The micromechanics of the superficial zone of articular cartilage.

Journal ArticleOBJECTIVE: To investigate the relationships between the unique mechanical and structural properties of the superficial zone of articular cartilage on the microscopic scale. DESIGN: Fresh unstained equine metacarpophalangeal cartilage samples were mounted on tensile and compressive loading rigs on the stage of a multiphoton microscope. Sequential image stacks were acquired under incremental loads together with simultaneous measurements of the applied stress and strain. Second harmonic generation was used to visualise the collagen fibre network, while two photon fluorescence was used to visualise elastin fibres and cells. The changes visualised by each modality were tracked between successive loads. RESULTS: The deformation of the cartilage matrix was heterogeneous on the microscopic length scale. This was evident from local strain maps, which showed shearing between different regions of collagen under tensile strain, corrugations in the articular surface at higher tensile strains and a non-uniform distribution of compressive strain in the axial direction. Chondrocytes elongated and rotated under tensile strain and were compressed in the axial direction under compressive load. The magnitude of deformation varied between cells, indicating differences in either load transmission through the matrix or the mechanical properties of individual cells. Under tensile loading the reorganisation of the elastin network differed from a homogeneous elastic response, indicating that it forms a functional structure. CONCLUSIONS: This study highlights the complexity of superficial zone mechanics and demonstrates that the response of the collagen matrix, elastin fibres and chondrocytes are all heterogeneous on the microscopic scale.Arthritis Research U

Strategic Operations Research and the Edelman Prize Finalist Applications 1989-1998

In an earlier study we examined the available evidence on the Edelman Prize finalist applications 1989-1998. This study concluded that 13 of the 42 private sector applications provide examples of strategic operations research (SOR) when SOR is defined as operations research that creates a sustainable competitive advantage. In a follow-up study we tested our classifications, gathering longitudinal information on the continued success of the Edelman applications. We contacted people who were familiar with all the private sector applications that were Edelman finalists 1989-1996 and had at least five years of history since the competition. We describe the post-Edelman history of these applications and use this data to reassess their strategic role. We found that the longitudinal data provides evidence to support our original classification, but also suggests that several additional applications were more strategic than was originally apparent. We conclude that almost 60% (20 of 34) of these applications created a sustainable competitive advantage for their firms and provide examples of SOR

The structure and micromechanics of elastic tissue.

Journal ArticleReviewElastin is a major component of tissues such as lung and blood vessels, and endows them with the long-range elasticity necessary for their physiological functions. Recent research has revealed the complexity of these elastin structures and drawn attention to the existence of extensive networks of fine elastin fibres in tissues such as articular cartilage and the intervertebral disc. Nonlinear microscopy, allowing the visualization of these structures in living tissues, is informing analysis of their mechanical properties. Elastic fibres are complex in composition and structure containing, in addition to elastin, an array of microfibrillar proteins, principally fibrillin. Raman microspectrometry and X-ray scattering have provided new insights into the mechanisms of elasticity of the individual component proteins at the molecular and fibrillar levels, but more remains to be done in understanding their mechanical interactions in composite matrices. Elastic tissue is one of the most stable components of the extracellular matrix, but impaired mechanical function is associated with ageing and diseases such as atherosclerosis and diabetes. Efforts to understand these associations through studying the effects of processes such as calcium and lipid binding and glycation on the mechanical properties of elastin preparations in vitro have produced a confusing picture, and further efforts are required to determine the molecular basis of such effects.British Heart FoundationArthritis U

Social Determinants of Health: Underreported Heterogeneity in Systematic Reviews of Caregiver Interventions.

BACKGROUND AND OBJECTIVES:Although most people have some experience as caregivers, the nature and context of care are highly variable. Caregiving, socioeconomic factors, and health are all interrelated. For these reasons, caregiver interventions must consider these factors. This review examines the degree to which caregiver intervention research has reported and considered social determinants of health. RESEARCH DESIGN AND METHODS:We examined published systematic reviews and meta-analyses of interventions for older adults with age-related chronic conditions using the PRISMA and AMSTAR 2 checklists. From 2,707 papers meeting search criteria, we identified 197 potentially relevant systematic reviews, and selected 33 for the final analysis. RESULTS:We found scant information on the inclusion of social determinants; the papers lacked specificity regarding race/ethnicity, gender, sexual identity, socioeconomic status, and geographic location. The majority of studies focused on dementia, with other conditions common in later life vastly underrepresented. DISCUSSION AND IMPLICATIONS:Significant gaps in evidence persist, particularly for interventions targeting diverse conditions and populations. To advance health equity and improve the effectiveness of interventions, research should address caregiver heterogeneity and improve assessment, support, and instruction for diverse populations. Research must identify aspects of heterogeneity that matter in intervention design, while recognizing opportunities for common elements and strategies

Visual Interactive Simulation: History, Recent Developments, and Major Issues

Visual Interactive Simulation (VIS) has dominated discrete-event simulation in the United Kingdom throughout the eighties. Conceived and initially implemented by Hurrion, who also coined the phrase, VIS first gained widespread exposure through the package SEE-WHY. The ideas behind VIS are fundamentally different from what is referred to in the United States as animation, since the prime motivater is user interaction with the running simulation, rather than just portrayal of the simulation. This paper presents a short history of VIS, and discusses some of the research and development that has been undertaken in the the United Kingdom and North America. Following presentation of an example of VIS, the state of VIS is discussed, and a number of generally accepted guidelines for doing VIS are presented. a number of recent developments in VIS, many of them also relevant to animation, are discussed, and four major issues in the research and practice of VIS are presented

