1,118 research outputs found
Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas.
Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour. The Rapid VAC regimen was well tolerated and largely administered as an out-patient. There was one toxic death which occurred 2 months after high dose melphalan due to a combination of infection and possible anthracycline cardiomyopathy. Stages were, (Intergroup Rhabdomyosarcoma Study (IRS) system) Group, Group II--four patients. Group III--27 patients and Group IV--12 patients; International Society of Paediatric Oncology (SIOP) staging, Stage I--11, Stage II--13, Stage III--7, Stage IV--12. Actuarial survival at 5 years for all stages is 57% and event free survival 44%. For patients with non-metastatic diseases, 62% and 53% respectively. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches
Chaperone-assisted translocation of a polymer through a nanopore
Using Langevin dynamics simulations, we investigate the dynamics of
chaperone-assisted translocation of a flexible polymer through a nanopore. We
find that increasing the binding energy between the chaperone and
the chain and the chaperone concentration can greatly improve the
translocation probability. Particularly, with increasing the chaperone
concentration a maximum translocation probability is observed for weak binding.
For a fixed chaperone concentration, the histogram of translocation time
has a transition from long-tailed distribution to Gaussian distribution with
increasing . rapidly decreases and then almost saturates with
increasing binding energy for short chain, however, it has a minimum for longer
chains at lower chaperone concentration. We also show that has a minimum
as a function of the chaperone concentration. For different , a
nonuniversal dependence of on the chain length is also observed.
These results can be interpreted by characteristic entropic effects for
flexible polymers induced by either crowding effect from high chaperone
concentration or the intersegmental binding for the high binding energy.Comment: 10 pages, to appear in J. Am. Chem. So
Directed motion emerging from two coupled random processes: Translocation of a chain through a membrane nanopore driven by binding proteins
We investigate the translocation of a stiff polymer consisting of M monomers
through a nanopore in a membrane, in the presence of binding particles
(chaperones) that bind onto the polymer, and partially prevent backsliding of
the polymer through the pore. The process is characterized by the rates: k for
the polymer to make a diffusive jump through the pore, q for unbinding of a
chaperone, and the rate q kappa for binding (with a binding strength kappa);
except for the case of no binding kappa=0 the presence of the chaperones give
rise to an effective force that drives the translocation process. Based on a
(2+1) variate master equation, we study in detail the coupled dynamics of
diffusive translocation and (partial) rectification by the binding proteins. In
particular, we calculate the mean translocation time as a function of the
various physical parameters.Comment: 22 pages, 5 figures, IOP styl
Translocation of structured polynucleotides through nanopores
We investigate theoretically the translocation of structured RNA/DNA
molecules through narrow pores which allow single but not double strands to
pass. The unzipping of basepaired regions within the molecules presents
significant kinetic barriers for the translocation process. We show that this
circumstance may be exploited to determine the full basepairing pattern of
polynucleotides, including RNA pseudoknots. The crucial requirement is that the
translocation dynamics (i.e., the length of the translocated molecular segment)
needs to be recorded as a function of time with a spatial resolution of a few
nucleotides. This could be achieved, for instance, by applying a mechanical
driving force for translocation and recording force-extension curves (FEC's)
with a device such as an atomic force microscope or optical tweezers. Our
analysis suggests that with this added spatial resolution, nanopores could be
transformed into a powerful experimental tool to study the folding of nucleic
acids.Comment: 9 pages, 5 figure
Outcome of children with resistant and relapsed Hodgkin's disease.
During the period 1974-89, 169 children with Hodgkin's disease were treated in the Paediatric Oncology Units of the Royal Marsden and St Bartholomew's Hospitals. The overall actuarial survival for the whole group was 81% at 10 years. Thirty-five of the 169 children either did not achieve a complete remission or subsequently relapsed. The estimated actuarial survival from initial relapse or failure of primary treatment was 60% at 5 years and 45% at 10 years. Over half of the patients requiring salvage therapy had declared themselves within 2 years and only 3 relapses occurred more than 3 years from diagnosis. Very few patients remain disease free long term after failure of primary and initial salvage therapy. Patients relapsing within a year of diagnosis or not achieving a complete response to primary therapy and those with disseminated relapse had a poor response to salvage therapy. A significant subgroup of patients had prolonged survival despite multiple relapses. Neither initial histology nor stage affected survival from relapse although numbers in each subgroup were small
Cetaceans of the Saya de Malha bank region, Indian Ocean: A candidate Important Marine Mammal Area
This is the final version. Available from Elsevier via the DOI in this record. Data availability:
Data will be made available on requestThe banks of Saya de Malha and the surrounding Mascarene Plateau in the Indian Ocean are among the least studied shallow sea water regions in the world. The steep sloping bathymetry of this region is thought to drive high levels of primary productivity and support a diverse range of marine species. Until now, no surveys for cetaceans have been conducted in the waters surrounding Saya de Malha, and so the diversity of cetaceans is unknown. Opportunistic visual and acoustic surveys for cetaceans were conducted onboard a platform of opportunity, the MY Arctic Sunrise, which was involved in a wider project to document the marine life in the region. Survey effort was conducted over 7,700 km, with twelve species of cetacean encountered, including Bryde's, sperm, beaked and killer whales, along with spinner, striped, pantropical spotted and bottlenose dolphins. A match of a sperm whale coda vocalisation to another, well-studied population off the coast of Mauritius suggests possible connectivity between these regions although further data would be required to confirm this. The banks of Saya de Malha appear to support a diverse range of cetacean species and further systematic surveys are required to increase our understanding of how different species utilise the banks. We provide whistle contours from visually confirmed acoustic detections to contribute towards building a region-specific whistle classifier. Given the diversity of species detected in the region, we suggest that the Saya de Malha bank area be designated, either as an Important Marine Mammal Area or as a marine protected area.Greenpeace Internationa
'VEEP' in children with Hodgkin's disease--a regimen to decrease late sequelae.
