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The use of Alzheimer disease medication for the treatment of dementia symptoms has shown significant benefits with regards to functional and cognitive outcomes as well as nursing home placement (NHP) and mortality. Hospitalisations in these patient groups are characterised by extended length of stays (LOS), frequent readmissions, frequent NHP and high-mortality rates. The impact of Alzheimer disease medication on the aforementioned outcomes remains still unknown. This study assessed the association of Alzheimer disease medication with outcomes of hospitalisation among patients with Alzheimer disease and other forms of dementia.
A dynamic retrospective cohort study from 2004 to 2015 was conducted which claims data from a German health insurance company. People with dementia (PWD) were identified using ICD-10 codes and diagnostic measures. The main predictor of interest was the use of Alzheimer disease medication. Hospitalisation outcomes included LOS, readmissions, NHP and mortality during and after hospitalisation across four hospitalisations. Confounding was addressed using a propensity score throughout all analyses.
A total of 1380 users of Alzheimer disease medication and 6730 non-users were identified. The use of Alzheimer disease medication was associated with significantly shorter LOS during the first hospitalisations with estimates for the second, third and fourth showed a tendency towards shorter hospital stays. In addition, current users of Alzheimer disease medication had a lower risk of hospital readmission after the first two hospitalisations. These associations were not significant for the third and fourth hospitalisations. Post-hospitalisation NHP and mortality rates also tended to be lower among current users than among non-users but differences did not reach statistical significance.
Our results indicate that Alzheimer disease medication might contribute to a reduction of the LOS and the number of readmissions in PWD.
Giant electromagnetic pulses (EMP) generated during the interaction of high-power lasers with solid targets can seriously degrade electrical measurements and equipment. EMP emission is caused by the acceleration of hot electrons inside the target, which produce radiation across a wide band from DC to terahertz frequencies. Improved understanding and control of EMP is vital as we enter a new era of high repetition rate, high intensity lasers (e.g. the Extreme Light Infrastructure). We present recent data from the VULCAN laser facility that demonstrates how EMP can be readily and effectively reduced. Characterization of the EMP was achieved using B-dot and D-dot probes that took measurements for a range of different target and laser parameters. We demonstrate that target stalk geometry, material composition, geodesic path length and foil surface area can all play a significant role in the reduction of EMP. A combination of electromagnetic wave and 3D particle-in-cell simulations is used to inform our conclusions about the effects of stalk geometry on EMP, providing an opportunity for comparison with existing charge separation models.
We derive mass changes of the Greenland ice sheet (GIS) for 2003–07 from ICESat laser altimetry and compare them with results for 1992–2002 from ERS radar and airborne laser altimetry. The GIS continued to grow inland and thin at the margins during 2003–07, but surface melting and accelerated flow significantly increased the marginal thinning compared with the 1990s. The net balance changed from a small loss of 7 ± 3 Gt a−1 in the 1990s to 171 ± 4 Gt a−1 for 2003–07, contributing 0.5 mm a−1 to recent global sea-level rise. We divide the derived mass changes into two components: (1) from changes in melting and ice dynamics and (2) from changes in precipitation and accumulation rate. We use our firn compaction model to calculate the elevation changes driven by changes in both temperature and accumulation rate and to calculate the appropriate density to convert the accumulation-driven changes to mass changes. Increased losses from melting and ice dynamics (17–206 Gt a−1) are over seven times larger than increased gains from precipitation (10–35 Gt a−1) during a warming period of ∼2 K (10 a)−1 over the GIS. Above 2000 m elevation, the rate of gain decreased from 44 to 28 Gt a−1, while below 2000 m the rate of loss increased from 51 to 198 Gt a−1. Enhanced thinning below the equilibrium line on outlet glaciers indicates that increased melting has a significant impact on outlet glaciers, as well as accelerating ice flow. Increased thinning at higher elevations appears to be induced by dynamic coupling to thinning at the margins on decadal timescales.
