A MYC-rearrangement is a negative prognostic factor in stage II, but not in stage I diffuse large B-cell lymphoma.

MYC oncogene rearrangements (MYC-R) negatively affect survival in patients with Ann Arbor stage III-IV diffuse large B-cell lymphoma (DLBCL), but their impact in limited stage (LS) I-II is unclear. Therefore, we assessed the impact of MYC-R on progression-free survival (PFS) and overall survival (OS) in LS DLBCL patients at the population level. We identified 1,434 LS DLBCL patients with known MYC-R status diagnosed between 2014 and 2020, who received R-CHOP(-like) regimens using the Netherlands Cancer Registry, with survival follow-up until February 2022. Stage I patients with (n = 83, 11%) and without (n = 650, 89%) a MYC-R had similar 2-years PFS (89% and 93%, p = 0.63) and OS (both 95%, p = 0.22). Conversely, stage II DLBCL patients with a MYC-R (n = 90, 13%) had inferior survival outcomes compared to stage II patients without a MYC-R (n = 611, 87%) (PFS 70% vs. 89%, p = 0.001; OS 79% vs. 94%, p < 0.0001). Both single MYC-R (single hit, n = 36) and concurrent BCL2 and/or BCL6 rearrangements (double/triple hit, n = 39) were associated with increased mortality and relapse risk. In conclusion, in stage II DLBCL a MYC-R is negatively associated with survival. In stage I DLBCL, however, survival outcomes are excellent irrespective of MYC-R status. This challenges the diagnostic assessment of MYC-R in stage I DLBCL patients.

Effect of NaCl and sucrose tastants on protein composition of oral fluid analysed by SELDI-TOF-MS.

During eating, human saliva is secreted into the oral cavity by salivary glands. The relative contribution of different glands to total salivary flow rate depends, among other factors, on the tastants in the food. Few reports indicated that also the salivary protein composition depends on the tastant make-up of the food. We studied the influence of sodium-chloride- and sucrose solutions on the presence of proteins in the M(r) range 2-20kDa in whole saliva. Upon oral stimulation with a sodium chloride solution, a sucrose solution or water, we collected whole saliva from 14 volunteers after t=1 min, t=11 min and t=20 min. Saliva protein profiles were analysed by SELDI-TOF-MS. SELDI-TOF-MS intensities of m/z values representing different protein masses were compared between subjects, tastants and time conditions. For subsets of the 33 detected masses, significant effects were observed for all factors, with most masses involved in the Subjects effect: m/z(Subjects)>m/z(Time×Stimulus)>m/z(Stimulus)>m/z(Time). Most effects on saliva protein composition were observed at t=1 min, whilst almost no effects were observed at t=11 min and t=20 min. When considering the Stimulus×Time interaction, we identified four different stimulus-response patterns. Proteins identified in the present study, and attributed to specific glands or tissues in literature, were used to associate stimulus-response patterns with tissue provenances. Observed stimulus-response patterns were not uniquely associated to particular glands and tissues. Hence, there was no evidence of the involvement of particular tissues or glands in tastant-specific protein responses. In conclusion, oral stimulation with different tastants affects salivary protein composition in a protein- and stimuli dependent way, which seems not be associated with any specific tissues or glands of origin.

Payment, compensation and replacement--the ethics and motivation of blood and plasma donation.

The supply of blood and plasma to produce haemotherapies varies around the world, but all environments need donors to furnish the raw material. Many countries still lack adequate supply, and the question of what amounts of blood and plasma are required for optimal treatment is still unresolved. The issue of compensating donors has been a controversial and emotive one in blood transfusion for many decades. Donors are conventionally classified as paid, voluntary or replacement, and a level of stigma, based on safety and ethical considerations, has been attached to paid donation. This review points to evidence which renders many of these concerns redundant. Purist arguments against compensated donation have little basis in evidence and would lead to many of today's voluntary donors being designated as paid, because of the large range of incentives used to recruit and retain them. Misplaced application of 'Titmussian' volunteerism has precipitated its own safety and supply problems. Current systems of compensation and replacement are needed to maintain supplies of essential products and lead to safe products in controlled environments. We propose that a plurality of routes towards donation is an appropriate paradigm in the heterogeneous landscape of blood and plasma product supply.

Passivation oxide controlled selective carbon nanotube growth on metal substrates.

