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Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales.
Design:
Retrospective anchor- and distribution-based analyses of change in apathy symptom scores.
Setting:
Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively.
Participants:
Two hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer’s disease.
Measurements:
The Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory – Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics.
Results:
Among the MCID was a decrease of four points (95% CI: −4.0 to −4.8) on the NPI-A, 0.56 points (95% CI: −0.47 to −0.65) on the DAIR, and three points on the AES-I (95% CI: −0.9 to −5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID.
Conclusions:
MCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales.
This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.
Methods:
A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.
Results:
Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).
Discussion:
Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.
Assessment of mass-produced animal-housing equipment can serve as a basis for improving animal welfare. A number of European countries have adopted various legal approaches to such assessment. In Germany, welfare assessment of housing equipment is voluntary, but minimum standards can be set by regulation for the assessment procedure and for the qualifications of the persons involved. From a scientific perspective, the time and resource constraints pose some problems, particularly as they apply to a voluntary procedure. For reasons of practicability, certain compromises will be required. Nevertheless, it is important to ensure that each assessment procedure is based upon scientific principles and considers animal welfare aspects to a sufficient extent. A proposal for the minimum standards of an assessment procedure has been elaborated by the Animal Welfare Committee of the German Agricultural Society (Deutsche Landwirtschafts-Gesellschaft, DLG), a shortened version of which is presented here. The animal welfare impact of such a regulated but voluntary procedure will be less than that of an obligatory assessment; however, the relatively flexible approach may still significantly contribute to the improvement of welfare aspects of livestock housing.
Driving in persons with dementia poses risks that must be counterbalanced with the importance of the care for autonomy and mobility. Physicians often find substantial challenges in the assessment and reporting of driving safety for persons with dementia. This paper describes a driving in dementia decision tool (DD-DT) developed to aid physicians in deciding when to report older drivers with either mild dementia or mild cognitive impairment to local transportation administrators.
Methods:
A multi-faceted, computerized decision support tool was developed, using a systematic literature and guideline review, expert opinion from an earlier Delphi study, as well as qualitative interviews and focus groups with physicians, caregivers of former drivers with dementia, and transportation administrators. The tool integrates inputs from the physician-user about the patient's clinical and driving history as well as cognitive findings, and it produces a recommendation for reporting to transportation administrators. This recommendation is translated into a customized reporting form for the transportation authority, if applicable, and additional resources are provided for the patient and caregiver.
Conclusions:
An innovative approach was needed to develop the DD-DT. The literature and guideline review confirmed the algorithm derived from the earlier Delphi study, and barriers identified in the qualitative research were incorporated into the design of the tool.
Field experiments were conducted in 2008 and 2010 to determine crop tolerance and weed control efficacy of the POST herbicides bentazon, flumioxazin, and oxyfluorfen applied to direct-seeded dry bulb onions on organic soil. Postemergence application of oxyfluorfen at 0.071 kg ai ha−1 resulted in less than 20% onion injury when applied at the 2 and 4 onion leaf stages and provided good control of ladysthumb and common lambsquarters. Oxyfluorfen EC caused slightly higher visual injury than oxyfluorfen SC, but there was no difference in onion yield among the treatments. Application of flumioxazin at 0.036 of 0.072 kg ai ha−1 alone or in combination with pendimethalin ACS resulted in minimal onion injury and no yield reduction. Combining flumioxazin in a tank mix with pendimethalin EC, dimethenamid-P EC, or S-metolachlor EC resulted in significant onion injury and yield reduction. Flumioxazin plus S-metolachlor, dimethenamid-P, or pendimethalin improved ladysthumb control in one of two years. Bentazon applied at 0.56 kg ai ha−1 produced moderate onion injury and did not control yellow nutsedge adequately. Bentazon applied at 1.12 kg ai ha−1 provided good control of yellow nutsedge but caused serious onion injury and yield loss.
