To define and investigate key issues in the management of dementia and to make literature-based treatment recommendations.
The authors searched the literature for four clinical questions: 1) Does ...pharmacotherapy for cognitive symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for noncognitive symptoms improve outcomes in patients with dementia? 3) Do educational interventions improve outcomes in patients and/or caregivers? 4) Do other nonpharmacologic interventions improve outcomes in patients and/or caregivers?
Cholinesterase inhibitors benefit patients with AD (Standard), although the average benefit appears small; vitamin E likely delays the time to clinical worsening (Guideline); selegiline, other antioxidants, anti-inflammatories, and estrogen require further study. Antipsychotics are effective for agitation or psychosis in patients with dementia where environmental manipulation fails (Standard), and antidepressants are effective in depressed patients with dementia (Guideline). Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to nursing home placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline).
Validation of a simplified classification of mucosal morphology in prediction of histology in Barrett's esophagus using narrow-band imaging with magnification (NBI-Z) and assessing its ...reproducibility by endoscopists experienced in the use of NBI (NBI-experts) and by endoscopists who were new to NBI (non-NBI-experts).
In a prospective cohort study of 109 patients with Barrett's esophagus at a single tertiary referral center, mucosal patterns visualized in Barrett's esophagus on NBI-Z were classified into four easily distinguishable types: A, round pits with regular microvasculature; B, villous/ridge pits with regular microvasculature; C, absent pits with regular microvasculature; D, distorted pits with irregular microvasculature. The NBI-Z grading was compared with the final histopathological diagnosis, and positive (PPV) and negative predictive values (NPV) were calculated. The reproducibility of the grading was then assessed by NBI-expert and non-NBI-expert endoscopists, and interobserver and intraobserver agreement were calculated using kappa statistics.
Per-biopsy analysis: In 903 out of 1021 distinct areas (87.9%) the NBI-Z grading corresponded to the histological diagnosis. Per-patient analysis: The PPV and NPV for type A pattern (columnar mucosa without intestinal metaplasia) were 100% and 97% respectively; for types B and C (intestinal metaplasia) they were 88% and 91% respectively, and for type D (high-grade dysplasia) 81% and 99% respectively. Inter- and intraobserver agreement: The mean kappa values in assessing the various patterns were 0.71 and 0.87 in the non-expert group; 0.78 and 0.91 in the expert group.
This study has validated a simplified classification of the various morphologic patterns visualized in Barrett's esophagus and confirmed its reproducibility when used by NBI-expert and non-NBI-expert endoscopists.
Carbon (C) saturation theory suggests that soils have a limited capacity to stabilize organic C and that this capacity may be regulated by intrinsic soil properties such as clay concentration and ...mineralogy. While C saturation theory has advanced our ability to predict soil C stabilization, few biogeochemical ecosystem models have incorporated C saturation mechanisms. In biogeochemical models, C and nitrogen (N) cycling are tightly coupled, with C decomposition and respiration driving N mineralization. Thus, changing model structures from non-saturation to C saturation dynamics can change simulated N dynamics. In this study, we used C saturation models from the literature and of our own design to compare how different methods of modeling C saturation affected simulated N mineralization dynamics. Specifically, we tested (i) how modeling C saturation by regulating either the transfer efficiency (ε, g C retained g−1 C respired) or transfer rate (k) of C to stabilized pools affected N mineralization dynamics, (ii) how inclusion of an explicit microbial pool through which C and N must pass affected N mineralization dynamics, and (iii) whether using ε to implement C saturation in a model results in soil texture controls on N mineralization that are similar to those currently included in widely used non-saturating C and N models. Models were parameterized so that they rendered the same C balance. We found that when C saturation is modeled using ε, the critical C : N ratio for N mineralization from decomposing plant residues (rcr) increases as C saturation of a soil increases. When C saturation is modeled using k, however, rcr is not affected by the C saturation of a soil. Inclusion of an explicit microbial pool in the model structure was necessary to capture short-term N immobilization–mineralization turnover dynamics during decomposition of low N residues. Finally, modeling C saturation by regulating ε led to similar soil texture controls on N mineralization as a widely used non-saturating model, suggesting that C saturation may be a fundamental mechanism that can explain N mineralization patterns across soil texture gradients. These findings indicate that a coupled C and N model that includes saturation can (1) represent short-term N mineralization by including a microbial pool and (2) express the effects of texture on N turnover as an emergent property.