Vertically aligned arrays of multi-wall carbon nanotubes (MWNT) are grown on Inconel 600, a nickel-based super-alloy. Using x-ray photoelectron spectroscopy (XPS) and chemical vapor deposition (CVD) growth of the MWNTs it is shown that a stable oxidation barrier is required for the stabilization of iron on the substrate and subsequent nanotube growth. This evidence for passivation oxide supported growth of MWNTs was then used to grow MWNTs on patterned oxidized substrates in a selective growth furnace. The unique advantage of this patterned growth on Inconel 600 is found to be the chromia passivation layer's electrical conductivity (measured value of 1.08 micro Omega m), creating the opportunity for low resistivity electrodes made from nanotubes. Inconel substrates with 100 microm long aligned MWNTs are demonstrated to exhibit an average resistance value of 2 Omega.

Continuous analysis of parotid saliva during resting and short-duration simulated chewing.

OBJECTIVE: Parotid saliva flow is increased by mastication and its composition is also modified. The aim of this work was to clarify the relationships between flow rate, pH and protein concentration, during resting and short-duration simulated chewing, using continuous and fractional saliva collections. DESIGN: Parotid saliva flow rate, pH and protein concentration, as it exits the Stensen's duct, were determined on seven subjects in response to one and 30 ipsilateral jaw clenches. To achieve this, we have developed a system able to collect parotid saliva and to measure continuously flow rate, pH and protein concentration and synchronised to the values at the exit of the duct. RESULTS: With increase in flow rate, pH increased linearly and its protein concentration decreased linearly with the logarithm of the flow rate. With an increase in flow rate from 50 to 500 microl/min, the pH increased from 5.8 to 7.0 and the protein concentration decreased from 1.0 to 0.7 g/l. Measurements made on parotid saliva fractions confirmed the variations in pH and protein concentration with flow rate and showed that alpha-amylase concentration was significantly related to both salivary conductivity and protein concentration. CONCLUSIONS: Continuous measurements of salivary flow and composition offer a simple and convenient way to determine the precise relationships between different types of oral stimulation and parotid salivary flow and composition.

Perspectives on compensated plasma donation.

The subject of compensating donors has been and sometimes still is a topic for lively discussion. It is my view that compensating plasma donors for their time and effort is appropriate when done in a well regulated environment. I will attempt in this presentation to outline the reasons why this is the case.

Improving inpatient antibiotic prescribing: insights from participation in a national collaborative.

BACKGROUND: Increasing rates of antimicrobial resistance and the role antibiotic overuse plays in contributing to this problem have been widely documented and have prompted appeals to change prescribing practices. How to actually achieve such changes represents a major challenge. As part of the Institute for Healthcare Improvement (IHI) Breakthrough Series project Improving Prescribing Practices (IPP), in 1997-1998, Cook County Hospital (Chicago) worked with other institutions that chose antibiotics as their focus in this national collaborative. PRACTICAL SUGGESTIONS: Practical suggestions are offered within six categories--adopting a general approach to improving antibiotic prescribing (marshalling credible evidence, addressing physician concerns and skepticism, and removing barriers to make it easier for prescribers to change); rethinking guidelines (providing syndrome-based guidance, revising national guidelines for local use, defining scenarios in which drug(s) can be safely withheld, offering alternatives, prospectively resolving conflicts over drug of choice and empiric regimens, and defining situations in which immediate treatment is and is not critical); getting the message out and changes implemented (using antibiotic order forms, computer order entry, and infectious disease specialist consultation); building viable linkages to leverage change (bridging disciplines); improving measurement; and promoting nondrug strategies and patients' roles in treating and preventing infection. CONCLUSION: Antimicrobials are unique, being the only class of drug therapy that affects not only the patient to whom it is prescribed but other current and future patients as well. Institutions therefore have a special responsibility to ensure their efficient and judicious use. It is often easier to prescribe antibiotics than to exercise restraint.

The influence of olfactory concept on the probability of detecting sub- and peri-threshold components in a mixture of odorants.

The headspace of apple juice was analysed to obtain an ecologically relevant stimulus model mixture of apple volatiles. Two sets of volatiles were made up: a set of eight supra-threshold volatiles (MIX) and a set of three sub-threshold volatiles. These sets were used to test the hypothesis that sub-threshold components can change the quality of a familiar smelling mixture of odorants when added to this mixture. In order to test this hypothesis, three successive dilutions of the sub-threshold volatiles were prepared in such a way that the strongest was at the threshold concentration and the two lower concentrations were below the threshold. The detection probabilities of the sub-threshold components in a blank stimulus were compared with the detectabilities in MIX. The sub- and peri-threshold volatiles were detected no better in MIX than in a blank. On the contrary, sub- and peri-threshold volatiles were better detected alone than when added to MIX. However, when the group of subjects was split into two sub-groups, employing either a rough or a detailed concept definition of the target stimulus, respectively, the subjects with highly refined concepts were better able to detect the presence of sub-threshold volatiles in MIX than those with poorly refined stimulus concepts. The effect of stimulus concept definition occurred independently of the proportions of correct detections of sub-threshold volatiles in a blank.

