On the treatment of singularities of the Watson Hamiltonian for nonlinear molecules

The applicability of the Watson Hamiltonian for the description of nonlinear molecules—especially triatomic ones—has always been questioned, as the Jacobian of the transformation that leads to the Watson Hamiltonian, vanishes at the linear configuration. This results in singular behavior of the Watson Hamiltonian, giving rise to serious numerical problems in the computation of vibrational spectra, with unphysical, spurious vibrational states appearing among the physical vibrations, especially in the region of highly excited states. In this work, we analyze the problem and propose a simple way to confine the nuclear wavefunction in such a way that the spurious solutions are eliminated. We study the water molecule and observe an improvement compared with previous results. We also apply the method to the van der Walls molecule XeHe2.

Effectiveness of different footbath solutions in the treatment of digital dermatitis in dairy cows

Three experiments were conducted to test the effectiveness of different footbath solutions and regimens in the treatment of digital dermatitis (DD) in dairy cows. During the study, groups of cows walked through allocated footbath solutions after milking on 4 consecutive occasions. All cows were scored weekly for DD lesion stage on the hind feet during milking. A “transition grade” was assigned on the basis of whether the DD lesions improved (1) or deteriorated or did not improve (0) from week to week. This grade per cow was averaged for all cows in the group. In experiment 1, 118 cows were allocated to 1 of 3 footbath treatments for 5 wk: (1) 5% CuSO4 each week, (2) 2% ClO- each week, or (3) no footbath (control). The mean transition grade, and proportion of cows without DD lesions at the end of the trial were significantly higher for treatment 1 above (0.36, 0.13, and 0.11, respectively; standard error of the difference, SED=0.057). In experiment 2, 117 cows were allocated to 1 of 4 footbath treatment regimens for 8 wk: (1) 5% CuSO4 each week, (2) 2% CuSO4 each week, (3) 5% CuSO4 each fortnight, or (4) 2% CuSO4 each fortnight. For welfare reasons, cows allocated to the weekly and fortnightly footbath regimens had an average prevalence of >60% and =25% active DD at the start of the trial, respectively. Significantly more cows had no DD lesions (0.53 vs. 0.36, respectively; SED=0.049), and the mean transition grade of DD lesions was higher in the 5% compared with the 2% weekly CuSO4 treatment (0.52 vs. 0.38, respectively; SED=0.066). Similarly, significantly more cows had no DD lesions in the 5% compared with the 2% fortnightly CuSO4 treatments (0.64 vs. 0.47, respectively; SED=0.049). In experiment 3, 95 cows were allocated to 1 of 3 footbath treatments: (1) each week alternating 5% CuSO4 with 10% salt water, (2) each week alternating 5% CuSO4 with water, or (3) 5% CuSO4 each fortnight (control). After 10 wk, more cows had no DD in the salt water treatment than in the control treatment (0.35 vs. 0.26, respectively; SED=0.038), but levels of active lesions were higher for this treatment than in the other 2 treatments (0.17, 0.00, and 0.13, respectively; SED=0.029). Treatment did not affect mean transition grade of DD lesions. In conclusion, CuSO4 was the only footbath solution that was consistently effective for treatment of DD. In cases when DD prevalence was high, a footbath each week using 5% CuSO4 was the most effective treatment.

Effect of phytoestrogen and antioxidant supplementation on oxidative DNA damage assessed using the comet assay

Antioxidant species may act in vivo to decrease oxidative damage to DNA, protein and lipids thus reducing the risk of coronary heart disease and cancer. Phytoestrogens are plant compounds which are a major component of traditional Asian diets and which may be protective against certain hormone-dependent cancers (breast and prostate) and against coronary heart disease. They may also be able to function as antioxidants, scavenging potentially harmful free radicals. In this study, the effects of the isoflavonoids (a class of phytoestrogen) genistein and equol on hydrogen peroxide-mediated DNA damage in human lymphocytes were determined using alkaline single-cell gel electrophoresis (the comet assay). Treatment with hydrogen peroxide significantly increased the levels of DNA strand breaks. Pre-treatment of the cells with both genistein and equol offered protection against this damage at concentrations within the physiological range. This protection was greater than that offered by addition of the known antioxidant vitamins ascorbic acid and alpha -tocopherol, or the compounds 17 beta -oestradiol and Tamoxifen which have similar structures to isoflavonoids and are known to have weak antioxidant properties. These findings are consistent with the hypothesis that phytoestrogens can, under certain conditions, function as antioxidants and protect against oxidatively-induced DNA damage. (C) 2001 Elsevier Science B.V. All rights reserved.