Changes in ice mass are estimated from elevation changes derived from 10.5 years (Greenland) and 9 years (Antarctica) of satellite radar altimetry data from the European Remote-sensing Satellites ERS-1 and -2. For the first time, the dH/dt values are adjusted for changes in surface elevation resulting from temperature-driven variations in the rate of firn compaction. The Greenland ice sheet is thinning at the margins (–42 ± 2Gta¯1 below the equilibrium-line altitude (ELA)) and growing inland (+53 ± 2Gta-1 above the ELA) with a small overall mass gain (+11 ± 3Gta–1; –0.03 mma–1 SLE (sea-level equivalent)). The ice sheet in West Antarctica (WA) is losing mass (–47 ± 4Gta–1) and the ice sheet in East Antarctica (EA) shows a small mass gain (+16 ± 11 Gta–1) for a combined net change of –31 ± 12 Gta–1 (+0.08mma–1 SLE). The contribution of the three ice sheets to sea level is +0.05±0.03mma–1. The Antarctic ice shelves show corresponding mass changes of –95 ± 11 Gta–1 in WA and +142 ± 10Gta–1 in EA. Thinning at the margins of the Greenland ice sheet and growth at higher elevations is an expected response to increasing temperatures and precipitation in a warming climate. The marked thinnings in the Pine Island and Thwaites Glacier basins of WA and the Totten Glacier basin in EA are probably ice- dynamic responses to long-term climate change and perhaps past removal of their adjacent ice shelves. The ice growth in the southern Antarctic Peninsula and parts of EA may be due to increasing precipitation during the last century.
Mass changes of the Antarctic ice sheet impact sea-level rise as climate changes, but recent rates have been uncertain. Ice, Cloud and land Elevation Satellite (ICESat) data (2003–08) show mass gains from snow accumulation exceeded discharge losses by 82 ± 25 Gt a−1, reducing global sea-level rise by 0.23 mm a−1. European Remote-sensing Satellite (ERS) data (1992–2001) give a similar gain of 112 61 Gt a−1. Gains of 136 Gt a−1 in East Antarctica (EA) and 72 Gt a−1 in four drainage systems (WA2) in West Antarctic (WA) exceed losses of 97 Gt a−1 from three coastal drainage systems (WA1) and 29 Gt a−1 from the Antarctic Peninsula (AP). EA dynamic thickening of 147 Gt a−1 is a continuing response to increased accumulation (>50%) since the early Holocene. Recent accumulation loss of 11 Gt a−1 in EA indicates thickening is not from contemporaneous snowfall increases. Similarly, the WA2 gain is mainly (60 Gt a−1) dynamic thickening. In WA1 and the AP, increased losses of 66 ± 16 Gt a−1 from increased dynamic thinning from accelerating glaciers are 50% offset by greater WA snowfall. The decadal increase in dynamic thinning in WA1 and the AP is approximately one-third of the long-term dynamic thickening in EA and WA2, which should buffer additional dynamic thinning for decades.
Seasonal mean changes in the surface elevation of the ablation zone of West Greenland to 72°N between spring 1985 and summer 1986 are measured using radar altimeter data from the 18-month Geosat Geodetic Mission. Semi-variograms are used to estimate the noise in the data as a function of position on the ice sheet. Mean elevation changes are computed by averaging the elevation differences measured at points where orbits ascending in latitude are later crossed by orbits descending in latitude (or the reverse), with each cross-over difference weighted in proportion to the inverse square of the noise level in the neighborhood of the cross-over point. The mean surface elevation of the ablation zone, relative to spring 1985, ranged from 1.5 ± 0.6 m lower during summer 1985 to 1.7 ± 0.4 m higher during spring 1986.
Clinicians need guidance to address the heterogeneity of treatment responses of patients with major depressive disorder (MDD). While prediction schemes based on symptom clustering and biomarkers have so far not yielded results of sufficient strength to inform clinical decision-making, prediction schemes based on big data predictive analytic models might be more practically useful.
We review evidence suggesting that prediction equations based on symptoms and other easily-assessed clinical features found in previous research to predict MDD treatment outcomes might provide a foundation for developing predictive analytic clinical decision support models that could help clinicians select optimal (personalised) MDD treatments. These methods could also be useful in targeting patient subsamples for more expensive biomarker assessments.
