Связи изменений среднемесячных ОСО над Антарктикой и площади теплого тропического бассейна Тихого океана при современном потеплении климата

Объектом данного исследования выбраны изменения распределения среднемесячных значений ОСО над Антарктикой, а также площади ТТБ в западном полушарии. Предметом исследования есть изменения статистических связей между указанными процессами, происходившими за период современного потепления климата. Целью работы есть выявление их связей, которые на протяжении периода современного потепления климата усиливались устойчиво и ныне являются значимыми

Using discrete choice experiments to investigate subject preferences for preventive asthma medication

Background and objective: Long-term adherence to inhaled corticosteroids is poor despite the crucial role of preventer medications in achieving good asthma outcomes. This study was undertaken to explore patient preferences in relation to their current inhaled corticosteroid medication, a hypothetical preventer or no medication. Methods: A discrete choice experiment was conducted in 57 adults with mild-moderate asthma and airway hyper-responsiveness, who were using inhaled corticosteroid ≤500 μg/day (beclomethasone equivalent). In the discrete choice experiment, subjects evaluated 16 hypothetical scenarios made up of 10 attributes that described the process and outcomes of taking asthma medication, with two to four levels for each attribute. For each scenario, subjects chose between the hypothetical medication, the medication they were currently taking and no asthma medication. A random parameter multinomial logit model was estimated to quantify subject preferences for the aspects of taking asthma medication and the influence of attributes on medication decisions. Results: Subjects consistently made choices in favour of being able to do strenuous and sporting activities with or without reliever, experiencing no side-effects and never having to monitor their peak flow. Frequency of collecting prescriptions, frequency of taking the medication, its route of administration and the strength of the doctor recommendation about the medication were not significant determinants of choice. Conclusions: The results of this study suggest that patients prefer a preventer that confers capacity to maximize physical activity, has no side-effects and does not require daily peak flow monitoring. © 2007 The Authors

Trajectories of adolescent life satisfaction

Increasing global policy interest in measuring and improving population wellbeing has prompted academic investigations into the dynamics of lifespan life satisfaction. Yet little research has assessed the complete adolescent age range, although it harbours developmental changes that could affect wellbeing far into adulthood. This study investigates how life satisfaction develops throughout the whole of adolescence, and compares this development to that in adulthood, by applying exploratory and confirmatory latent growth curve modelling to UK and German data, respectively (37 076 participants, 10–24 years). We find a near universal decrease in life satisfaction during adolescence. This decrease is steeper than at any other point across adulthood. Further, our findings suggest that adolescent girls' life satisfaction is lower than boys’, but that this difference does not extend into adulthood. The study highlights the importance of studying adolescent subjective wellbeing trajectories to inform research, policy and practice

Comparison of monoclonal antibodies 17-1A and 323/A3: the influence of the affinity on tumour uptake and efficacy of radioimmunotherapy in human ovarian cancer xenografts.

The low-affinity monoclonal antibody (MAb) chimeric 17-1A(c-17-1A) and the high-affinity MAb mouse 323/A3 (m-323/A3) were used to study the effect of the MAb affinity on the tumour uptake and efficacy of radioimmunotherapy in nude mice bearing subcutaneously the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. Both MAbs are directed against the same pancarcinoma glycoprotein. In vitro, the number of binding sites on tumour cells at 4 degrees C was similar for both MAbs, but m-323/A3 had an approximately 5-fold higher affinity (1.3-3.0x10(9) M-1) than c-17-1A (3.0-5.4x10(8) M-1). This difference in affinity was more extreme at 37 degrees C, when no binding of c-17-1A could be observed. MAb m-323/A3 completely blocked binding of c-17-1A to tumour cells, whereas the reverse was not observed. Immunohistochemistry showed a similar but more intense staining pattern of m-323/A3 in human ovarian cancer xenografts than of c-17-1A. In vivo, the blood clearance in non-tumour-bearing nude mice was similar for both MAbs with terminal half-lives of 71.4 h for m-323/A3 and 62.7 h for c-17-1A. MAb m-323/A3 targeted better to tumour tissue, but was more heterogeneously distributed than c-17-1A. The cumulative absorbed radiation dose delivered by m-323/A3 to tumour tissue was 2.5- to 4.7-fold higher than that delivered by c-17-1A. When mice were treated with equivalent radiation doses of 131(I)m-323/A3 and 131(I)c-17-1A, based on a correction for the immunoreactivity of the radiolabelled MAbs, m-323/A3 induced a better growth inhibition in two of the three xenografts. When the radiation doses were adjusted to obtain a similar amount of radiation in the tumour c-17-1A was more effective in tumour growth inhibition in all three xenografts

