When an optical field is reflected from a compliant mirror, its intensity and phase become quantum-correlated due to radiation pressure. These correlations form a valuable resource: the mirror may be ...viewed as an effective Kerr medium generating squeezed states of light, or the correlations may be used to erase backaction from an interferometric measurement of the mirror’s position. To date, optomechanical quantum correlations have been observed in only a handful of cryogenic experiments, owing to the challenge of distilling them from thermomechanical noise. Accessing them at room temperature, however, would significantly extend their practical impact, with applications ranging from gravitational wave detection to chip-scale accelerometry. Here, we observe broadband quantum correlations developed in an optical field due to its interaction with a room-temperature nanomechanical oscillator, taking advantage of its high-cooperativity near-field coupling to an optical microcavity. The correlations manifest as a reduction in the fluctuations of a rotated quadrature of the field, in a frequency window spanning more than an octave below mechanical resonance. This is due to coherent cancellation of the two sources of quantum noise contaminating the measured quadrature—backaction and imprecision. Supplanting the backaction force with an off-resonant test force, we demonstrate the working principle behind a quantum-enhanced “variational” force measurement.
Quantum correlations between imprecision and backaction are a hallmark of continuous linear measurements. Here, we study how measurement-based feedback can be used to improve the visibility of ...quantum correlations due to the interaction of a laser field with a nanomechanical oscillator. Backaction imparted by the meter laser, due to radiation-pressure quantum fluctuations, gives rise to correlations between its phase and amplitude quadratures. These quantum correlations are observed in the experiment both as squeezing of the meter field fluctuations below the vacuum level in a homodyne measurement and as sideband asymmetry in a heterodyne measurement, demonstrating the common origin of both phenomena. We show that quantum feedback, i.e., feedback that suppresses measurement backaction, can be used to increase the visibility of the sideband asymmetry ratio. In contrast, by operating the feedback loop in the regime of noise squashing, where the in-loop photocurrent variance is reduced below the vacuum level, the visibility of the sideband asymmetry is reduced. This is due to backaction arising from vacuum noise in the homodyne detector. These experiments demonstrate the possibility, as well as the fundamental limits, of measurement-based feedback as a tool to manipulate quantum correlations.
This contribution presents the state of the art of economy-wide material flow accounting. Starting from a brief recollection of the intellectual and policy history of this approach, we outline system ...definition, key methodological assumptions, and derived indicators. The next section makes an effort to establish data reliability and uncertainty for a number of existing multinational (European and global) material flow accounting (MFA) data compilations and discusses sources of inconsistencies and variations for some indicators and trends. The results show that the methodology has reached a certain maturity: Coefficients of variation between databases lie in the range of 10% to 20%, and correlations between databases across countries amount to an average R2 of 0.95. After discussing some of the research frontiers for further methodological development, we conclude that the material flow accounting framework and the data generated have reached a maturity that warrants material flow indicators to complement traditional economic and demographic information in providing a sound basis for discussing national and international policies for sustainable resource use.
Summary
This contribution presents the state of the art of economy‐wide material flow accounting. Starting from a brief recollection of the intellectual and policy history of this approach, we ...outline system definition, key methodological assumptions, and derived indicators. The next section makes an effort to establish data reliability and uncertainty for a number of existing multinational (European and global) material flow accounting (MFA) data compilations and discusses sources of inconsistencies and variations for some indicators and trends. The results show that the methodology has reached a certain maturity: Coefficients of variation between databases lie in the range of 10% to 20%, and correlations between databases across countries amount to an average R2 of 0.95. After discussing some of the research frontiers for further methodological development, we conclude that the material flow accounting framework and the data generated have reached a maturity that warrants material flow indicators to complement traditional economic and demographic information in providing a sound basis for discussing national and international policies for sustainable resource use.
Aims
Bioequivalence (BE) trials aim to demonstrate that the 90% confidence interval of the T/R‐ratio of the pharmacokinetic metrics between two formulations (test T and reference R) of a drug is ...fully included in the acceptance interval 0.80, 1.25. Traditionally, the sample size of BE trials is based on a power calculation based on the intrasubject variability coefficient of variation (CV) and the T/R‐ratio of the metrics. Since the exact value of the T/R‐ratio is not known prior to the trial, it is often assumed that the difference between the treatments does not exceed 5%. Hence, uncertainty about the T/R‐ratio is expressed by using a fixed value for the sample size calculation. We propose to characterise the uncertainty about the T/R‐ratio by a (normal) distribution for the log(T/R‐ratio), with an assumed mean of log θ = 0.00 (i.e. θ = 1.00) and a standard deviation σu, which quantifies the uncertainty. Evaluating this distribution leads to the statistical assurance of the BE trial.
Methods
The assurance of a clinical trial can be derived by integrating the power over the distribution of the input parameters, in this case, the assumed distribution of the log(T/R)‐ratio. Because it is an average power, the assurance can be interpreted as a measure of the probability of success that does not depend on a specific assumed value for the log(T/R)‐ratio. The relationship between power and assurance will be analysed by comparing the numerical outcomes.