Approximately two dozen baseline variables obtained from medical records or patient reports have been found repeatedly in MDD treatment trials to predict overall treatment outcomes (i.e., intervention v. control) or differential treatment outcomes (i.e., intervention A v. intervention B). Similar evidence has been found in observational studies of MDD persistence-severity. However, no treatment studies have yet attempted to develop treatment outcome equations using the full set of these predictors. Promising preliminary empirical results coupled with recent developments in statistical methodology suggest that models could be developed to provide useful clinical decision support in personalised treatment selection. These tools could also provide a strong foundation to increase statistical power in focused studies of biomarkers and MDD heterogeneity of treatment response in subsequent controlled trials.
Coordinated efforts are needed to develop a protocol for systematically collecting information about established predictors of heterogeneity of MDD treatment response in large observational treatment studies, applying and refining these models in subsequent pragmatic trials, carrying out pooled secondary analyses to extract the maximum amount of information from these coordinated studies, and using this information to focus future discovery efforts in the segment of the patient population in which continued uncertainty about treatment response exists.
In the study of grain boundary migration of metallic materials using molecular dynamics simulation (MDS), grain boundary mobilities and activation energies are often found to be different from experimentally observed values. To reconcile the discrepancies, tremendous effort has been made to replicate experiment conditions in MDS, e.g.as low a driving force as possible, near zero grain boundary velocity. In the present study, we propose an analytic method that removes effects from non-physical conditions such as high driving force or high temperature. The analytic model presumes that two types of rate limiting events coexist during grain boundary migration. Kinetics parameters, such as activation energies, of the rare events are different and therefore should be modeled separately. Activation energies from this model are closer to experiment than previously reported values. Further, by analyzing the evolution of atomic structures, these two types of rate limiting events correspond to shear coupled migration and grain boundary sliding mechanisms, respectively.
Hydrothermal nanoparticle synthesis uses high temperature and pressure water to control the chemical processes that lead to specific compositions and structures. Analyses of the chemistry associated with this process have been mainly restricted to bulk thermodynamics in the form of quantities such as solubilities and empirical models based on experimental observations. In this paper we demonstrate for NiO and NiFe2O4 particles how effective reference chemical potentials derived from first principles calculations can be used to predict cluster shapes, nucleation barriers and surface reactivity. Implications for controlling the nanoparticle size and shape by adjusting pH and temperature will be discussed, as well as implications of these results in forming nanostructured materials by cluster condensation.
Traumatic brain injury (TBI) is prevalent among many populations and existing data suggest that those with TBI are at increased risk for death by suicide. This systematic review serves as an update to a previous review, with the aim of evaluating the current state of evidence regarding prevalence and risk of suicide deaths, post-TBI suicidal ideation and suicide attempts, and treatments to reduce suicide-related outcomes among TBI survivors. Review procedures followed the PRISMA statement guidelines. In all, 1014 abstracts and 83 full-text articles were reviewed to identify 16 studies meeting inclusion criteria. Risk of bias for individual studies ranged from low to high, and very few studies were designed to examine a priori hypotheses related to suicide outcomes of interest. Overall, findings from this systematic review supported an increased risk of suicide among TBI survivors compared to those with no history of TBI. Evidence pertaining to suicidal thoughts and attempts was less clear, mainly due to heterogeneity of methodological quality across studies. One small randomised controlled trial was identified that targeted suicide prevention in TBI survivors. Further research is needed to identify the prevalence of post-TBI ideation and attempts, and to establish evidence-based suicide prevention practices among TBI survivors.
Dogs can be infected by a wide range of Bartonella spp., but limited studies have been conducted in tropical urban and rural dog populations. We aimed to determine Bartonella antibody prevalence in 455 domestic dogs from four tropical countries and detect Bartonella DNA in a subset of these dogs. Bartonella antibodies were detected in 38 (8·3%) dogs, including 26 (10·1%) from Colombia, nine (7·6%) from Brazil, three (5·1%) from Sri Lanka and none from Vietnam. DNA extraction was performed for 26 (63%) of the 41 seropositive and 10 seronegative dogs. Four seropositive dogs were PCR positive, including two Colombian dogs, infected with B. rochalimae and B. vinsonii subsp. berkhoffii, and two Sri Lankan dogs harbouring sequences identical to strain HMD described in dogs from Italy and Greece. This is the first detection of Bartonella infection in dogs from Colombia and Sri Lanka and identification of Bartonella strain HMD from Asia.
