The atmospheric neutrino flavour ratio measured using a 1.52 kton-year exposure of Soudan 2 is found to be 0.72 ± 0.19
−0.07
+0.05 relative to the expected value from a Monte Carlo calculation. The ...possible background of interactions of neutrons and photons produced in muon interactions in the rock surrounding the detector has been investigated and is shown not to produce low values of the ratio.
An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO), offers timely clinical direction to ASCO's oncologists following publication or presentation of potentially ...practice-changing data from major studies. This PCO addresses the utility of KRAS gene mutation testing in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MoAb) therapy with cetuximab or panitumumab (see Note).
Recent results from phase II and III clinical trials demonstrate that patients with metastatic colorectal cancer benefit from therapy with monoclonal antibodies directed against the EGFR, when used either as monotherapy or combined with chemotherapy. Retrospective subset analyses of the data from these trials strongly suggest that patients who have KRAS mutations detected in codon 12 or 13 do not benefit from this therapy.
Five randomized controlled trials of cetuximab or panitumumab have evaluated outcomes for patients with metastatic colorectal carcinoma in relation to KRAS mutational status as no mutation detected (wild type) or abnormal (mutated). Another five single-arm studies have retrospectively evaluated tumor response according to KRAS status.
Based on systematic reviews of the relevant literature, all patients with metastatic colorectal carcinoma who are candidates for anti-EGFR antibody therapy should have their tumor tested for KRAS mutations in a CLIA-accredited laboratory. If KRAS mutation in codon 12 or 13 is detected, then patients with metastatic colorectal carcinoma should not receive anti-EGFR antibody therapy as part of their treatment.
ASCO's provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written, and are intended to assist physicians in clinical decision-making and identify questions and settings for further research. Due to the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical practice and cannot be assumed to apply to the use of these interventions in the context of clinical trials. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions.
Galectin-3 is a beta-galactoside-binding protein which regulates many biological processes including cell adhesion, migration, cell growth, tumor progression, metastasis, and apoptosis. Although the ...exact function of galectin-3 in cancer development is unclear, galectin-3 expression is associated with neoplastic progression and metastatic potential. Since studies have suggested that tumor cell survival in microcirculation determines the metastatic outcome, we examined the effect of galectin-3 overexpression in human breast carcinoma cell survival using the liver ischemia/reperfusion metastasis model. While the majority of control cells died by hepatic ischemia/reoxygenation, nearly all of galectin-3 overexpressing cells survived. We showed that galectin-3 inhibits nitrogen free radical-mediated apoptosis, one of the major death pathways induced during hepatic ischemia/reperfusion. Galectin-3 inhibition of apoptosis involved protection of mitochondrial integrity, inhibition of cytochrome c release and caspase activation. Taking these results together with the previous observation that galectin-3 inhibits apoptosis induced by loss of cell adhesion, we propose that galectin-3 is a critical determinant for anchorage-independent and free radical-resistant cell survival during metastasis.
A shadow of the Moon, with a statistical significance of 5{sigma}, has been observed in the underground muon flux at a depth of 2090 mwe using the Soudan 2 detector. The angular resolution of the ...detector is well described by a Gaussian with a sigma {<=}0.3 degree sign . The position of the shadow confirms that the alignment of the detector is known to better than 0.15 degree sign and has remained stable during ten years of data taking. (c) 2000 The American Physical Society.
We present the first direct measurements of the pion valence-quark momentum distribution which is related to the square of the pion light-cone wave function. The measurements were carried out using ...data on diffractive dissociation of 500 GeV/c pi(-) into dijets from a platinum target at Fermilab experiment E791. The results show that the /q&q> light-cone asymptotic wave function describes the data well for Q2 approximately 10 (GeV/c)(2) or more. We also measured the transverse momentum distribution of the diffractive dijets.
Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent ...tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.
Summary Background Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of ...adjunctive vitamin D on sputum culture conversion are absent. Methods We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D3 or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for Taq I and Fok I polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D3 . This trial is registered with ClinicalTrials.gov number NCT00419068. Findings 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90–2·16; p=0.14). Taq I genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (pinteraction =0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36–48·01; p=0·02). Fok I genotype did not modify the effect of vitamin D supplementation (pinteraction =0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6–88·2; p<0·0001). Interpretation Administration of four doses of 2·5 mg vitamin D3 increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism. Funding British Lung Foundation.
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