Results
Using the assurance concept, values of the standard deviation for the distribution of potential log(T/R)‐ratios can be chosen to reflect the magnitude of uncertainty. For most practical cases (i.e. when 0.95 ≤ θ ≤ 1.05), the sample size is not, or only slightly, changed when σ = |log(θ)|.
Conclusion
The advantage of deriving the assurance for BE trials is that uncertainty is directly expressed as a parameter of variability.
Introduction
Currently, no universally accepted definition of extended half‐life (EHL) recombinant FVIII (rFVIII) exists. Identifying the minimum half‐life extension ratio required for a reduction in ...dosing frequency compared with standard rFVIII could enable a more practical approach to decisions around prophylaxis with EHL rFVIII.
Aim
To identify the half‐life extension ratio required to decrease rFVIII dosing frequency by at least 1 day while maintaining the proportion of patients with plasma rFVIII levels above 1 IU/dL and without increasing the total weekly dose.
Methods
A previously published population pharmacokinetic model for standard rFVIII was used to estimate the percentage of patients with factor VIII (FVIII) levels always >1 IU/dL using various benchmark regimens. Using modelling, dosing frequency was reduced while rFVIII half‐life was extended until the percentage of patients with FVIII >1 IU/dL equalled that of the benchmark regimen.
Results
Benchmark 3×/wk dosing totalling 100 IU/kg/wk of rFVIII resulted in 56.6% of patients with FVIII levels always >1 IU/dL. With 2×/wk dosing, totalling 80 or 90 IU/kg/wk, half‐life extensions required to maintain 56.6% of patients at FVIII levels >1 IU/dL were 1.30 and 1.26, respectively. A half‐life extension ratio of 1.33 was required to change dosing from every 48 hours to every 72 hours (both at 105 IU/kg/wk) while maintaining 92.8% of patients with FVIII >1 IU/dL.
Conclusion
Based on this investigation, EHL rFVIII products should have a minimum half‐life extension ratio of 1.3 to provide a reduction in dosing frequency from 3× to 2×/wk compared with standard rFVIII products while maintaining the same minimum FVIII trough level.
We resolve the thermal motion of a high-stress silicon nitride nanobeam at frequencies far below its fundamental flexural resonance (3.4 MHz) using cavity-enhanced optical interferometry. Over two ...decades, the displacement spectrum is well-modeled by that of a damped harmonic oscillator driven by a 1/f thermal force, suggesting that the loss angle of the beam material is frequency-independent. The inferred loss angle at 3.4 MHz, ϕ=4.5⋅10−6, agrees well with the quality factor (Q) of the fundamental beam mode (ϕ=Q−1). In conjunction with Q measurements made on higher order flexural modes, and accounting for the mode dependence of stress-induced loss dilution, we find that the intrinsic (undiluted) loss angle of the beam changes by less than a factor of 2 between 50 kHz and 50 MHz. We discuss the impact of such “structural damping” on experiments in quantum optomechanics, in which the thermal force acting on a mechanical oscillator coupled to an optical cavity is overwhelmed by radiation pressure shot noise. As an illustration, we show that structural damping reduces the bandwidth of ponderomotive squeezing.
•Thermal motion of a high-Q SiN nanobeam is recorded far below its first resonance.•This motion is found to be 10–20 dB larger than conventional viscous damping models.•The excess noise is consistent with a frequency-independent intrinsic loss angle.•Structural damping is shown to limit quantum optomechanical effects likes squeezing.
The
f
2
test is generally used for comparing dissolution profiles. In cases of high variability, the
f
2
test is not applicable, and the Multivariate Statistical Distance (MSD) test is frequently ...proposed as an alternative by the FDA and EMA. The guidelines provide only general recommendations. MSD tests can be performed either on raw data with or without time as a variable or on parameters of models. In addition, data can be limited—as in the case of the
f
2
test—to dissolutions of up to 85% or to all available data. In the context of the present paper, the recommended calculation included all raw dissolution data up to the first point greater than 85% as a variable—without the various times as parameters. The proposed MSD overcomes several drawbacks found in other methods.
This book discusses research on the culture of postwar Germany (1945-1962). Topics such as war, destruction, homecoming, flight, expulsion, guilt, daily life, andreligion are explored systematically, ...using examples and by focusing on fiction, nonfiction, and film in the two German states.
Regional specifics reveal in differences in economic activity and structure, the institutional, socio-economic and cultural environment and not least in the capability of regions to create new ...knowledge and to generate innovations. Focusing on the regional level, this paper for three Australian territories (New South Wales, Victoria and Queensland) explores patterns of innovative activities in their private business sectors. Furthermore, these patterns are compared to specifics of each region's economic structure. We make use of input-output-based innovation flow networks, which are directed and weighted instead of binary. The value added of the proposed analysis is that we are able to trace a variety of different aspects related to the structure of innovative activities for each territory. It gets evident that mostly innovative activities in each territory are not strong in 'niche' branches but in fields of intense economic activity, signalising the high path-dependency of innovative activities in a specific geographical environment.
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