Newly developed empirical hydrocarbon potentials and self-consistent first-principles local density functional methods are used to investigate possible isomers and the electronic structure of C60H36. Within the high symmetry Th structure conjectured by the groups at Rice University there are two inequivalent sets of hydrogen atoms containing twelve and twenty-four atoms respectively. Binding each set either inside or outside of the C60 cage leads to four isomers of C60H36 with inequivalent strain energies. Although we find that placing twelve hydrogens inside the cage can lead to a metastable structure, our calculated total energies suggest that the isomer with all the hydrogens on the outside of the cage is the energetically most stable.
Recent reports suggest that graphitic tubules with diameters on the order of fullerene diameters have been synthesized. Such small-diameter tubules should have electronic properties related to those of two-dimensional graphite. We demonstrate by comparison with results from a first-principles, self-consistent, all-electron Gaussian-orbital based local-density functional approach that an all-valence tight-binding model can be expected to give a reasonable description of the electronic states of these tubules. In analyzing both high-symmetry tubules and lower-symmetry chiral tubules, we see that a relatively high carrier density could be expected for many of these structures.
We have calculated the electronic structure of icosahedrai C60H60 and tetrahedral C60H60 via an all-electron Gaussian-orbital based local-density functional approach. The one-electron wavefunctions and eigenvalues have been used in a first-order time-dependent perturbation theoretic calculation of the spherically averaged X-ray and ultraviolet pho-toemission cross-sections for these molecules.
We present a simulation studying the initiation of a model energetic molecular solid. For low-velocity, massive flyer-plate impact, the model detonation initiates behind a compaction shock. This detonation front subsequently overtakes the compaction shock exhibiting a behavior qualitatively similar to that observed in experminental studies of homogeneous initiation and delayed detonation from low velocity impact.
We present a comparative study of two different chemically-sustained shock waves. One shows behavior expected from the Zel'dovich, von Neumann, and Doering (ZND) continuum theory of planar detonations. The other exhibits the complexity of a split shock wave resulting from the presence of a polymorphic phase transition. This comparative study demonstrates the importance of carefully considering the high-pressure characteristics of the model in developing potentials for simulating detonations. This comparative study also raises the fascinating possibility of a first-order phase transition accompanying a condensed-phase detonation.
The short length and time scales associated with chemical detonations make these processes excellent candidates for study by MD simulation. Potentials used in these simulations must have sufficient flexibility to describe gas-phase properties of isolated reactant and product molecules, high density material generated under shock compression, and allow smooth adjustment of bonding forces during chemical reaction. The REBO formalism has been shown to provide these characteristics and allow the treatment of a sufficient number atoms for sufficiently long times to demonstrate a chemically-sustained shock wave (CSSW). In this paper we present a REBO potential describing the oxygen system for use in MD simulation of detonation in an ozone molecular solid. The potential reproduces spectroscopic properties of isolated gas-phase O2 and O3. It also describes an ozone molecular solid with density and speed of sound within physical norms. We observe detonation characteristics that depend on crystallographic orientation in simulations using a three dimensional ozone molecular crystal.
Palynological studies document forest disappearance during the late Holocene in the tropical Maya lowlands of northern Guatemala. The question remains as to whether this vegetation change was driven exclusively by anthropogenic deforestation, as previously suggested, or whether it was partly attributable to climate changes. We report multiple palaeoclimate and palaeoenvironment proxies (pollen, geochemical, sedimentological) from sediment cores collected in Lake Petén Itzá, northern Guatemala. Our data indicate that the earliest phase of late Holocene tropical forest reduction in this area started at ∼ 4500 cal yr BP, simultaneous with the onset of a circum-Caribbean drying trend that lasted for ∼ 1500 yr. This forest decline preceded the appearance of anthropogenically associated Zea mays pollen. We conclude that vegetation changes in Petén during the period from ∼ 4500 to ∼ 3000 cal yr BP were largely a consequence of dry climate conditions. Furthermore, palaeoclimate data from low latitudes in North Africa point to teleconnective linkages of this drying trend on both sides of the Atlantic Ocean.