C and N Abundances in Stars At the Base of the Red Giant Branch in M5

We present an analysis of a large sample of moderate resolution Keck LRIS spectra of subgiant (V \sim 17.2) and fainter stars in the Galactic globular cluster M5 (NGC 5904) with the goal of deriving C and N abundances. Star-to-star stochastic variations with significant range in both [C/Fe] and [N/Fe] are found at all luminosities extending to the bottom of the RGB at M_V \sim +3. Similar variations in CH appear to be present in the main sequence turnoff spectra. There is no sign of a change in the behavior of C and N with evolutionary stage over the full range in luminosity of the RGB and SGB. The C and N abundances appear strongly anti-correlated, as would be expected from the CN-cycle processing of stellar material. Yet the present stars are considerably fainter than the RGB bump, the point at which deep mixing is believed to set in. On this basis, while the observed abundance pattern is consistent with proton capture nucleosynthesis, we infer that the site of the reactions is likely not within the present sample, but rather in a population of more massive (2 -- 5 M(Sun)) now defunct stars. The range of variation of the N abundances is very large and the sum of C+N increases as C decreases. To reproduce this requires the incorporation not only of CN but also of ON-processed material. Furthermore, the existence of this correlation is quite difficult to reproduce with an external mechanism such as ``pollution'' with material processed in a more massive AGB star, which mechanism is fundamentally stochastic in nature. We therefore suggest that although the internal mixing hypothesis has serious flaws,new theoretical insights are needed and it should not be ruled out yet. (abridged)Comment: Slightly updated version to conform to that accepted by the A

PHYLOGENY OF ACRIDOCARPUS-BRACHYLOPHON (MALPIGHIACEAE): IMPLICATIONS FOR TERTIARY TROPICAL FLORAS AND AFROASIAN BIOGEOGRAPHY

A major tenet of African Tertiary biogeography posits that lowland rainforest dominated much of Africa in the late Cretaceous and was replaced by xeric vegetation as a response to continental uplift and consequent widespread aridification beginning in the late Paleogene. The aridification of Africa is thought to have been a major factor in the extinction of many African humid-tropical lineages, and in the present-day disparity of species diversity between Africa and other tropical regions. This primarily geologically based model can be tested with independent phylogenetic evidence from widespread African plant groups containing both humid- and xeric-adapted species. We estimated the phylogeny and lineage divergence times within one such angiosperm group, the acridocarpoid clade (Malpighiaceae), with combined ITS, ndhF , and trnL-F data from 15 species that encompass the range of morphological and geographic variation within the group. Dispersal-vicariance analysis and divergence-time estimates suggest that the basal acridocarpoid divergence occurred between African and Southeast Asian lineages approximately 50 million years ago (mya), perhaps after a southward ancestral retreat from high-latitude tropical forests in response to intermittent Eocene cooling. Dispersion of Acridocarpus from Africa to Madagascar is inferred between approximately 50 and 35 mya, when lowland humid tropical forest was nearly continuous between these landmasses. A single dispersal event within Acridocarpus is inferred from western Africa to eastern Africa between approximately 23 and 17 mya, coincident with the widespread replacement of humid forests by savannas in eastern Africa. Although the spread of xeric environments resulted in the extinction of many African plant groups, our data suggest that for others it provided an opportunity for further diversification.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72798/1/j.0014-3820.2002.tb00165.x.pd

Lithium alters brain activation in bipolar disorder in a task- and state-dependent manner: an fMRI study

BACKGROUND: It is unknown if medications used to treat bipolar disorder have effects on brain activation, and whether or not any such changes are mood-independent. METHODS: Patients with bipolar disorder who were depressed (n = 5) or euthymic (n = 5) were examined using fMRI before, and 14 days after, being started on lithium (as monotherapy in 6 of these patients). Patients were examined using a word generation task and verbal memory task, both of which have been shown to be sensitive to change in previous fMRI studies. Differences in blood oxygenated level dependent (BOLD) magnitude between the pre- and post-lithium results were determined in previously defined regions of interest. Severity of mood was determined by the Hamilton Depression Scale for Depression (HAM-D) and the Young mania rating scale (YMRS). RESULTS: The mean HAM-D score at baseline in the depressed group was 15.4 ± 0.7, and after 2 weeks of lithium it was 11.0 ± 2.6. In the euthymic group it was 7.6 ± 1.4 and 3.2 ± 1.3 respectively. At baseline mean BOLD signal magnitude in the regions of interest for the euthymic and depressed patients were similar in both the word generation task (1.56 ± 0.10 and 1.49 ± 0.10 respectively) and working memory task (1.02 ± 0.04 and 1.12 ± 0.06 respectively). However, after lithium the mean BOLD signal decreased significantly in the euthymic group in the word generation task only (1.56 ± 0.10 to 1.00 ± 0.07, p < 0.001). Post-hoc analysis showed that these differences were statistically significant in Broca's area, the left pre-central gyrus, and the supplemental motor area. CONCLUSION: This is the first study to examine the effects of lithium on brain activation in bipolar patients. The results suggest that lithium has an effect on euthymic patients very similar to that seen in healthy volunteers. The same effects are not seen in depressed bipolar patients, although it is uncertain if this lack of change is linked to the lack of major improvements in mood in this group of patients. In conclusion, this study suggests that lithium may have effects on brain activation that are task- and state-dependent. Given the small study size and the mildness of the patient's depression these results require replication