Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women

Context: Evidence is limited on the effects of different patterns of use of postmenopausal hormone therapy on fracture incidence and particularly on the effects of ceasing use. Objective: To investigate the effect of different patterns of hormone therapy use on fracture incidence. Design, Setting, and Participants: Prospective study of 138737 postmenopausal women aged 50 to 69 years recruited from the UK general population in 19961998 (the Million Women Study) and followed up for 1.9 to 3.9 years (average, 2.8 years) for fracture incidence. Main Outcome Measure: Adjusted relative risk (RR) for incident fracture (except fracture of the fingers, toes, and ribs) in hormone therapy users compared with never users at baseline. Results: A total of 5197 women (3.7%) reported 1 or more fractures, 79% resulting from falls. Current users of hormone therapy at baseline had a significantly reduced incidence of fracture (RR, 0.62; 95% confidence interval [CI], 0.58-0.66; P<.001). This protection was evident soon after hormone therapy began, and the RR decreased with increasing duration of use (P=.001). Among current users at baseline the RR of fracture did not vary significantly according to whether estrogen-only, estrogen-progestin, or other types of hormones were used (RR [95% CI], 0.64 [0.58-0.71], 0.58 [0.53-0.64], and 0.67 [0.56-0.80], respectively; P=19), nor did it vary significantly according to estrogen dose or estrogen or progestin constituents. The RR associated with current use of hormone therapy did not vary significantly according to 11 personal characteristics of study participants, including their age at menopause, body mass index, and physical activity. Past users of hormone therapy at baseline experienced no significant protection against fractures (RR, 1.07; 95% CI, 0.99-1.15); incidence rates returned to those of never-users within about a year of ceasing use. Conclusions: All types of hormone therapy studied confer substantial protection against fracture while they are used. This protection appears rapidly after use commences and wears off rapidly after use ceases. The older women are, the greater is their absolute reduction in fracture incidence while using hormone therapy.

Analysis of the regional pattern of sea level change due to ocean dynamics and density changes for 1993-2099 in observations and CMIP5 AOGCMs

Predictions of twenty-first century sea level change show strong regional variation. Regional sea level change observed by satellite altimetry since 1993 is also not spatially homogenous. By comparison with historical and pre-industrial control simulations using the atmosphere–ocean general circulation models (AOGCMs) of the CMIP5 project, we conclude that the observed pattern is generally dominated by unforced (internal generated) variability, although some regions, especially in the Southern Ocean, may already show an externally forced response. Simulated unforced variability cannot explain the observed trends in the tropical Pacific, but we suggest that this is due to inadequate simulation of variability by CMIP5 AOGCMs, rather than evidence of anthropogenic change. We apply the method of pattern scaling to projections of sea level change and show that it gives accurate estimates of future local sea level change in response to anthropogenic forcing as simulated by the AOGCMs under RCP scenarios, implying that the pattern will remain stable in future decades. We note, however, that use of a single integration to evaluate the performance of the pattern-scaling method tends to exaggerate its accuracy. We find that ocean volume mean temperature is generally a better predictor than global mean surface temperature of the magnitude of sea level change, and that the pattern is very similar under the different RCPs for a given model. We determine that the forced signal will be detectable above the noise of unforced internal variability within the next decade globally and may already be detectable in the tropical Atlantic.

Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease s attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

Analysis of the calving pattern of herds in small-scale dairy systems in central Mexico

This study sets out to find the best calving pattern for small-scale dairy systems in Michoacan State, central Mexico. Two models were built. First, a linear programming model was constructed to optimize calving pattern and herd structure according to metabolizable energy availability. Second, a Markov chain model was built to investigate three reproductive scenarios (good, average and poor) in order to suggest factors that maintain the calving pattern given by the linear programming model. Though it was not possible to maintain the optimal linear programming pattern, the Markov chain model suggested adopting different reproduction strategies according to period of the year that the cow is expected to calve. Comparing different scenarios, the Markov model indicated the effect of calving interval on calving pattern and herd structure.

The glycosylation pattern of baculovirus expressed envelope protein E2 affects its ability to prevent infection with bovine viral diarrhoea virus

We have investigated the role of glycosylation of the envelope glycoprotein E2 of bovine viral diarrhoea virus (BVDV), produced in insect cells, in BVDV infection. When amino acids predicated to code for the C-terminal N-linked glycosylation site were mutated the resulting protein was less efficient than wild type protein at preventing infection of susceptible cells with BVDV. In addition, mutational analysis showed that a further two predicted N-terminal N-linked glycosylation sites of E2 are required for efficient production of recombinant protein. (c) 2005 Elsevier B.V. All rights reserved.

