1,046 research outputs found
Minimax Rates for Nonparametric Specification Testing in Regression Models
We deal with the issue of testing the specification of a regression function. As a leading case, we consider testing for a pure noise model. We study the smallest local alternatives that can be detected asymptotically in a minimax sense. We propose a simple testing procedure that has asymptotic optimal minimax properties for regular alternatives. We then adapt this procedure to testing the specification of a nonlinear parametric regression model. As a by-product, we obtain the rate of the optimal smoothing parameter that ensures optimal minimax properties for the test. We show that, by contrast, non-smoothing tests, such as Bierens' (1982) integrated conditional moment test, have undesirable minimax properties.
Role of brachytherapy in the treatment of cancers of the anal canal. Long-term follow-up and multivariate analysis of a large monocentric retrospective series.
BACKGROUND AND PURPOSE: There are few data on long-term clinical results and tolerance of brachytherapy in anal canal cancer. We present one of the largest retrospective analyses of anal canal cancers treated with external beam radiotherapy with/without (±) chemotherapy followed by a brachytherapy boost.
MATERIALS AND METHODS: We performed a retrospective analysis of clinical results in terms of efficacy and toxicity. The impact of different clinical and therapeutic variables on these outcomes was studied.
RESULTS: From May 1992 to December 2009, 209 patients received brachytherapy after external beam radiotherapy ± chemotherapy. Of these patients, 163 were stage II or stage IIIA (UICC 2002) and 58 were N1-3. According to age, ECOG performance status (PS), and comorbidities, patients received either radiotherapy alone (58/209) or radiochemotherapy (151/209). The median follow-up was 72.8 months. The 5- and 10-year local control rates were 78.6 and 73.9â%, respectively. Globally, severe acute and late G3-4 reactions (NCI-CTC scale v. 4.0) occurred in 11.2 and 6.3â% of patients, respectively. Univariate analysis showed the statistical impact of the pelvic treatment volume (pâ=â0.046) and of the total dose (pâ=â0.02) on the risk of severe acute and late toxicities, respectively. Only six patients required permanent colostomy because of severe late anorectal toxicities.
CONCLUSION: After a long follow-up time, brachytherapy showed an acceptable toxicity profile and high local control rates in patients with anal canal cancer
Charge and current-sensitive preamplifiers for pulse shape discrimination techniques with silicon detectors
New charge and current-sensitive preamplifiers coupled to silicon detectors
and devoted to studies in nuclear structure and dynamics have been developed
and tested. For the first time shapes of current pulses from light charged
particles and carbon ions are presented. Capabilities for pulse shape
discrimination techniques are demonstrated.Comment: 14 pages, 12 figures, to be published in Nucl. Inst. Meth.
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The programming of sequences of saccades
Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle
The seasonal cycle of ocean-atmosphere CO2 Flux in Ryder Bay, West Antarctic Peninsula
Approximately 15 million km2 of the Southern Ocean is seasonally ice covered, yet the processes affecting carbon cycling and gas exchange in this climatically important region remain inadequately understood. Here, 3 years of dissolved inorganic carbon (DIC) measurements and carbon dioxide (CO2) fluxes from Ryder Bay on the west Antarctic Peninsula (WAP) are presented. During spring and summer, primary production in the surface ocean promotes atmospheric CO2 uptake. In winter, higher DIC, caused by net heterotrophy and vertical mixing with Circumpolar Deep Water, results in outgassing of CO2 from the ocean. Ryder Bay is found to be a net sink of atmospheric CO2 of 0.59â0.94 mol C mâ2 yrâ1 (average of 3 years). Seasonal sea ice cover increases the net annual CO2 uptake, but its effect on gas exchange remains poorly constrained. A reduction in sea ice on the WAP shelf may reduce the strength of the oceanic CO2 sink in this region
Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire
Idiosyncratic adverse drug reactions are unpredictable, dose independent and
potentially life threatening; this makes them a major factor contributing to
the cost and uncertainty of drug development. Clinical data suggest that many
such reactions involve immune mechanisms, and genetic association studies have
identified strong linkage between drug hypersensitivity reactions to several
drugs and specific HLA alleles. One of the strongest such genetic associations
found has been for the antiviral drug abacavir, which causes severe adverse
reactions exclusively in patients expressing the HLA molecular variant B*57:01.