Long-term occlusal and soft-tissue profile outcomes after treatment of Class II Division 1 malocclusion with fixed appliances

Introduction: Our objective was to determine which factors were predictive of good long-term outcomes after fixed appliance treatment of Class II Division 1 malocclusion. Methods: Two hundred seven patients with Class II Division 1 malocclusion were examined in early adulthood at a mean of 4.6 years after treatment with fixed appliances. The peer assessment rating index was used to evaluate dental alignment and occlusal relationships. The soft-tissue profile was assessed with the Holdaway angle. Results: Logistic regression identified 3 pretreatment variables that were predictive of a good facial profile (Holdaway angle) at recall: the lower lip to E-plane distance (P

Electron-beam treatment of poly(lactic acid) to control degradation profiles

Bioresorbable polymers such as polylactide (PIA) and polylactide-co-glycolide (PLGA) have been used successfully as biomaterials in a wide range of medical applications. However, their slow degradation rates and propensity to lose strength before mass have caused problems. A central challenge for the development of these materials is the assurance of consistent and predictable in vivo degradation. Previous work has illustrated the potential to influence polymer degradation using electron beam (e-beam) radiation. The work addressed in this paper investigates further the utilisation of e-beam radiation in order to achieve a more surface specific effect. Variation of e-beam energy was studied as a means to control the effective penetrative depth in poly-L-lactide (PLEA). PLEA samples were exposed to e-beam radiation at individual energies of 0.5 MeV, 0.75 MeV and 1.5 MeV. The near-surface region of the PLEA samples was shown to be affected by e-beam irradiation with induced changes in molecular weight, morphology, flexural strength and degradation profile. Moreover, the depth to which the physical properties of the polymer were affected is dependent on the beam energy used. Computer modelling of the transmission of each e-beam energy level used corresponded well with these findings. (C) 2010 Elsevier Ltd. All rights reserved.

Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

Background: When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. Methods: COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1·162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. Findings: 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15·8 months (IQR 9·4—26·1) in arm A and 14·4 months (8·0—24·7) in arm C (hazard ratio [HR] 1·084, 80% CI 1·008—1·165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19·6 months (13·0—28·1) in arm A and 18·0 months (12·1—29·3) in arm C (HR 1·087, 0·986—1·198). The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary. Preplanned subgroup analyses in the per-protocol population showed that a raised baseline platelet count, defined as 400 000 per µL or higher (271 [28%] of 978 patients), was associated with poor survival with intermittent chemotherapy: the HR for comparison of arm C and arm A in patients with a normal platelet count was 0·96 (95% CI 0·80—1·15, p=0·66), versus 1·54 (1·17—2·03, p=0·0018) in patients with a raised platelet count (p=0·0027 for interaction). In the per-protocol population, more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects (72 [15%] vs 60 [12%]), whereas nausea and vomiting were more common on intermittent treatment (11 [2%] vs 43 [8%]). Grade 3 or worse peripheral neuropathy (126 [27%] vs 25 [5%]) and hand—foot syndrome (21 [4%] vs 15 [3%]) were more frequent on continuous than on intermittent treatment. Interpretation: Although this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival, chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer, offering reduced time on chemotherapy, reduced cumulative toxic effects, and improved quality of life. Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break.

Targeted therapies in the treatment of advanced/metastatic NSCLC

The treatment of advanced non-small cell lung cancer (NSCLC) has evolved substantially during the last years. Chemotherapy remains the cornerstone of treatment and prolongs survival with a positive impact on quality of life. However, we seem to have reached a plateau of activity in the treatment of NSCLC. Recently, the addition of bevacizumab or cetuximab to chemotherapy doublets has improved the outcome in selected patients with advanced NSCLC. Furthermore, the use of erlotinib and gefitinib is an alternative for second line treatment. Advances in our understanding of molecular biology of cancer and mechanisms of tumourigenesis have further enabled the discovery of several potential molecular targets and development of novel 'targeted therapies'. The purpose of this study is to review current data on the role of targeted therapies in the treatment of advanced NSCLC. (C) 2009 Elsevier Ltd. All rights reserved.