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Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages.
Methods
A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC–MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups.
Results
A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL.
Conclusions
The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.
Edited by
Nevena V. Radonjić, State University of New York Upstate Medical University,Thomas L. Schwartz, State University of New York Upstate Medical University,Stephen M. Stahl, University of California, San Diego
In this paper we extend results on reconstruction of probabilistic supports of independent and identically distributed random variables to supports of dependent stationary ${\mathbb R}^d$-valued random variables. All supports are assumed to be compact of positive reach in Euclidean space. Our main results involve the study of the convergence in the Hausdorff sense of a cloud of stationary dependent random vectors to their common support. A novel topological reconstruction result is stated, and a number of illustrative examples are presented. The example of the Möbius Markov chain on the circle is treated at the end with simulations.
In our last session of new material, we focus on body sensations that are soothing and pleasant. Practicing ways to lower our heart rate has been a part of every session and thus, by the time Session 9 occurs, children are very good at noticing and embracing calm, soothing sensations, This session is about rejoicing in moments of slow-moving wonderment – drifting off into a daydream, feeling the warmth of a smile, feeling alert as your senses take in everything around you. Children practice noticing everything surrounding them when they just stop and take in the moment. They see where their mind travels to when they find a restful spot to day dream. They feel time slipping away as they become engrossed in something that really focuses their attention. Catching and holding onto soothing moments is a wonderful way to live.
It is proven that a conjecture of Tao (2010) holds true for log-concave random variables on the integers: For every $n \geq 1$, if $X_1,\ldots,X_n$ are i.i.d. integer-valued, log-concave random variables, then
as $H(X_1) \to \infty$, where $H(X_1)$ denotes the (discrete) Shannon entropy. The problem is reduced to the continuous setting by showing that if $U_1,\ldots,U_n$ are independent continuous uniforms on $(0,1)$, then
In this chapter, we look first at the diameter of random graphs, i.e., the extreme value of the shortest distance between a pair of vertices. Then we look at the size of the largest independent set and the related value of the chromatic number. One interesting feature of these parameters is that they are often highly concentrated.
Chapter 21 discusses how children and young people with difficulties with attention and activity levels can best be supported. We also discuss how the diagnoses of attention deficit and hyperactivity disorder (ADHD) and attention deficit disorder (ADD) are made and how these conditions can be treated. We examine both behaviour and medication strategies and support at school and at home.
Concentration is the final stage of the noble eightfold path but is followed by insight and liberation in the tenfold series. It is usually described as achieved through practice of a series of four ever deeper states of mental one-pointedness known as jhānas. This series is often extended to five in later texts and may be followed by a second series of so-called “formless states” culminating in complete “cessation”. This chapter identifies key discrepancies between the fourfold and fivefold series, focussing particularly on the description of first jhāna and how this should be understood. The discussion critically examines the conclusions of other Buddhist scholars as to how differing accounts are likely to have arisen. It concludes that concentration as understood in early Buddhism originally consisted only of the set of four jhānas and that the sequence of “formless states” is therefore almost certainly a late doctrinal addition.
Buddhist origins and discussion of the Buddha’s teachings are amongst the most controversial and contested areas in the field. This bold and authoritative book tackles head-on some of the key questions regarding early Buddhism and its primary canon of precepts. Noting that the earliest texts in Pali, Sanskrit, and Chinese belong to different Buddhist schools, Roderick S. Bucknell addresses the development of these writings during the period of oral transmission between the Buddha’s death and their initial redaction in the first century bce. A meticulous comparative analysis reveals the likely original path of meditative practice applied and taught by Gotama. Fresh perspectives now emerge on both the Buddha himself and his enlightenment. Drawing on his own years of meditative experience as a Buddhist monk, the author offers here remarkable new interpretations of advanced practices of meditation, as well as of Buddhism itself. It is a landmark work in Buddhist studies.