Biologics registers in RA: methodological aspects, current role and future applications

The beginning of the 21st century saw a biopharmaceutical revolution in the treatment of inflammatory rheumatic diseases, particularly rheumatoid arthritis. The fast-evolving use of biologic therapies highlighted the need to develop registers at national and international levels with the aim of collecting long-term data on patient outcomes. Over the past 15 years, many biologics registers have contributed a wealth of data and provided robust and reliable evidence on the use, effectiveness and safety of these therapies. The unavoidable challenges posed by the continuous introduction of new therapies, particularly with regard to understanding their long-term safety, highlights the importance of learning from experience with established biologic therapies. In this Perspectives article, the role of biologics registers in bridging the evidence gap between efficacy in clinical trials and real-world effectiveness is discussed, with a focus on methodological aspects of registers, their unique features and challenges and their role going forward

Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis

Change from baseline in swollen (a) and tender (b) joint counts. *Error bars show upper SE for placebo and lower SE for namilumab. SE standard error, SJC swollen joint count, TJC tender joint count. (PDF 1292 kb

Challenges and Solutions to the Measurement of Neurocognitive Mechanisms in Developmental Settings

Identifying early neurocognitive mechanisms that confer risk for mental health problems is one important avenue as we seek to develop successful early interventions. Currently, however, we have limited understanding of the neurocognitive mechanisms involved in shaping mental health trajectories from childhood through young adulthood, and this constrains our ability to develop effective clinical interventions. In particular, there is an urgent need to develop more sensitive, reliable, and scalable measures of individual differences for use in developmental settings. In this review, we outline methodological shortcomings that explain why widely used task-based measures of neurocognition currently tell us little about mental health risk. We discuss specific challenges that arise when studying neurocognitive mechanisms in developmental settings, and we share suggestions for overcoming them. We also propose a novel experimental approach—which we refer to as “cognitive microscopy”—that involves adaptive design optimization, temporally sensitive task administration, and multilevel modeling. This approach addresses some of the methodological shortcomings outlined above and provides measures of stability, variability, and developmental change in neurocognitive mechanisms within a multivariate framework

Multiple determinants of lifespan memory differences

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss

Preserved cognitive functions with age are determined by domain-dependent shifts in network responsivity

Healthy ageing has disparate effects on different cognitive domains. The neural basis of these differences, however, is largely unknown. We investigated this question by using Independent Components Analysis to obtain functional brain components from 98 healthy participants aged 23-87 years from the population-based Cam-CAN cohort. Participants performed two cognitive tasks that show age-related decrease (fluid intelligence and object naming) and a syntactic comprehension task that shows age-related preservation. We report that activation of task-positive neural components predicts inter-individual differences in performance in each task across the adult lifespan. Furthermore, only the two tasks that show performance declines with age show age-related decreases in task-positive activation of neural components and decreasing default mode (DM) suppression. Our results suggest that distributed, multi-component brain responsivity supports cognition across the adult lifespan, and the maintenance of this, along with maintained DM deactivation, characterizes successful ageing and may explain differential ageing trajectories across cognitive domains