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Nested data arise frequently in clinical research. The nesting might be hierarchical, such as patients nested within clinicians, or it might be longitudinal, such as repeated assessments over time nested within individuals. As articulated in this chapter, whenever and however nesting occurs, it is necessary to account for the statistical dependence of observations within units when analyzing the data. Further, it is important to determine the level(s) of the data at which predictors exert their effects. Multilevel models are a particularly popular and useful approach for addressing these issues. We thus describe these models in detail, illustrating the application of multilevel models in clinical research via two examples. The first example considers nesting of siblings within families and demonstrates the importance of separating within- versus between-family effects. The second example focuses on the application of multilevel models with repeated measures to evaluate within-person change over time. Additionally, we provide a brief survey of other approaches to the analysis of nested data (e.g., cluster-robust standard errors, generalized estimating equations, fixed-effects models).
This article discusses prospects and challenges related to the use of meta-regression models (MRMs) for ecosystem service benefit transfer, with an emphasis on validity criteria and post-estimation procedures given sparse attention in the ecosystem services literature. We illustrate these topics using a meta-analysis of willingness to pay for water quality changes that support aquatic ecosystem services and the application of this model to estimate water quality benefits under alternative riparian buffer restoration scenarios in New Hampshire's Great Bay Watershed. These illustrations highlight the advantages of MRM benefit transfers, together with the challenges and data needs encountered when quantifying ecosystem service values.
Electroconvulsive therapy (ECT) is a fast-acting intervention for major depressive disorder. Previous studies indicated neurotrophic effects following ECT that might contribute to changes in white matter brain structure. We investigated the influence of ECT in a non-randomized prospective study focusing on white matter changes over time.
Twenty-nine severely depressed patients receiving ECT in addition to inpatient treatment, 69 severely depressed patients with inpatient treatment (NON-ECT) and 52 healthy controls (HC) took part in a non-randomized prospective study. Participants were scanned twice, approximately 6 weeks apart, using diffusion tensor imaging, applying tract-based spatial statistics. Additional correlational analyses were conducted in the ECT subsample to investigate the effects of seizure duration and therapeutic response.
Mean diffusivity (MD) increased after ECT in the right hemisphere, which was an ECT-group-specific effect. Seizure duration was associated with decreased fractional anisotropy (FA) following ECT. Longitudinal changes in ECT were not associated with therapy response. However, within the ECT group only, baseline FA was positively and MD negatively associated with post-ECT symptomatology.
Our data suggest that ECT changes white matter integrity, possibly reflecting increased permeability of the blood–brain barrier, resulting in disturbed communication of fibers. Further, baseline diffusion metrics were associated with therapy response. Coherent fiber structure could be a prerequisite for a generalized seizure and inhibitory brain signaling necessary to successfully inhibit increased seizure activity.
Poor physiological self-regulation has been proposed as a potential biological vulnerability for adolescent suicidality. This study tested this hypothesis by examining the effect of parasympathetic stress responses on future suicide ideation. In addition, drawing from multilevel developmental psychopathology theories, the interplay between parasympathetic regulation and friendship support, conceptualized as an external source of regulation, was examined. At baseline, 132 adolescent females (M age = 14.59, SD = 1.39) with a history of mental health concerns participated in an in vivo interpersonal stressor (a laboratory speech task) and completed self-report measures of depressive symptoms and perceived support within a close same-age female friendship. Respiratory sinus arrhythmia (RSA) was measured before and during the speech task. Suicide ideation was assessed at baseline and at 3, 6, and 9 months follow-up. The results revealed that females with greater relative RSA decreases to the laboratory stressor were at higher risk for reporting suicide ideation over the subsequent 9 months. Moreover, parasympathetic responses moderated the effect of friendship support on suicide ideation; among females with mild changes or higher relative increases in RSA, but not more pronounced RSA decreases, friendship support reduced risk for future suicide ideation. Findings highlight the crucial role of physiological and external regulation sources as protective factors for youth suicidality.
Multivariate statistical analysis (MSA) is applied to the extraction of chemically relevant signals acquired with a micro-X-ray fluorescence (μ-XRF) mapping (full-spectral imaging) system. The separation of components into individual histograms enables separation of overlapping peaks, which is useful in qualitatively determining the presence of chemical species that have overlapping emission lines, and holds potential for quantitative analysis of constituent phases via these same histograms. The usefulness of MSA for μ-XRF analysis is demonstrated by application to a geological rock core obtained from a subsurface compressed air energy storage (CAES) site. Coupling of the μ-XRF results to those of quantitative powder X-ray diffraction analysis enables improved detection of trace phases present in the geological specimen. The MSA indicates that the spatial distribution of pyrite, a potentially reactive phase by oxidation, has low concentration and thus minimal impact on CAES operations.