Buddhist origins and discussion of the Buddha's teachings are amongst the most controversial and contested areas in the field. This bold and authoritative book tackles head-on some of the key questions regarding early Buddhism and its primary canon of precepts. Noting that the earliest texts in Pali, Sanskrit and Chinese belong to different Buddhist schools, Roderick S. Bucknell addresses the development of these writings during the period of oral transmission between the Buddha's death and their initial redaction in the first century BCE. A meticulous comparative analysis reveals the likely original path of meditative practice applied and taught by Gautama. Fresh perspectives now emerge on both the Buddha himself and his Enlightenment. Drawing on his own years of meditative experience as a Buddhist monk, the author offers here remarkable new interpretations of advanced practices of meditation, as well as of Buddhism itself. It is a landmark work in Buddhist Studies.
We study the social structure of ownership of German joint-stock firms covering the period 1869 to 1945 based on a random sample of attendance lists of general meetings. We confirm previous research findings based on smaller samples that despite several changes in the economic and political environment, the majority of shares of the attendees of the general meetings remained firmly in the hands of a few male and mostly inside investors. Moreover, we closely investigate the socio-economic characteristics of the shareholders. We do occasionally find investors from lower social classes and women, but their share of votes was negligible. Adding to the discussion of whether banks strongly monitored and controlled German industrial firms, we aim to track their impact at the meetings. In about 30 per cent of the meetings, a banker or bank was the most influential shareholder and in more than 50 per cent of the meetings a banker or bank was among the three largest shareholders, remarkably without necessarily owning the shares themselves. Although we cannot evaluate whether the banks used this power to pursue their targets, they certainly were in a position to do so.
We present in this chapter the empirical techniques used to measure market efficiency and its implications, starting with the so-called OP gap and its dynamic version. We will then discuss the Foster productivity decomposition method and the Hsieh and Klenow techniques to measure allocative inefficiency. Market inefficiency is also related to concentration and market power. When competition in a market is reduced, aggregate productivity growth may decrease, reducing consumer welfare.
For empirical measures supported on a random sample, statistical bounds describe the large-sample asymptotic behavior of the empirical Christoffel function. The Christoffel function associated with a fixed degree will converge to its population counterpart in the large-sample limit. The convergence can be made quantitative using random matrix concentration. Furthermore, in the context of singularly supported population measure, the rank will stabilize almost surely for a finite number of samples.
To explore whether embryo culture with melatonin (MT) can improve the embryonic development and clinical outcome of patients with repeated cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure, immature oocytes from controlled ovarian superovulation cycles were collected for in vitro maturation (IVM) and ICSI. The obtained embryos were cultured in 0, 10–11, 10–9, 10–7 and 10–5 M MT medium respectively, and 10–9 M was screened out as the optimal concentration. Subsequently, 140 patients who underwent failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with a medium containing 10–9 M MT, these 140 MT culture cycles were designated as the experimental group (10–9 M group), and the control group was the previous failed cycles of patients (0 M group). The results showed that the fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10–9 M group were significantly higher than those of the 0 M group (P < 0.01; P < 0.01; P < 0.0001; P < 0.0001; P < 0.0001). To date, in total, 50 vitrified-warmed cycle transfers have been performed in the 10–9 M group and the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher than those in the 0 M group (all P < 0.0001). Two healthy infants were delivered successfully and the other 18 women who achieved clinical pregnancy also had good examination indexes. Therefore the application of 10–9 M MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and had good clinical outcomes.
This topic relates to capital budgeting. The starting point is an explanation of why investment analysis is important in managerial economics, and the different types of investment and investment decision. Cash flow analysis and the principles involved in identifying and measuring relevant cash flows is discussed. The concept of risk and types of risk, stand-alone risk, within-firm risk and market risk, are discussed. The security market line (SML), beta coefficients and the capital asset pricing model (CAPM) are explained. The cost of capital is examined, explaining the calculation of the cost of debt, the cost of equity and the weighted average cost of capital (WACC). Methods of evaluation of individual projects are discussed, with a focus on net present value (NPV) and internal rate of return (IRR). There is a discussion of the determination of the optimal capital budget for a firm, in terms of the investment opportunity schedule (IOS) and the marginal cost of capital (MCC), with the distinction between mutually exclusive projects and independent projects. Case studies include two resource-heavy situations: the HS2 rail link and 5G telecommunications.
