The Effect of Air Knife Geometry on Coated Board Properties

The purpose of this thesis was to determine the effect of air knife angle and the distance between the air knife blades and backing-roll on coated board properties. Results of the experiment indicated that increasing the angle resulted in more uniform and smaller coated pore size. Increasing the distance resulted in more uniform pores with no effect on size. The optimum angle of operation was found to be between 17 and 20 degrees (approximate impingement angle) and optimum distance was determined to be between 80 and 90 mils. Further work that can be completed as a result of this thesis include; jet patterns of air knife isobars, locating exact optimization of angle and distance, determination of exact air jet angle, and the effect of orifice opening

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

Conching chocolate:A prototypical transition from frictionally jammed solid to flowable suspension with maximal solid content

The mixing of a powder of 10-50{\mu}m primary particles into a liquid to form a dispersion with the highest possible solid content is a common industrial operation. Building on recent advances in the rheology of such 'granular dispersions', we study a paradigmatic example of such powder incorporation: the conching of chocolate, in which a homogeneous, flowing suspension is prepared from an inhomogeneous mixture of particulates, triglyceride oil and dispersants. Studying the rheology of a simplified formulation, we find that the input of mechanical energy and staged addition of surfactants combine to effect a considerable shift in the jamming volume fraction of the system, thus increasing the maximum flowable solid content. We discuss the possible microscopic origins of this shift, and suggest that chocolate conching exemplifies a ubiquitous class of powder-liquid mixing

Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand

The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

Purpose: People living with cancer and haematological malignancies are at increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. Methods: This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. Results: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction (PCR) coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5% respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Lymphoma patients had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01 respectively. p<0.001 for both). Conclusions: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous, and lower than the general population. Many patients with cancer will remain at increased risk of coronavirus infections, even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic

VICTOR : a phase III placebo-controlled trial of rofecoxib in colorectal cancer patients following surgical resection

Background: The cyclo-oxygenase-2 inhibitor, rofecoxib (R) was hypothesised to improve survival in cancer patients who had undergone surgery for colorectal cancer (CRC). This trial recruited from April 2002 until September 2004 when R was withdrawn over concerns about its cardiovascular safety (CVS). This report provides preliminary efficacy results. Methods: Recruited patients had undergone Ro resection of a stage II/III CRC and completion of adjuvant therapy (radiotherapy/chemotherapy/both/neither) less than 12 weeks previously. Excluded patients were those with active peptic ulceration, gastro-intestinal bleeding and those receiving long-term NSAID therapy (except low dose aspirin). 7,000 patients were planned to receive 25mg R daily or an identical placebo (P) for 2 or 5 years, with the goal of detecting a reduction in risk of death - hazard ratio (HR) 0.82. After the trial's premature closure, a modified protocol of the post- treatment follow-up phase and revised statistical analysis plan permitted the detection of a reduction (HR=0.75) in risk of death with 87% power, type I error 0.05, with one pre-planned event-driven interim analysis. Overall survival (OS) and disease-free survival (DFS) were both measured from randomisation, with DFS defined as the time to recurrence or death from any cause. Results: 1,167 of 1,217 patients randomised to R and 1,160 0f 1,217 randomised to P received treatment with median durations of 7.4 months and 8.2 months respectively. Median follow-up was 3.0 and 3.1 years in the two arms (R vs P), with 177 vs 191 deaths and 291 vs 316 DFS events. This pre-planned Kaplan-Meier and log- rank analysis demonstrated that the R patients had slightly longer OS than the P patients, HR 0.94 (95% CI 0.77-1.16; p=0.57). Similarly DFS was slightly higher in the R patients, HR 0.91 (95% CI 0.78-1.07; p=0.25). 19 patients in each arm died without recurrence of CRC. Conclusions: In this study of short treatment duration treatment with R is unlikely to result in a substantial improvement in OS but a small protective effect against recurrence is suggested

VICTOR : a phase III placebo-controlled trial of rofecoxib in colorectal cancer patients following surgical resection

Background: The cyclo-oxygenase-2 inhibitor, rofecoxib (R) was hypothesised to improve survival in cancer patients who had undergone surgery for colorectal cancer (CRC). This trial recruited from April 2002 until September 2004 when R was withdrawn over concerns about its cardiovascular safety (CVS). This report provides preliminary efficacy results. Methods: Recruited patients had undergone Ro resection of a stage II/III CRC and completion of adjuvant therapy (radiotherapy/chemotherapy/both/neither) less than 12 weeks previously. Excluded patients were those with active peptic ulceration, gastro-intestinal bleeding and those receiving long-term NSAID therapy (except low dose aspirin). 7,000 patients were planned to receive 25mg R daily or an identical placebo (P) for 2 or 5 years, with the goal of detecting a reduction in risk of death - hazard ratio (HR) 0.82. After the trial's premature closure, a modified protocol of the post- treatment follow-up phase and revised statistical analysis plan permitted the detection of a reduction (HR=0.75) in risk of death with 87% power, type I error 0.05, with one pre-planned event-driven interim analysis. Overall survival (OS) and disease-free survival (DFS) were both measured from randomisation, with DFS defined as the time to recurrence or death from any cause. Results: 1,167 of 1,217 patients randomised to R and 1,160 0f 1,217 randomised to P received treatment with median durations of 7.4 months and 8.2 months respectively. Median follow-up was 3.0 and 3.1 years in the two arms (R vs P), with 177 vs 191 deaths and 291 vs 316 DFS events. This pre-planned Kaplan-Meier and log- rank analysis demonstrated that the R patients had slightly longer OS than the P patients, HR 0.94 (95% CI 0.77-1.16; p=0.57). Similarly DFS was slightly higher in the R patients, HR 0.91 (95% CI 0.78-1.07; p=0.25). 19 patients in each arm died without recurrence of CRC. Conclusions: In this study of short treatment duration treatment with R is unlikely to result in a substantial improvement in OS but a small protective effect against recurrence is suggested

Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial

Purpose Laboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 ( COX-2) pathway in colorectal carcinogenesis. The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC). Patients and Methods Patients who had undergone potentially curative surgery and completion of adjuvant therapy for stage II and III CRC were randomly assigned to receive rofecoxib (20 mg daily) or placebo. The primary end point was overall survival (OS). Where formalin-fixed paraffin-embedded tumor tissue samples were available, COX-2 expression was evaluated by immunohistochemistry and correlated with clinical outcome. Results Two thousand four hundred thirty-four patients were entered onto the study. The trial was terminated early because of the worldwide withdrawal of rofecoxib. At this point, 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment durations of 7.4 and 8.2 months, respectively. For the rofecoxib and placebo arms, median follow-up times were 4.84 and 4.85 years, with 241 and 246 deaths and 297 and 329 recurrences, respectively. No difference was demonstrated in OS (hazard ratio [HR] = 0.97; 95% CI, 0.81 to 1.16; P = .75) or recurrence (HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) comparing the two groups. Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients, but neither prognostic nor predictive effects were observed. Conclusion In this study of abbreviated therapy in the adjuvant setting of CRC, rofecoxib did not improve OS or protect from recurrence in unselected patients. In addition, COX-2 expression did not correlate with prognosis overall or predict effectiveness of COX-2 inhibitors