High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular mortality.

AIMS High-density lipoprotein (HDL) cholesterol is a strong predictor of cardiovascular mortality. This work aimed to investigate whether the presence of coronary artery disease (CAD) impacts on its predictive value. METHODS AND RESULTS We studied 3141 participants (2191 males, 950 females) of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean ± standard deviation age of 62.6 ± 10.6 years, body mass index of 27.5 ± 4.1 kg/m², and HDL cholesterol of 38.9 ± 10.8 mg/dL. The cohort consisted of 699 people without CAD, 1515 patients with stable CAD, and 927 patients with unstable CAD. The participants were prospectively followed for cardiovascular mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A total of 590 participants died from cardiovascular diseases. High-density lipoprotein cholesterol by tertiles was inversely related to cardiovascular mortality in the entire cohort (P = 0.009). There was significant interaction between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In stratified analyses, HDL cholesterol was strongly associated with cardiovascular mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18-0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95% CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI) = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in 3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER cohort, and by a meta-analysis comprising all three cohorts. CONCLUSION The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patients.

Avoidable hospitalizations in Switzerland: a small area analysis on regional variation, density of physicians, hospital supply and rurality.

BACKGROUND Avoidable hospitalizations (AH) are hospital admissions for diseases and conditions that could have been prevented by appropriate ambulatory care. We examine regional variation of AH in Switzerland and the factors that determine AH. METHODS We used hospital service areas, and data from 2008-2010 hospital discharges in Switzerland to examine regional variation in AH. Age and sex standardized AH were the outcome variable, and year of admission, primary care physician density, medical specialist density, rurality, hospital bed density and type of hospital reimbursement system were explanatory variables in our multilevel poisson regression. RESULTS Regional differences in AH were as high as 12-fold. Poisson regression showed significant increase of all AH over time. There was a significantly lower rate of all AH in areas with more primary care physicians. Rates increased in areas with more specialists. Rates of all AH also increased where the proportion of residences in rural communities increased. Regional hospital capacity and type of hospital reimbursement did not have significant associations. Inconsistent patterns of significant determinants were found for disease specific analyses. CONCLUSION The identification of regions with high and low AH rates is a starting point for future studies on unwarranted medical procedures, and may help to reduce their incidence. AH have complex multifactorial origins and this study demonstrates that rurality and physician density are relevant determinants. The results are helpful to improve the performance of the outpatient sector with emphasis on local context. Rural and urban differences in health care delivery remain a cause of concern in Switzerland.

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

UNLABELLED Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.

Estimating population and livestock density of mobile pastoralists and sedentary settlements in the southeastern Lake Chad area

Mobile pastoralists provide major contributions to the gross domestic product in Chad, but little information is available regarding their demography. The Lake Chad area population is increasing, resulting in competition for scarce land and water resources. For the first time, the density of people and animals from mobile and sedentary populations was assessed using randomly defined sampling areas. Four sampling rounds were conducted over two years in the same areas to show population density dynamics. We identified 42 villages of sedentary communities in the sampling zones; 11 (in 2010) and 16 (in 2011) mobile pastoralist camps at the beginning of the dry season and 34 (in 2011) and 30 (in 2012) camps at the end of the dry season. A mean of 64.0 people per km2 (95% confidence interval, 20.3-107.8) were estimated to live in sedentary villages. In the mobile communities, we found 5.9 people per km2 at the beginning and 17.5 people per km2 at the end of the dry season. We recorded per km2 on average 21.0 cattle and 31.6 small ruminants in the sedentary villages and 66.1 cattle and 102.5 small ruminants in the mobile communities, which amounts to a mean of 86.6 tropical livestock units during the dry season. These numbers exceed, by up to five times, the published carrying capacities for similar Sahelian zones. Our results underline the need for a new institutional framework. Improved land use management must equally consider the needs of mobile communities and sedentary populations.

Temperature Prediction Model for Bone Drilling Based on Density Distribution and In Vivo Experiments for Minimally Invasive Robotic Cochlear Implantation

