Research utility of noninvasive methods for measurement of cardiac output

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109853/1/cptclpt198751.pd

Should Species Distribution Models Account for Spatial Autocorrelation? A Test of Model Projections Across Eight Millennia of Climate Change

Aim: The distributions of many organisms are spatially autocorrelated, but it is unclear whether including spatial terms in species distribution models (SDMs) improves projections of species distributions under climate change. We provide one of the first comparative evaluations of the ability of a purely spatial SDM, a purely non-spatial SDM and a SDM that combines spatial and environmental information to project species distributions across eight millennia of climate change. Location: Eastern North America. Methods: To distinguish between the importance of climatic versus spatial explanatory variables we fit three Bayesian SDMs to modern occurrence data for Fagus and Tsuga, two tree genera whose distributions can be reliably inferred from fossil pollen: a spatially varying intercept model, a non-spatial model with climatic variables and a spatially varying intercept plus climate model. Using palaeoclimate data with a high temporal resolution, we hindcasted the SDMs in 1000-year time steps for 8000 years, and compared model projections with palynological data for the same periods. Results: For both genera, spatial SDMs provided better fits to the calibration data, more accurate predictions of a hold-out validation dataset of modern trees and higher variance in current predictions and hindcasted projections than non-spatial SDMs. Performance of non-spatial and spatial SDMs according to the area under the receiver operating curve varied by genus. For both genera, false negative rates between non-spatial and spatial models were similar, but spatial models had lower false positive rates than non-spatial models. Main conclusions: The inclusion of computationally demanding spatial random effects in SDMs may be warranted when ecological or evolutionary processes prevent taxa from shifting their distributions or when the cost of false positives is high.Organismic and Evolutionary Biolog

Importance of overweight in studies of left ventricular hypertrophy and diastolic function in mild systemic hypertension

The relations of Metropolitan Life Insurance Co. Relative Weight values and blood pressure (BP) to minimal forearm vascular resistance, ventricular septal and posterior wall thickness, left ventricular (LV) mass index and cardiac diastolic function were assessed in 31 men, 37 +/- 2 (mean +/-standard error of the mean) years of age. Eighteen patients with untreated mild hypertension were compared with 13 normotensive control subjects of similar age and weight. The hypertensives had higher clinic (137 +/-3/96 +/- 2 vs 121 +/-4/81 +/- 3 mm Hg, p 2). Furthermore, diastolic peak filling rate, an index of LV diastolic function, was virtually identical in the 2 groups (2.71 +/- 0.14 vs 2.69 +/- 0.07 liters/s, difference not significant). Correlates of peak filling rate included relative weight (r = -0.62, p The results suggest that relative weight is an important determinant of diastolic function and LV dimensions. These findings highlight the importance of controlling for weight in comparative studies of cardiovascular structure and function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27747/1/0000139.pd

Sensitive response of the Greenland Ice Sheet to surface melt drainage over a soft bed

This is the accepted manuscript. The final version is available from Nature Communications at http://www.nature.com/ncomms/2014/140929/ncomms6052/full/ncomms6052.html.The dynamic response of the Greenland Ice Sheet (GrIS) depends on feedbacks between surface meltwater delivery to the subglacial environment and ice flow. Recent work has highlighted an important role of hydrological processes in regulating the ice flow, but models have so far overlooked the mechanical effect of soft basal sediment. Here we use a three-dimensional model to investigate hydrological controls on a GrIS soft-bedded region. Our results demonstrate that weakening and strengthening of subglacial sediment, associated with the seasonal delivery of surface meltwater to the bed, modulates ice flow consistent with observations. We propose that sedimentary control on ice flow is a viable alternative to existing models of evolving hydrological systems, and find a strong link between the annual flow stability, and the frequency of high meltwater discharge events. Consequently, the observed GrIS resilience to enhanced melt could be compromised if runoff variability increases further with future climate warming.RCU

Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic RHBMP-2 and anti-resorptive agents

Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs) utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 μg) ± anti-resorptive agents: zoledronic acid (5 μg ZA), ZA pre-adsorbed onto hydroxyapatite microparticles, (5 μg ZA/2 % HA) or IkappaB kinase (IKK) inhibitor (10 μg PS-1145). Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3 % TV, p < 0.01). The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01). Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01). Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation

The 3rd Fermi GBM Gamma-Ray Burst Catalog: The First Six Years

Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two gamma-ray bursts (GRB) every three days. Here we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years, through the middle of July 2014. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300~keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBM's low-energy NaI(Tl) detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fitted by a two-component model with short-hard and long-soft bursts, than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: 225 pages, 13 figures and 8 tables. Accepted for publication in Astrophysical Journal Supplement 201

The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilisation of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. The three candidate mechanisms tested did not explain this organic acid accumulation. Our results link genotype through specific processes to higher-level phenotypes, formalising our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits

General practitioners' evaluation of community psychiatric services: responsiveness to change of the General Practitioner Experiences Questionnaire (GPEQ)

<p>Abstract</p> <p>Background</p> <p>Instruments have been developed to assess professional views of the quality of care but have rarely been tested for responsiveness to change. The objective of this study was to test the responsiveness of the General Practitioner Experiences Questionnaire (GPEQ) for the measurement of Community Mental Health Centres in Norway.</p> <p>Methods</p> <p>National surveys were conducted in Norway in 2006 (n = 2,415) and 2008 (n = 2,209) to measure general practitioners' evaluation of community mental health centres. GPs evaluated the centres by means of a postal questionnaire, consisting of questions focused on centre quality and cooperation with GPs. As part of the national surveys 75 GPs in 2006 and 66 GPs in 2008 evaluated Hamar community mental health centre. Between the surveys, several quality improvement initiatives were implemented which were directed at cooperation with and guidance for GPs in Stange municipality, one of eight municipalities in Hamar centre catchment area. The main outcome measures were changes in GPEQ scores from 2006 to 2008 for GPs evaluating Hamar community mental health centre from Stange municipality, and changes in scores for GPs in the other seven municipalities and nationally which were assessed for statistical significance.</p> <p>Results</p> <p>GPs in Stange municipality rated Hamar community mental health centre significantly better on the guidance scale in 2008 than in 2006; on a 0-100 scale where 100 represents the best possible experiences the score was 26.5 in 2006 and 58.3 in 2008 (p < 0.001). Apart from one item about workforce situation, none of the other scales and items showed significant changes. The control group from the other seven municipalities gave significantly poorer rating for the emergency situation scale, the workforce situation scale and seven items in 2008 than in 2006. The national results showed small differences between 2006 and 2008, even though several scales and items were significantly different. A question about changes in centre performance over the last 2-3 years showed that 82% of GPs from Stange municipality reported that Hamar community mental health centre had improved, compared to only 36% from the other seven municipalities and 40% nationally which was statistically significant.</p> <p>Conclusions</p> <p>Following the implementation of an initiative designed to enhance service quality, the GPEQ identified expected changes in the guidance scale for the intervention group, indicating that the instrument is responsive to change. The worsening of services for GPs in the control group evaluating Hamar centre warrants further study.</p