Abacavir adverse reactions were recently shown to be driven by drug-specific
activation of cytokine-producing, cytotoxic CD8+ T cells that required
HLA-B*57:01 molecules for their function. However, the mechanism by which
abacavir induces this pathologic T cell response remains unclear. Here we show
that abacavir can bind within the F-pocket of the peptide-binding groove of
HLA-B*57:01 thereby altering its specificity. This supports a novel explanation
for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can
alter the repertoire of self-peptides presented to T cells thus causing the
equivalent of an alloreactive T cell response. Indeed, we identified specific
self-peptides that are presented only in the presence of abacavir, and that
were recognized by T cells of hypersensitive patients. The assays we have
established can be applied to test additional compounds with suspected HLA
linked hypersensitivities in vitro. Where successful, these assays could speed
up the discovery and mechanistic understanding of HLA linked hypersensitivities
as well as guide the development of safer drugs
Efficient aberrations pre-compensation and wavefront correction with a deformable mirror in the middle of a petawatt-class CPA laser system
AbstractIn this paper, we describe the experimental validation of the technique of correction of wavefront aberration in the middle of the laser amplifying chain. This technique allows the correction of the aberrations from the first part of the laser system, and the pre-compensation of the aberrations built in the second part. This approach will allow an effective aberration management in the laser chain, to protect the optical surfaces and optimize performances, and is the only possible approach for multi-petawatt laser system from the technical and economical point of view. This approach is now possible after the introduction of new deformable mirrors with lower static aberrations and higher dynamic than the standard devices
Cord blood-circulating endothelial progenitors for treatment of vascular diseases
Abstract Adult peripheral blood (PB) endothelial progenitor cells (EPC) are produced in the bone marrow and are able to integrate vascular structures in sites of neoangiogenesis. EPCs thus represent a potential therapeutic tool for ischaemic diseases. However, use of autologous EPCs in cell therapy is limited by their rarity in adult PB. Cord blood (CB) contains more EPCs than PB, and they are functional after expansion. They form primary colonies that give rise to secondary colonies, each yielding more than 10 7 cells after few passages. The number of endothelial cells obtained from one unit of CB is compatible with potential clinical application. EPC colonies can be securely produced, expanded and cryopreserved in close culture devices and endothelial cells produced in these conditions are functional as shown in different in vitro and in vivo assays. As CB EPCderived endothelial cells would be allogeneic to patients, it would be of interest to prepare them from ready-existing CB banks. We show that not all frozen CB units from a CB bank are able to generate EPC colonies in culture, and when they do so, number of colonies is lower than that obtained with fresh CB units. However, endothelial cells derived from frozen CB have the same phenotypical and functional properties than those derived from fresh CB. This indicates that CB cryopreservation should be improved to preserve integrity of stem cells other than haematopoietic ones. Feasibility of using CB for clinical applications will be validated in porcine models of ischaemia. Origin and role of EP
Inhibition of Wnt/ÎČ-Catenin Signaling by a Soluble Collagen-Derived Frizzled Domain Interacting with Wnt3a and the Receptors Frizzled 1 and 8
The Wnt/ÎČ-catenin pathway controls cell proliferation, death and differentiation. Several families of extracellular proteins can antagonize Wnt/ÎČ-catenin signaling, including the decoy receptors known as secreted frizzled related proteins (SFRPs), which have a cysteine-rich domain (CRD) structurally similar to the extracellular Wnt-binding domain of the frizzled receptors. SFRPs inhibit Wnt signaling by sequestering Wnts through the CRD or by forming inactive complexes with the frizzled receptors. Other endogenous molecules carrying frizzled CRDs inhibit Wnt signaling, such as V3Nter, which is proteolytically derived from the cell surface component collagen XVIII and contains a biologically active frizzled domain (FZC18) inhibiting in vivo cell proliferation and tumor growth in mice. We recently showed that FZC18 expressing cells deliver short-range signals to neighboring cells, decreasing their proliferation in vitro and in vivo through the Wnt/ÎČ-catenin signaling pathway. Here, using low concentrations of soluble FZC18 and Wnt3a, we show that they physically interact in a cell-free system. In addition, soluble FZC18 binds the frizzled 1 and 8 receptors' CRDs, reducing cell sensitivity to Wnt3a. Conversely, inhibition of Wnt/ÎČ-catenin signaling was partially rescued by the expression of full-length frizzled 1 and 8 receptors, but enhanced by the expression of a chimeric cell-membrane-tethered frizzled 8 CRD. Moreover, soluble, partially purified recombinant FZC18_CRD inhibited Wnt3a-induced ÎČ-catenin activation. Taken together, the data indicate that collagen XVIII-derived frizzled CRD shifts Wnt sensitivity of normal cells to a lower pitch and controls their growth
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