Objective. Infliximab, an anti-tumor necrosis factor ␣ (anti-TNF␣) antibody, is effective in the treatment of several immunoinflammatory diseases. However, many patients experience primary or secondary response failure, suggesting that individualization of treatment regimens may be beneficial. This study was undertaken to investigate whether serologic monitoring of infliximab bioavailability and immunogenicity in individual patients would be useful in optimizing treatment regimens to improve efficacy and tolerability.Methods. To avoid the use of solid-phase assays, two radioimmunoassays were developed: one for measurement of levels of anti-infliximab antibody, and a functional one for measurement of TNF␣ binding due to infliximab. Sera from 106 randomly selected rheumatoid arthritis patients were tested within 6 months of therapy initiation, and associations between findings of serum assays and disease activity, infusion reactions, and treatment failure occurring within 18 months were assessed.Results. Trough serum infliximab levels after the first 2 intravenous infusions of infliximab at 3 mg/kg varied considerably between patients (range 0-22 g/ ml). At this stage, only 13% of the patients were antiinfliximab antibody positive. With subsequent infusions, the frequency of antibody positivity rose to 30% and 44% (at 3 months and 6 months, respectively), accompanied by diminished trough levels of infliximab. Indeed, low infliximab levels at 1.5 months predicted antibody development and later treatment failure. There were highly significant correlations between high levels of antibodies and later dose increases, side effects, and cessation of therapy. High baseline disease activity, judged by C-reactive protein level and Disease Activity Score, was associated with low levels of infliximab at the early stage of treatment and later development of antiinfliximab antibodies. Cotreatment with methotrexate resulted in slightly reduced antibody levels after 6 months; other disease-modifying antirheumatic drugs and prednisolone had no effect.Conclusion. Development of anti-infliximab antibodies, heralded by low preinfusion serum infliximab levels, is associated with increased risk of infusion reaction and treatment failure. Early monitoring may help optimize dosing regimens for individual patients, diminish side effects, and prevent prolonged use of inadequate infliximab therapy.
Airborne dust in swine and poultry confinements was analyzed to determine concentrations of total and gram-negative bacteria, total fungi, Aspergillus fumigatus and endotoxin. Airborne concentrations of total and gram-negative bacteria in swine and confinement units have been found to be as high as, or higher, than those found in other environments, such as wastewater treatment plants and cotton card rooms, where microbiologically contaminated organic dusts were present. Airborne endotoxin concentrations in the swine units (average 0.12 micrograms/m3) and poultry units (average 0.31 micrograms/m3) were in the range where clinical effects have occurred in other populations. Therefore, health studies of poultry and swine confinement workers with concurrent estimation of the individual daily exposure dose are warranted.
The production learning of vocalizations by manipulation of the sound production organs to alter the physical structure of sound has been demonstrated in only a few mammals. In this natural experiment, we document the vocal behaviour of two juvenile killer whales, Orcinus orca, separated from their natal pods, which are the only cases of dispersal seen during the three decades of observation of their populations. We find mimicry of California sea lion (Zalophus californianus) barks, demonstrating the vocal production learning ability for one of the calves. We also find differences in call usage (compared to the natal pod) that may reflect the absence of a repertoire model from tutors or some unknown effect related to isolation or context.
In the present study, the authors investigated the effects of framing of options on risky decision making in groups of younger adults (M = 23.8 years, n = 192) and older adults (M = 69.1 years, n = 192). The participants were assigned to one of three scenarios varying in the goods at stake (human lives, paintings, money). The authors observed a majority preference in favor of the risky options after negative, but not positive framing. They also found, as they had predicted, that the type of framing effect varied across scenarios, with a bidirectional framing effect for the life-death scenario and unidirectional (risk averse) framing effects when public property (paintings) or personal property (money) were at stake. It is important to note that these choice preference patterns were highly similar across the age groups, which reinforced the conclusion that younger and older adults are equally susceptible to framing effects.
Panton-Valentine leukocidin (PVL)–positive methicillin-resistant
Staphylococcus aureus
(MRSA), sequence type 398 is believed to be of animal origin. We report 2 cases of infection due to PVL–positive MRSA,
spa
type t034, in patients in Sweden who had had no animal contact.
The need to consider sustainability has substantially increased the complexity of implementing construction and infrastructure projects and new management practices have emerged during the past decade to tackle the global sustainability challenges, where the engagement and coordination of broader competences from stakeholders throughout the supply chain is required. This new project management paradigm has been accompanied by greater attention to the concept of collaborative business arrangements, often called partnering, that has emerged in construction and infrastructure projects to improve project deliveries. However, there are uncertainties about the optimal strategy to foster, integrate and maintain the required collaboration, particularly in sustainable management practices in infrastructure maintenance projects. This paper addresses these uncertainties, based on a single case study of an infrastructure maintenance contract involving an extensive collaborative business arrangement. The findings reveal that different collaborative practices affect diverse aspects of sustainable project management. Further, the extensive collaborative business arrangement has promoted sustainable deliveries based upon organizational learning and continuous improvements. Thus, this study offers an encouraging example of how extensive collaboration can be fostered and play a key role in sustainable project management practices.
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