The coast of Ceará State in NE Brazil is covered by vast fields of active and stabilized coastal sand dunes. Its tropical climate is characterized by two seasons, wet and dry, with wind intensity determined by the meridional shift of the Intertropical Convergence Zone. The wind power is negatively correlated with precipitation, and precipitation is negatively correlated with the difference between sea surface temperatures of the tropical Atlantic north and south of the equator. We present a model suggesting that during the Late Pleistocene wind power determined the mobility and stability of the dunes. Sand dunes accumulated during periods of high wind power (as it is today) and stabilized when wind power was low. Once the dunes were stabilized by vegetation they could not be activated even by increased wind power. Samples that were taken for luminescence dating from 25 stabilized dunes along the coasts of Ceará gave ages ranging from135 ka to < 100 yr. We postulate that these luminescence ages fall at the beginning of wet periods in NE Brazil characterized by low wind power. These paleoclimatic wet periods correlate well with the cold periods of stades in Greenland ice-core records.
Asymptotic expressions for the onset of convection in a horizontal fluid layer of finite extent heated from below and rotating about a vertical axis are derived in the limit of large rotation rates in the case of stress-free upper and lower boundaries. In the presence of vertical sidewalls, the critical Rayleigh number Rc is much lower than the classical value for an infinitely extended layer. In particular, we find that Rc grows in proportion to τ when the sidewall is insulating, where τ is the dimensionless rotation rate. When the sidewall is infinitely conducting, Rc grows in proportion to $\tau^{\frac{4}{3}}$ as in the case of an infinitely extended layer but with a lower coefficient of proportionality. Numerical results obtained at finite values of τ show good agreement with the asymptotic formulae.
Linear stability theory and bifurcation analysis are used to investigate the role of gravity in shear-band formation in granular Couette flow, considering a kinetic-theory rheological model. We show that the only possible state, at low shear rates, corresponds to a ‘plug’ near the bottom wall, in which the particles are densely packed and the shear rate is close to zero, and a uniformly sheared dilute region above it. The origin of such plugged states is shown to be tied to the spontaneous symmetry-breaking instabilities of the gravity-free uniform shear flow, leading to the formation of ordered bands of alternating dilute and dense regions in the transverse direction, via an infinite hierarchy of pitchfork bifurcations. Gravity plays the role of an ‘imperfection’, thus destroying the ‘perfect’ bifurcation structure of uniform shear. The present bifurcation problem admits universal unfolding of pitchfork bifurcations which subsequently leads to the formation of a sequence of a countably infinite number of ‘isolas’, with the solution structures being a modulated version of their gravity-free counterpart. While the solution with a plug near the bottom wall looks remarkably similar to the shear-banding phenomenon in dense slow granular Couette flows, a ‘floating’ plug near the top wall is also a solution of these equations at high shear rates. A two-dimensional linear stability analysis suggests that these floating plugged states are unstable to long-wave travelling disturbances.The unique solution having a bottom plug can also be unstable to long waves, but remains stable at sufficiently low shear rates. The implications and realizability of the present results are discussed in the light of shear-cell experiments under ‘microgravity’ conditions.
The dynamics of dry granular flows down a vertical glass pipe of small diameter have
been studied experimentally. Simultaneous measurements of pressure profiles, air and
grain flow rates and volume fractions of particles have been realized together with
spatio-temporal diagrams of the grain distribution down the tube. At large grain flow
rates, one observes a stationary flow characterized by high particle velocities, low
particle fractions and a downflow of air resulting in an underpressure in the upper
part of the pipe. A simple model assuming a free fall of the particles slowed down by
air friction and taking into account finite particle fraction effects through Richardson–Zaki's
law has been developed: it reproduces pressure and particle fraction variations
with distance and estimates friction forces with the wall. At lower flow rates, sequences
of high-density plugs separated by low-density bubbles moving down at a constant
velocity are observed. The pressure is larger than outside the tube and its gradient
reflects closely the weight of the grains. Writing mass and momentum conservation
equations for the air and for the grains allows one to estimate the wall friction, which
is less than 10% of the weight for grains with a clean smooth surface but up to
30% for grains with a rougher surface. At lower flow rates, oscillating-wave regimes
resulting in large pressure fluctuations are observed and their frequency is predicted.