Uncertainty in decision models analyzing cost-effectiveness: the joint distribution of incremental costs and effectiveness evaluated with a nonparametric bootstrap method.

PURPOSE: To illustrate the use of a nonparametric bootstrap method in the evaluation of uncertainty in decision models analyzing cost-effectiveness. METHODS: The authors reevaluated a previously published cost-effectiveness analysis that used a Markov model comparing initial percutaneous transluminal angioplasty with bypass surgery for femoropopliteal lesions. Each probability in the model was simulated with a first-order Monte Carlo simulation to represent sampling uncertainty. Superimposed on this, a second-order Monte Carlo simulation was performed to represent parameter uncertainty, drawing the probability values from nonparametric distributions based on published data or from primary collected data as available. After simulation of a mixed (i.e., non-identical) cohort of 30,000 patients, 3,000 bootstrap samples of 1,000 patients each were drawn and the joint distribution of mean incremental costs and mean effectiveness gained was evaluated. RESULTS: Using a bootstrap sample size of 1,000 patients, 92.7% of the joint distribution of mean incremental costs and mean effectiveness gained fell in the quadrant where angioplasty dominated bypass surgery. Another 6.9% of samples demonstrated either greater effectiveness with an incremental cost-effectiveness ratio of at most $20,000/QALY gained, or cost savings with a ratio of at least $20,000 saved/QALY lost. CONCLUSION: A nonparametric bootstrap method can be used to estimate the joint distribution of mean incremental costs and mean effectiveness gained, and the results can provide an understanding of the uncertainty in a cost-effectiveness analysis based on a decision model.

Heterogeneity in the relationship between the time tradeoff and Short Form-36 for HIV-infected and primary care patients.

OBJECTIVES: Evidence in the literature suggests that the overall correlation between descriptive and valuational measures of health are weak to moderate. In this study, the relationship between descriptive health status measures, obtained using the Short-Form 36, and health values, measured with the time tradeoff, was explored. METHODS: Two groups of patients matched for age and gender were interviewed. One group comprised 139 human immunodeficiency virus (HIV)-infected patients; the other group comprised 124 primary care patients. The relationship between the SF-36 and the time tradeoff was estimated, assuming homogeneity across patients, using multiple regression analysis. Subsequently, the relationship was examined assuming heterogeneity across patients and using the expectation maximization algorithm in a maximum likelihood context (latent class analysis). RESULTS: Four classes, representing 47%, 13%, 8%, and 32% of the population, respectively, were found. The overall percentage of variation explained under the assumption of a homogeneous relationship was only 33% as compared with 85% when heterogeneity was accounted for. Only three characteristics (educational level, employment status, and the SF-36 social functioning score) sufficed to generate a nearly perfect classification of the patients. CONCLUSIONS: Heterogeneity across subjects should be taken into account in describing the relationship between health values and health status dimensions.

Heterogeneity in the relationship between the standard-gamble utility measure and health-status dimensions.

The authors assessed the relationship between the standard-gamble utility measure and the RAND-36 health-status dimensions, taking into account possible heterogeneity among patients in the weights they assign to different health-status dimensions. A questionnaire including both measures was completed by 68 patients with symptomatic peripheral arterial disease. Conventional multiple regression analysis, assuming a homogeneous relationship for the total population between the standard-gamble utility and the RAND-36 health-status dimensions, demonstrated that only the dimension social functioning was significant (p < 0.05), which accounted for 10% of the variation. Assuming that the population consisted of two separate classes demonstrated superior representation of the data. Latent class analysis was used to estimate the unknown parameters and class memberships. In the first class, consisting of 65% of the patients, the relationship between the standard-gamble utility and the dimension general health perception was significant. The within-R2 was 12%. The second class represented 35% of the patients and showed significant coefficients for the dimensions social functioning and role limitations due to physical problems, which accounted for 80% of the variation. The overall percentage of variation explained by latent class analysis was 49%. The results suggest that patients with symptomatic peripheral arterial disease belong to a variety of classes, all with class-specific relationships between the standard-gamble utility and the RAND-36 health-status dimensions.