Land-use change is an important driver of soil-atmosphere gas exchange, but current greenhouse-gas budgets lack data from urban lands. Field comparisons of urban and non-urban ecosystems are required ...to predict the consequences of global urban-land expansion for greenhouse-gas budgets. In a rapidly urbanizing region of the U.S. Great Plains, we measured soil-atmosphere exchange of methane (CH4) and nitrous oxide (N2O) for one year in replicated (n = 3) urban lawn, native shortgrass steppe, dryland wheat-fallow, and flood-irrigated corn ecosystems. All soils were net sinks for atmospheric CH4, but uptake by urban, corn, and wheat-fallow soils was half that of native grasslands ($-0.30 \pm 0.04 g C\cdot m^{-2}\cdot yr^{-1}$mean ± 1 SE). Urban ($0.24 \pm 0.03 g N\cdot m^{-2}\cdot yr^{-1}$) and corn ($0.20 \pm 0.02 g N\cdot m^{-2}\cdot yr^{-1}$) soils emitted 10 times more N2O to the atmosphere than native grassland and wheat-fallow soils. Using remotely sensed land-cover data we calculated an upper bound for the contribution of lawns to regional soil-atmosphere gas fluxes. Urban lawns occupied 6.4% of a$1578-km^2$study region, but contribute up to 5% and 30% of the regional soil CH4consumption and N2O emission, respectively, from land-use types that we sampled. Lawns that cover small portions of the landscape may contribute significantly to regional soil-atmosphere gas exchange.
Ponderosa pine (Pinus ponderosa) forests of the southwestern United States are a mosaic of stands where undisturbed forests are carbon sinks, and stands recovering from wildfires may be sources of ...carbon to the atmosphere for decades after the fire. However, the relative magnitude of these sinks and sources has never been directly measured in this region, limiting our understanding of the role of fire in regional and US carbon budgets. We used the eddy covariance technique to measure the CO2 exchange of two forest sites, one burned by fire in 1996, and an unburned forest. The fire was a high‐intensity stand‐replacing burn that killed all trees. Ten years after the fire, the burned site was still a source of CO2 to the atmosphere 109±6 (SEM) g C m−2 yr−1, whereas the unburned site was a sink (−164±23 g C m−2 yr−1). The fire reduced total carbon storage and shifted ecosystem carbon allocation from the forest floor and living biomass to necromass. Annual ecosystem respiration was lower at the burned site (480±5 g C m−2 yr−1) than at the unburned site (710±54 g C m−2 yr−1), but the difference in gross primary production was even larger (372±13 g C m−2 yr−1 at the burned site and 858±37 g C m−2 yr−1at the unburned site). Water availability controlled carbon flux in the warm season at both sites, and the burned site was a source of carbon in all months, even during the summer, when wet and warm conditions favored respiration more than photosynthesis. Our study shows that carbon losses following stand‐replacing fires in ponderosa pine forests can persist for decades due to slow recovery of the gross primary production. Because fire exclusion is becoming increasingly difficult in dry western forests, a large US forest carbon sink could shift to a decadal‐scale carbon source.
The effects of sorafenib--an oral multikinase inhibitor targeting the tumour and tumour vasculature--were evaluated in patients with advanced melanoma enrolled in a large multidisease Phase II ...randomised discontinuation trial (RDT). Enrolled patients received a 12-week run-in of sorafenib 400 mg twice daily (b.i.d.). Patients with changes in bi-dimensional tumour measurements <25% from baseline were then randomised to sorafenib or placebo for a further 12 weeks (ie to week 24). Patients with > or =25% tumour shrinkage after the run-in continued on open-label sorafenib, whereas those with > or =25% tumour growth discontinued treatment. This analysis focussed on secondary RDT end points: changes in bi-dimensional tumour measurements from baseline after 12 weeks and overall tumour responses (WHO criteria) at week 24, progression-free survival (PFS), safety and biomarkers (BRAF, KRAS and NRAS mutational status). Of 37 melanoma patients treated during the run-in phase, 34 were evaluable for response: one had > or =25% tumour shrinkage and remained on open-label sorafenib; six (16%) had <25% tumour growth and were randomised (placebo, n=3; sorafenib, n=3); and 27 had > or =25% tumour growth and discontinued. All three randomised sorafenib patients progressed by week 24; one remained on sorafenib for symptomatic relief. All three placebo patients progressed by week-24 and were re-started on sorafenib; one experienced disease re-stabilisation. Overall, the confirmed best responses for each of the 37 melanoma patients who received sorafenib were 19% stable disease (SD) (ie n=1 open-label; n=6 randomised), 62% (n=23) progressive disease (PD) and 19% (n=7) unevaluable. The overall median PFS was 11 weeks. The six randomised patients with SD had overall PFS values ranging from 16 to 34 weeks. The most common drug-related adverse events were dermatological (eg rash/desquamation, 51%; hand-foot skin reaction, 35%). There was no relationship between V600E BRAF status and disease stability. DNA was extracted from the biopsies of 17/22 patients. Six had V600E-positive tumours (n=4 had PD; n=1 had SD; n=1 unevaluable for response), and 11 had tumours containing wild-type BRAF (n=9 PD; n=1 SD; n=1 unevaluable for response). In conclusion, sorafenib is well tolerated but has little or no antitumour activity in advanced melanoma patients as a single agent at the dose evaluated (400 mg b.i.d.). Ongoing trials in advanced melanoma are evaluating sorafenib combination therapies.