Evidence for a reversal with age in the pattern of near-wall blood flow around aortic branches

The changes that occur with age in the distribution of atherosclerotic lesions around arterial branch points challenge accepted theories relating disease to haemodynamic stresses. We investigated whether flow near branch points changes with age in a way that can account for the different lesion distributions. Flow around 20 branches from immature and mature aortas was investigated by examining the length:width ratio and orientation of endothelial nuclei; these properties depend on the magnitude and direction of near-wall flows, respectively. There were significant changes in the pattern of nuclear shape with age, consistent with a reversal in the pattern of shear around branches. In control regions away from branches, there were no such changes. The role of haemodynamic stresses in atherogenesis may require re-evaluation in the light of these results. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Evidence for a reversal with age in the pattern of near-wall blood flow around aortic branches

The changes that occur with age in the distribution of atherosclerotic lesions around arterial branch points challenge accepted theories relating disease to haemodynamic stresses. We investigated whether flow near branch points changes with age in a way that can account for the different lesion distributions. Flow around 20 branches from immature and mature aortas was investigated by examining the length:width ratio and orientation of endothelial nuclei; these properties depend on the magnitude and direction of near-wall flows, respectively. There were significant changes in the pattern of nuclear shape with age, consistent with a reversal in the pattern of shear around branches. In control regions away from branches, there were no such changes. The role of haemodynamic stresses in atherogenesis may require re-evaluation in the light of these results.

Analysis of chain and blood group type and branching pattern of sialylated oligosaccharides by negative ion electrospray tandem mass spectrometry

We previously reported sequence determination of neutral oligosaccharides by negative ion electrospray tandem mass spectrometry on a quadrupole-orthogonal time-of-flight instrument with high sensitivity and without the need of derivatization. In the present report, we extend our strategies to sialylated oligosaccharides for analysis of chain and blood group types together with branching patterns. A main feature in the negative ion mass spectrometry approach is the unique double glycosidic cleavage induced by 3-glycosidic substitution, producing characteristic D-type fragments which can be used to distinguish the type 1 and type 2 chains, the blood group related Lewis determinants, 3,6-disubstituted core branching patterns, and to assign the structural details of each of the branches. Twenty mono- and disialylated linear and branched oligosaccharides were used for the investigation, and the sensitivity achieved is in the femtomole range. To demonstrate the efficacy of the strategy, we have determined a novel complex disialylated and monofucosylated tridecasaccharide that is based on the lacto-N-decaose core. The structure and sequence assignment was corroborated by :methylation analysis and H-1 NMR spectroscopy.

Low-order dynamical behavior in the martian atmosphere: Diagnosis of general circulation model results

The hypothesis of a low dimensional martian climate attractor is investigated by the application of the proper orthogonal decomposition (POD) to a simulation of martian atmospheric circulation using the UK Mars general circulation model (UK-MGCM). In this article we focus on a time series of the interval between autumn and winter in the northern hemisphere, when baroclinic activity is intense. The POD is a statistical technique that allows the attribution of total energy (TE) to particular structures embedded in the UK-MGCM time-evolving circulation. These structures are called empirical orthogonal functions (EOFs). Ordering the EOFs according to their associated energy content, we were able to determine the necessary number to account for a chosen amount of atmospheric TE. We show that for Mars a large fraction of TE is explained by just a few EOFs (with 90% TE in 23 EOFs), which apparently support the initial hypothesis. We also show that the resulting EOFs represent classical types of atmospheric motion, such as thermal tides and transient waves. Thus, POD is shown to be an efficient method for the identification of different classes of atmospheric modes. It also provides insight into the non-linear interaction of these modes.

Divergent evolutionary pattern of starch biosynthetic pathway genes in grasses and dicots

Starch is the most widespread and abundant storage carbohydrate in crops and its production is critical to both crop yield and quality. As regards the starch content in the seeds of crop plants, there are distinct difference between grasses (Poaceae) and dicots. However, few studies have described the evolutionary pattern of genes in the starch biosynthetic pathway in these two groups of plants. In this study, therefore, an attempt was made to compare the evolutionary rate, gene duplication and selective pattern of the key genes involved in this pathway between the two groups, using five grasses and five dicots as materials. The results showed (i) distinct differences in patterns of gene duplication and loss between grasses and dicots; duplication in grasses mainly occurred prior to the divergence of grasses, whereas duplication mostly occurred in individual species within the dicots; there is less gene loss in grasses than in dicots; (ii) a considerably higher evolutionary rate in grasses than in dicots in most gene families analyzed; (iii) evidence of a different selective pattern between grasses and dicots; positive selection may have occurred asymmetrically in grasses in some gene families, e.g. AGPase small subunit. Therefore, we deduced that gene duplication contributes to, and a higher evolutionary rate is associated with, the higher starch content in grasses. In addition, two novel aspects of the evolution of the starch biosynthetic pathway were observed.