This topic examines government policy and regulation. The starting point is the objectives of government regulation and market failure. The implications for managerial decision making are outlined. The nature of market failure and its different aspects are discussed. Externalities are discussed, and the policy implications. Public goods, and their nature and policy implications, are examined. Imperfect information and the policy implications are discussed. Transaction costs are discussed. Monopoly and the nature of market power and its consequences are examined. Strategic behaviour, such as collusion, predatory pricing and exclusive dealing, is discussed. The distinction between structural and strategic barriers to entry and their different policy implications is explained. Aspects of new technology are discussed, such as network effects and the ‘winner-takes-most’ phenomenon. Various policy approaches and their costs and benefits are examined. Case studies involve two situations in the UK where governments may have made errors of policy. A final case study relates to the global phenomenon of increasing concentration and its consequences.
This chapter provides an assessment of the economic merits of the New Competition Tool (NCT), as it was considered by the European Commission as a tool to address structural competition problems in a timely and effective manner. The NCT has strong analogies to the UK’s “markets regime,” which empowers the UK competition regulator, the Competition and Markets Authority (CMA), to initiate market studies and investigations. The authors review the UK’s markets regime and survey some of the competition concerns the regime is intended to address. This includes a selective review of UK market studies and investigations to illustrate some of the ways these concerns have been explored and a description of the remedies imposed or proposed. The authors conclude with a critical evaluation of the UK’s markets regime in light of this evidence and offer seven recommendations regarding the merits and design of market investigations as a New Competition Tool for the EU. In sum, they see a strong case for the introduction of a New Competition Tool to address factors that prevent effective competition in markets, and they see no benefit to limiting it to specific sectors and to dominant firms.
We argue that concentration of power in religious hospitals threatens disestablishment values. When hospitals deny care for religious reasons, they dominate patients’ bodies and convictions. Health law should — and to some extent already does — constrain such religious domination.
In this Research Communication we focus the food industry´s broad tendency to decrease sugar content in food products onto dulce de leche (DL) and examine the influence of sucrose reduction on the detrimental deposits formed during the production process. The method used to identify the impact produced directly on the heat exchanger during the production of this product with low sucrose content required varying the quantity of sucrose in the milk. Different percentages of sucrose (20, 15, 10, 5 and 0% w/w) were submitted to the DL concentration process in a process simulator. After concentration, the quantification of the deposits formed in each was carried out and these deposits were characterized according to their composition. Methods such as Kjeldahl, Pregl-Dumas and sem-EDS were used. Thus, the work highlights the need to change the product manufacturing process due to changes in the formulation that directly impact the formation of deposits in the equipment used (fouling). This deposit changes significantly in relation to its quantity as well as in relation to the composition and chemical characteristics as the gradual reduction of the sucrose content in the production takes place. Therefore, these impacts must be considered in order to maintain better manufacturing and ensure efficient cleaning of equipment.
Regulation is not adjusting fast enough to changes in market structure due to unanticipated changes in technology and preferences. Regulators need to conduct diagnostics to assess the impact of abuse of market power, both ex ante (e.g. in the context of mergers) and ex post (e.g. in gauging profit margins). Both the empirical and the more conceptual assessments of the tools available to conduct these diagnostics are misleading if the market details are underestimated and/or the necessary accounting data are only partially available. The regulation of a vertically integrated monopoly participating in a competitive market in some of its production activities can lead to multiple benefits and risks. Benefits include the efficiency payoffs of the competition effect, the optimization of production cost synergies, and the incentive to innovate to remain competitive. Risks include a higher uncertainty on quality, social and political outcomes, and on the enforcement of access rules and prices. Whether the access prices should be based on the global price cap or the efficient component pricing rule approach is still up for debate. For two-sided markets, the regulator needs to account for the difference in valuation of the same service on the two sides of the market, interactions between the two sides, and the possible desirability of cross-subsidies to finance the common facility.