Ontogenetic changes in femoral cross-sectional geometry during childhood locomotor development

Objectives: The femur is a major weight-bearing bone that is variably loaded throughout growth as children transition through locomotory states prior to the attainment of a mature bipedal gait. Here, we document ontogenetic trends in femoral cross-sectional geometry (CSG) and explore how changes in loading regime may impact the structural arrangement of cortical bone along the length of the developing diaphysis. Materials and methods: Micro-CT scans of 110 immature femora were generated from a documented archaeological sample ranging in age from birth to 8.5 years old. CSG properties indicative of relative bone strength and bending rigidity were analyzed from cross-sections extracted at 35%, 50% and 65% of total intermetaphyseal length. Results: Infants experience a marked redistribution of cortical bone between birth and 7 months facilitating a more advantageous mechanical structure for early load bearing behaviors as bone is displaced further from the section centroid. Early walkers are characterized by a mediolaterally reinforced cross-section that becomes more circular as gait continues to develop. Discussion: During ontogeny the femur undergoes distinct morphological phases, which correspond with changes in loading regime. This study illustrates the importance of loading conditions in shaping immature bone morphology. Nonmechanical factors such as changes in hormonal environmental can also impact on this dynamic

Dynamic response of a thin sessile drop of conductive liquid to an abruptly applied or removed electric field

We consider, both theoretically and experimentally, a thin sessile drop of conductive liquid that rests on the lower plate of a parallel-plate capacitor. We derive analytical expressions for both the initial deformation and the relaxation dynamics of the drop as the electric field is either abruptly applied or abruptly removed, as functions of the geometrical, electrical, and material parameters, and investigate the ranges of validity of these expressions by comparison with full numerical simulations. These expressions provide a reasonable description of the experimentally measured dynamic response of a drop of conductive ionic liquid 1-butyl-3-methyl imidazolium tetrafluoroborate

Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease

Background and Aims:We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels 60 mu g/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients. Copyright (C) 2011 S. Karger AG, Base

Multi-Timescale Perceptual History Resolves Visual Ambiguity

When visual input is inconclusive, does previous experience aid the visual system in attaining an accurate perceptual interpretation? Prolonged viewing of a visually ambiguous stimulus causes perception to alternate between conflicting interpretations. When viewed intermittently, however, ambiguous stimuli tend to evoke the same percept on many consecutive presentations. This perceptual stabilization has been suggested to reflect persistence of the most recent percept throughout the blank that separates two presentations. Here we show that the memory trace that causes stabilization reflects not just the latest percept, but perception during a much longer period. That is, the choice between competing percepts at stimulus reappearance is determined by an elaborate history of prior perception. Specifically, we demonstrate a seconds-long influence of the latest percept, as well as a more persistent influence based on the relative proportion of dominance during a preceding period of at least one minute. In case short-term perceptual history and long-term perceptual history are opposed (because perception has recently switched after prolonged stabilization), the long-term influence recovers after the effect of the latest percept has worn off, indicating independence between time scales. We accommodate these results by adding two positive adaptation terms, one with a short time constant and one with a long time constant, to a standard model of perceptual switching

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

A Dynamical Analysis of the Suitability of Prehistoric Spheroids from the Cave of Hearths as Thrown Projectiles

Spheroids are ball-shaped stone objects found in African archaeological sites dating from 1.8 million years ago (Early Stone Age) to at least 70,000 years ago (Middle Stone Age). Spheroids are either fabricated or naturally shaped stones selected and transported to places of use making them one of the longest-used technologies on record. Most hypotheses about their use suggest they were percussive tools for shaping or grinding other materials. However, their size and spherical shape make them potentially useful as projectile weapons, a property that, uniquely, humans have been specialised to exploit for millions of years. Here we show (using simulations of projectile motions resulting from human throwing) that 81% of a sample of spheroids from the late Acheulean (Bed 3) at the Cave of Hearths, South Africa afford being thrown so as to inflict worthwhile damage to a medium-sized animal over distances up to 25 m. Most of the objects have weights that produce optimal levels of damage from throwing, rather than simply being as heavy as possible (as would suit other functions). Our results show that these objects were eminently suitable for throwing, and demonstrate how empirical research on behavioural tasks can inform and constrain our theories about prehistoric artefacts

Evidence for handheld electronic medical records in improving care: a systematic review

BACKGROUND: Handheld electronic medical records are expected to improve physician performance and patient care. To confirm this, we performed a systematic review of the evidence assessing the effects of handheld electronic medical records on clinical care. METHODS: To conduct the systematic review, we searched MEDLINE, EMBASE, CINAHL, and the Cochrane library from 1966 through September 2005. We included randomized controlled trials that evaluated effects on practitioner performance or patient outcomes of handheld electronic medical records compared to either paper medical records or desktop electronic medical records. Two reviewers independently reviewed citations, assessed full text articles and abstracted data from the studies. RESULTS: Two studies met our inclusion criteria. No other randomized controlled studies or non-randomized controlled trials were found that met our inclusion criteria. Both studies were methodologically strong. The studies examined changes in documentation in orthopedic patients with handheld electronic medical records compared to paper charts, and both found an increase in documentation. Other effects noted with handheld electronic medical records were an increase in time to document and an increase in wrong or redundant diagnoses. CONCLUSION: Handheld electronic medical records may improve documentation, but as yet, the number of studies is small and the data is restricted to one group of patients and a small group of practitioners. Further study is required to determine the benefits with handheld electronic medical records especially in assessing clinical outcomes

Tracking of sport and exercise types from midlife to old age: a 20-year cohort study of British men.

Background: Previous physical activity (PA) tracking studies have examined the stability of overall PA and/or PA types, but few have investigated how specific types of sport/exercise track over the life course. The aim of this study was to determine how specific sports/exercises in midlife track and predict future sport/exercise and PA in men transitioning to old age. Methods: Seven thousand seven hundred thirty-five men (aged 40-59 years) recruited in 1978-80 were followed up after 12, 16 and 20 years. At each wave men self-reported participation in sport/exercise. Frequent sport/exercise participants (> 1/month) reported the types of sport/exercise they engaged in. Men also reported total PA, health status, lifestyle behaviours and socio-demographic characteristics. Stability of each sport/exercise was assessed using kappa statistics and intraclass correlation coefficients. Logistic regression estimated the odds of participating in sport/exercise and being active at 20-year follow up according to specific types of sport/exercise in midlife. Results: Three thousand three hundred eighty-four men with complete data at all waves were included in analyses. Tracking of specific sports/exercises ranged from fair to substantial, with golf being the most common and most stable. Bowls was the most frequently adopted. Odds of participating in sport/exercise and being active in old age varied according to sport/exercise types in midlife. Golf and bowls in midlife were the strongest predictors of sport/exercise participation in old age. Golf, cricket and running/jogging in midlife were among the strongest predictors of being active in old age. Compared to participating in just one sport/exercise in midlife, sampling multiple sports/exercises was more strongly associated with sport/exercise participation and being active in old age. Conclusion: The stability of sport/exercise participation from midlife to old age varies by type. Specific sports/exercises in midlife may be more likely to predict future PA than others. However, participating in a range of sports/exercises may be optimal for preserving PA into old age