The person-oriented approach seeks to match theories and methods that portray development as a holistic, highly interactional, and individualized process. Over the past decade, this approach has gained popularity in developmental psychopathology research, particularly as model-based varieties of person-oriented methods have emerged. Although these methods allow some principles of person-oriented theory to be tested, little attention has been paid to the fact that these methods cannot test other principles, and may actually be inconsistent with certain principles. Lacking clarification regarding which aspects of person-oriented theory are testable under which person-oriented methods, assumptions of the methods have sometimes been presented as testable hypotheses or interpreted as affirming the theory. This general blurring of the line between person-oriented theory and method has even led to the occasional perception that the method is the theory and vice versa. We review assumptions, strengths, and limitations of model-based person-oriented methods, clarifying which theoretical principles they can test and the compromises and trade-offs required to do so.
That behavior reflects ongoing transactions between person and
context is an enshrined proposition of developmental theory, although
the dynamic properties of these transactions have not been fully
appreciated. In this article, we focus on reciprocal links between the
Pearlin mastery scale and life events in the transition to adulthood, a
strategic relationship given that control orientations are thought to
mediate links between stressors and a range of indicators of distress,
and given that life events become increasingly likely in young
adulthood. Drawing on 12 waves of data from the Youth Development
Study, spanning ages 14–15 to 26–27, we examine a series of
growth curve models that interrelate mastery and life events. Results
for females reveal that mastery during the senior year of high school
predicts life events for the following 4-year period, which in turn
predicts mastery over the 5-year period spanning ages 21–22 to
26–27. For males, mastery during the senior year (and perhaps the
sophomore year) predicts subsequent life events, which in turn have
short-term implications for mastery. Thus, transactions between life
events and mastery are observed, although the temporal patterns of
these exchanges are complex. These findings are discussed in terms of
the developmental properties of transactions between person and
context.The Youth Development Study is
supported by grants from the National Institute of Child Health and
Human Development (HD44138) and the National Institute of Mental Health
(MH42843). Support for the research reported in this article comes in
part from a subcontract to the first author (“Role configurations
and well-being in the transition to adulthood”). The authors
thank Lance Erickson and Sondra Smolek for helpful
This paper examines individual differences in the rate of early lexical development with a specific interest in gender differences. Twenty-six children were assessed monthly from either 8, 9, or 10 months of age through 14 months of age, using the MacArthur Communicative Development Inventory: Words and Gestures. Individual differences in developmental trajectories of vocabulary comprehension and production were explored using two analytic approaches. The first involved traditional parametric statistics, while the latter utilized classification procedures. Both techniques demonstrated that the lexical development of girls outpaced that of boys. The inductive approach also revealed the presence of distinctive “fast” and “slow” trajectories for both comprehension and production that were not exclusively segregated by gender. Cases exhibiting fast trajectories were predominantly girls, but several boys also followed this developmental pattern. The opposite pattern emerged for the slow trajectories. There was strong correspondence between production and comprehension, but a few cases clustered into the fast development group on one measure and the slow group on the other. The identification of these outliers may offer an important tool for exploring mechanisms of language development. Validation of the clustering results was based on the prospective prediction of an external criterion variable, namely, lexical development at 21 months, and by replication on an independent sample.
This paper outlines investigations into a potentially revolutionary approach to tissue engineering. Tissue is a complex three-dimensional structure that contains many different biomaterials such as cells, proteins, and extracellular matrix molecules that are ordered in a very precise way to serve specific functions. In order to replicate such complex structure, it is necessary to have a tool that could deposit all these materials in an accurate and controlled fashion. Most methods to fabricate living three-dimensional structures involve techniques to engineer biocompatible and biodegradable scaffolding, which is then seeded with living cells to form tissue. This scaffolding gives the tissue needed support, but the resulting tissue inherently has no microscopic cellular structure because cells are injected into the scaffolding where they adhere at random. We have developed a novel technique that actually engineers tissue, not scaffolding, that includes the mesoscopic cellular structure inherent in natural tissues. This approach uses a laser-based rapid prototyping system known as matrix assisted pulsed laser evaporation direct write (MAPLE DW) to construct living tissue cell-by-cell. This manuscript details our efforts to rapidly and reproducibly fabricate complex 2D and 3D tissue structures with MAPLE-DW by placing different cells and biomaterials accurately and adherently on the mesoscopic scale
The structural properties of Si/SiGe quantum wires, which were grown by local solid source molecular beam epitaxy through a Si3N4/SiO2 wire-like shadow mask, were investigated by means of high resolution x-ray coplanar and x-ray grazing incidence diffraction, as well as by transmission electron microscopy. High resolution x-ray coplanar diffraction was used to obtain the average in-plane strain in Si/SiGe wires before and after removing the Si3N4/SiO2 shadow mask. x-ray grazing incidence diffraction measurements were performed to obtain information on the shape of the wires and on the depth-dependent strain relaxation. A finite element method was used to calculate the strain distribution in the Si/SiGe wires and in the Si substrate which clearly show the influence of the Si3N4/SiO2 shadow masks on the strain status of the Si/SiGe wires in agreement with the experimental data.