Surgical robots have been proposed ex vivo to drill precise holes in the temporal bone for minimally invasive cochlear implantation. The main risk of the procedure is damage of the facial nerve due to mechanical interaction or due to temperature elevation during the drilling process. To evaluate the thermal risk of the drilling process, a simplified model is proposed which aims to enable an assessment of risk posed to the facial nerve for a given set of constant process parameters for different mastoid bone densities. The model uses the bone density distribution along the drilling trajectory in the mastoid bone to calculate a time dependent heat production function at the tip of the drill bit. Using a time dependent moving point source Green's function, the heat equation can be solved at a certain point in space so that the resulting temperatures can be calculated over time. The model was calibrated and initially verified with in vivo temperature data. The data was collected in minimally invasive robotic drilling of 12 holes in four different sheep. The sheep were anesthetized and the temperature elevations were measured with a thermocouple which was inserted in a previously drilled hole next to the planned drilling trajectory. Bone density distributions were extracted from pre-operative CT data by averaging Hounsfield values over the drill bit diameter. Post-operative [Formula: see text]CT data was used to verify the drilling accuracy of the trajectories. The comparison of measured and calculated temperatures shows a very good match for both heating and cooling phases. The average prediction error of the maximum temperature was less than 0.7 °C and the average root mean square error was approximately 0.5 °C. To analyze potential thermal damage, the model was used to calculate temperature profiles and cumulative equivalent minutes at 43 °C at a minimal distance to the facial nerve. For the selected drilling parameters, temperature elevation profiles and cumulative equivalent minutes suggest that thermal elevation of this minimally invasive cochlear implantation surgery may pose a risk to the facial nerve, especially in sclerotic or high density mastoid bones. Optimized drilling parameters need to be evaluated and the model could be used for future risk evaluation.

Mapping tree density at a global scale

The global extent and distribution of forest trees is central to our understanding of the terrestrial biosphere. We provide the first spatially continuous map of forest tree density at a global scale. This map reveals that the global number of trees is approximately 3.04 trillion, an order of magnitude higher than the previous estimate. Of these trees, approximately 1.39 trillion exist in tropical and subtropical forests, with 0.74 trillion in boreal regions and 0.61 trillion in temperate regions. Biome-level trends in tree density demonstrate the importance of climate and topography in controlling local tree densities at finer scales, as well as the overwhelming effect of humans across most of the world. Based on our projected tree densities, we estimate that over 15 billion trees are cut down each year, and the global number of trees has fallen by approximately 46% since the start of human civilization.

Standard model cross-over on the lattice

With the physical Higgs mass the standard model symmetry restoration phase transition is a smooth cross-over. We study the thermodynamics of the cross-over using numerical lattice Monte Carlo simulations of an effective SU(2)×U(1) gauge+Higgs theory, significantly improving on previously published results. We measure the Higgs field expectation value, thermodynamic quantities like pressure, energy density, speed of sound and heat capacity, and screening masses associated with the Higgs and Z fields. While the cross-over is smooth, it is very well defined with a width of only ∼5  GeV. We measure the cross-over temperature from the maximum of the susceptibility of the Higgs condensate, with the result Tc=159.5±1.5  GeV. Outside of the narrow cross-over region the perturbative results agree well with nonperturbative ones.

Density-dependent dynamics of a dominant rain forest tree change with juvenile stage and time of masting

Although negative density dependence (NDD) can facilitate tree species coexistence in forests, the underlying mechanisms can differ, and rarely are the dynamics of seedlings and saplings studied together. Herein we present and discuss a novel mechanism based on our investigation of NDD predictions for the large, grove-forming ectomycorrhizal mast fruiting tree, Microberlinia bisulcata (Caesalpiniaceae), in an 82.5-ha plot at Korup, Cameroon. We tested whether juvenile density, size, growth and survival decreases with increasing conspecific adult basal area for 3245 ‘new’ seedlings and 540 ‘old’ seedlings (< 75-cm tall) during an approximately 4-year study period (2008–2012) and for 234 ‘saplings’ (≥ 75-cm tall) during an approximately 6-year study period (2008–2014). We found that the respective densities of new seedlings, old seedlings and saplings were positively, not and negatively related to increasing BA. Maximum leaf numbers and heights of old seedlings were negatively correlated with increasing basal areas, as were sapling heights and stem diameters. Whereas survivorship of new seedlings decreased by more than one-half with increasing basal area over its range in 2010–2012, that of old seedlings decreased by almost two-thirds, but only in 2008–2010, and was generally unrelated to conspecific seedling density. In 2010–2012 relative growth rates in new seedlings’ heights decreased with increasing basal area, as well as with increasing seedling density, together with increasing leaf numbers, whereas old seedlings’ growth was unrelated to either conspecific density or basal area. Saplings of below-average height had reduced survivorship with increasing basal area (probability decreasing from approx. 0.4 to 0.05 over the basal area range tested), but only sapling growth in terms of leaf numbers decreased with increasing basal area. These static and dynamic results indicate that NDD is operating within this system, possibly stabilizing the M. bisulcata population. However, these NDD patterns are unlikely to be caused by symmetric competition or by consumers. Instead, an alternative mechanism for conspecific adult–juvenile negative feedback is proposed, one which involves the interaction between tree phenology and ectomycorrhizal linkages.

Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years

Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.