grain
nutritional quality of elite wheat cultivars, especially in
terms of protein, Zn and Fe
CSAP localizes to polyglutamylated microtubules and promotes proper cilia function and zebrafish development
The diverse populations of microtubule polymers in cells are functionally distinguished by different posttranslational modifications, including polyglutamylation. Polyglutamylation is enriched on subsets of microtubules including those found in the centrioles, mitotic spindle, and cilia. However, whether this modification alters intrinsic microtubule dynamics or affects extrinsic associations with specific interacting partners remains to be determined. Here we identify the microtubule-binding protein centriole and spindle–associated protein (CSAP), which colocalizes with polyglutamylated tubulin to centrioles, spindle microtubules, and cilia in human tissue culture cells. Reducing tubulin polyglutamylation prevents CSAP localization to both spindle and cilia microtubules. In zebrafish, CSAP is required for normal brain development and proper left–right asymmetry, defects that are qualitatively similar to those reported previously for depletion of polyglutamylation-conjugating enzymes. We also find that CSAP is required for proper cilia beating. Our work supports a model in which polyglutamylation can target selected microtubule-associated proteins, such as CSAP, to microtubule subpopulations, providing specific functional capabilities to these populations.National Institutes of Health (U.S.) (Grant no. GM074746)American Cancer Society. Research Scholar Grant (121776)National Institute of General Medical Sciences (U.S.) (GM088313
A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279
It is widely accepted that strong and variable radiation detected over all
accessible energy bands in a number of active galaxies arises from a
relativistic, Doppler-boosted jet pointing close to our line of sight. The size
of the emitting zone and the location of this region relative to the central
supermassive black hole are, however, poorly known, with estimates ranging from
light-hours to a light-year or more. Here we report the coincidence of a
gamma-ray flare with a dramatic change of optical polarization angle. This
provides evidence for co-spatiality of optical and gamma-ray emission regions
and indicates a highly ordered jet magnetic field. The results also require a
non-axisymmetric structure of the emission zone, implying a curved trajectory
for the emitting material within the jet, with the dissipation region located
at a considerable distance from the black hole, at about 10^5 gravitational
radii.Comment: Published in Nature issued on 18 February 2010. Corresponding
authors: Masaaki Hayashida and Greg Madejsk
Acrocephalus orinus: A Case of Mistaken Identity
Recent discovery of the Large-billed Reed Warbler (Acrocephalus orinus) in museums and in the wild significantly expanded our knowledge of its morphological traits and genetic variability, and revealed new data on geographical distribution of the breeding grounds, migration routes and wintering locations of this species. It is now certain that A. orinus is breeding in Central Asia; however, the precise area of distribution remains unclear. The difficulty in the further study of this species lies in the small number of known specimens, with only 13 currently available in museums, and in the relative uncertainty of the breeding area and habitat of this species. Following morphological and genetic analyses from Svensson, et al, we describe 14 new A. orinus specimens from collections of Zoological Museums of the former USSR from the territory of Central Asian states. All of these specimens were erroneously labeled as Blyth's Reed Warbler (A. dumetorum), which is thought to be a breeding species in these areas. The 14 new A. orinus specimens were collected during breeding season while most of the 85 A. dumetorum specimens from the same area were collected during the migration period. Our data indicate that the Central Asian territory previously attributed as breeding grounds of A. dumetorum is likely to constitute the breeding territory of A. orinus. This rare case of a re-description of the breeding territory of a lost species emphasizes the importance of maintenance of museum collections around the world. If the present data on the breeding grounds of A. orinus are confirmed with field observations and collections, the literature on the biology of A. dumetorum from the southern part of its range may have to be reconsidered
Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy
Background
A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets.
Methods
Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis.
Results
A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001).
Conclusion
We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty
Clinical heterogeneity of abnormal glucose homeostasis associated with the HNF4A R311H mutation
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A Search for Dark Higgs Bosons
Recent astrophysical and terrestrial experiments have motivated the proposal
of a dark sector with GeV-scale gauge boson force carriers and new Higgs
bosons. We present a search for a dark Higgs boson using 516 fb-1 of data
collected with the BABAR detector. We do not observe a significant signal and
we set 90% confidence level upper limits on the product of the Standard
Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots
for b/w printin
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