In an attempt to decrease the risk of second malignancies and future infertility in children with Hodgkin's disease (HD) while retaining acceptable remission rates, an anthracycline based regimen containing no alkylating agent has been devised. VEEP contains vincristine, epirubicin, etoposide and prednisolone given at 3 weekly intervals. Forty-four patients, aged 2-15 years, have been treated: ten relapsed patients and 34 previously untreated with chemotherapy (including three relapsed stage I treated initially with radiotherapy). The median follow up for all patients is 25 months (range 6-52 months). The response rate in previously treated patients was 80% (95% CI 44-97%) and five remain alive in remission. The response rate in untreated patients was 88% (95% CI 72-97%) with 62% CR + CR(u) (uncertain/unconfirmed) (95% CI 44-77%). Of four patients who had a final response of CR(u) three have relapsed at 9, 16 and 38 months. Two of the children in CR have relapsed at 6 and 16 months. The relapse free rate at 3 years is 67% (95% CI 17-82%). In this pilot study the event free survival appears somewhat poorer than conventional combinations and further follow up is required to confirm the salvagability of relapsed patients
Driven polymer translocation through a nanopore: a manifestation of anomalous diffusion
We study the translocation dynamics of a polymer chain threaded through a
nanopore by an external force. By means of diverse methods (scaling arguments,
fractional calculus and Monte Carlo simulation) we show that the relevant
dynamic variable, the translocated number of segments , displays an {\em
anomalous} diffusive behavior even in the {\em presence} of an external force.
The anomalous dynamics of the translocation process is governed by the same
universal exponent , where is the Flory
exponent and - the surface exponent, which was established recently
for the case of non-driven polymer chain threading through a nanopore. A closed
analytic expression for the probability distribution function , which
follows from the relevant {\em fractional} Fokker - Planck equation, is derived
in terms of the polymer chain length and the applied drag force . It is
found that the average translocation time scales as . Also the corresponding time dependent
statistical moments, and reveal unambiguously the anomalous nature of the translocation
dynamics and permit direct measurement of in experiments. These
findings are tested and found to be in perfect agreement with extensive Monte
Carlo (MC) simulations.Comment: 6 pages, 4 figures, accepted to Europhys. Lett; some references were
supplemented; typos were correcte
A novel, fast, HMM-with-Duration implementation – for application with a new, pattern recognition informed, nanopore detector
<p>Abstract</p> <p>Background</p> <p>Hidden Markov Models (HMMs) provide an excellent means for structure identification and feature extraction on stochastic sequential data. An HMM-with-Duration (HMMwD) is an HMM that can also exactly model the hidden-label length (recurrence) distributions – while the regular HMM will impose a best-fit geometric distribution in its modeling/representation.</p> <p>Results</p> <p>A Novel, Fast, HMM-with-Duration (HMMwD) Implementation is presented, and experimental results are shown that demonstrate its performance on two-state synthetic data designed to model Nanopore Detector Data. The HMMwD experimental results are compared to (i) the ideal model and to (ii) the conventional HMM. Its accuracy is clearly an improvement over the standard HMM, and matches that of the ideal solution in many cases where the standard HMM does not. Computationally, the new HMMwD has all the speed advantages of the conventional (simpler) HMM implementation. In preliminary work shown here, HMM feature extraction is then used to establish the first pattern recognition-informed (PRI) sampling control of a Nanopore Detector Device (on a "live" data-stream).</p> <p>Conclusion</p> <p>The improved accuracy of the new HMMwD implementation, at the same order of computational cost as the standard HMM, is an important augmentation for applications in gene structure identification and channel current analysis, especially PRI sampling control, for example, where speed is essential. The PRI experiment was designed to inherit the high accuracy of the well characterized and distinctive blockades of the DNA hairpin molecules used as controls (or blockade "test-probes"). For this test set, the accuracy inherited is 99.9%.</p
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