Forest soils are important components of the global carbon cycle because they both store and release carbon. Carbon dioxide is released from soil to the atmosphere as a result of plant root and ...microbial respiration. Additionally, soils in dry forests are often sinks of methane from the atmosphere. Both carbon dioxide and methane are greenhouse gases whose increasing concentration in the atmosphere contributes to climate warming. Thinning treatments are being implemented in ponderosa pine forests across the southwestern United States to restore historic forest structure and reduce the risk of severe wildfire. This study addresses how thinning alters fluxes of carbon dioxide and methane in ponderosa pine forest soils within one year of management and examines mechanisms of change. Carbon dioxide and methane fluxes, soil temperature, soil water content, forest floor mass, root mass, understory plant biomass, and soil microbial biomass carbon were measured before and after the implementation of a thinning and in an unthinned forest. Carbon dioxide efflux from soil decreased as a result of thinning in two of three summer months. Average summer carbon dioxide efflux declined by an average of 34
mg
C
m
−2
hr
−1 in the first year after thinning. Methane oxidation did not change in response to thinning. Thinning had no significant short-term effect on total forest floor mass, total root biomass, or microbial biomass carbon in the mineral soil. Understory plant biomass increased after thinning. Thinning increased carbon available for decomposition by killing tree roots, but our results suggest that thinning reduced carbon dioxide emissions from the soil because the reduction in belowground autotrophic respiration was larger than the stimulation of heterotrophic respiration. Methane oxidation was probably not affected by thinning because thinning did not alter the forest floor mass enough to affect methane diffusion from the atmosphere into the soil.
Ecosystem climate manipulation experiments (ECMEs) are a key tool for predicting the effects of climate change on ecosystems. However, the strength of inferences drawn from these experiments depends ...on whether the manipulated conditions mimic future climate changes. While ECMEs have examined mean temperature and moisture conditions, ecosystem processes may respond more to microclimatic thresholds (e.g., freeze–thaw events). We reported the mean and microclimatic thresholds from a post-clearcut ECME in a temperate, mixed deciduous forest. Target treatments were ambient, warmed (+∼2 °C), wetted (+∼20 % precipitation), and warmed + wetted. Wetted treatments increased mean monthly precipitation by 23 %, but did not change the amount of time the soil water potential was below the permanent wilting point. Relative to ambient, warmed treatments increased the mean temperatures of the surface and soil by 1.8 and 2.5 °C, respectively. Warming decreased the number of soil freeze–thaw events and increased the number of growing degree days, frost-free days, and amount of time leaf surface temperatures were in the optimal photosynthetic range. Our results showed that, even when ECMEs mimic mean predicted climate conditions, their effect on microclimatic thresholds can be variable. We suggest that measuring these and other microclimatic thresholds will be essential for interpreting ECME results and assessing their value in predicting ecosystem responses to future climate change.
High current pulsed-power generators efficiently store and deliver magnetic energy to z-pinch targets. We review applications of magnetically driven implosions (MDIs) to inertial confinement fusion. ...Previous research on MDIs of wire-array z-pinches for radiation-driven indirect-drive target designs is summarized. Indirect-drive designs are compared with new targets that are imploded by direct application of magnetic pressure produced by the pulsed-power current pulse. We describe target design elements such as larger absorbed energy, magnetized and pre-heated fuel, and cryogenic fuel layers that may relax fusion requirements. These elements are embodied in the magnetized liner inertial fusion (MagLIF) concept Slutz "Pulsed-power-driven cylindrical liner implosions of laser pre-heated fuel magnetized with an axial field," Phys. Plasmas, 17, 056303 (2010), and Stephen A. Slutz and Roger A. Vesey, "High-Gain Magnetized Inertial Fusion," Phys. Rev. Lett., 108, 025003 (2012). MagLIF is in the class of magneto-inertial fusion targets. In MagLIF, the large drive currents produce an azimuthal magnetic field that compresses cylindrical liners containing pre-heated and axially pre-magnetized fusion fuel. Scientific breakeven may be achievable on the Z facility with this concept. Simulations of MagLIF with deuterium-tritium fuel indicate that the fusion energy yield can exceed the energy invested in heating the fuel at a peak drive current of about 27 MA. Scientific breakeven does not require alpha particle self-heating and is therefore not equivalent to ignition. Capabilities to perform these experiments will be developed on Z starting in 2013. These simulations and predictions must be validated against a series of experiments over the next five years. Near-term experiments are planned at drive currents of 16 MA with D 2 fuel. MagLIF increases the efficiency of coupling energy (=target absorbed energy/driver stored energy) to targets by 10-150 X relative to indirect-drive targets. MagLIF also increases the absolute energy absorbed by the target by 10-50 X relative to indirect-drive targets. These increases could lead to higher fusion gains and yields. Single-shot high yields are of great utility to national security missions. Higher efficiency and higher gains may also translate into more compelling (lower cost and complexity) fusion reactor designs. We will discuss the broad goals of the emerging research on the MagLIF concept and identify some of the challenges. We will also summarize advances in pulsed-power technology and pulsed-power driver architectures that double the efficiency of the driver.
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