Earlier Formulations Research Articles

Childhood attachment and schizophrenia: The “attachment-developmental-cognitive” (ADC) hypothesis

Schizophrenia is a complex psychiatric syndrome whose exact causes remain unclear. However, current scientific consensus has highlighted the importance of neurodevelopmental and neurocognitive processes in the development of schizophrenic symptoms. Research over the past three decades, motivated by the findings of the World Health Organization’s large-scale studies, has highlighted the importance of psychosocial adversities – including childhood abuse and neglect – in this disorder. In this paper, I propose a hypothesis based on John Bowlby’s framework of attachment theory, which I have termed the attachment-developmental-cognitive (ADC) hypothesis. The ADC hypothesis integrates recent developments related to (1) existing models of schizophrenia, (2) studies examining the effect of attachment on brain biology and cognitive development, and (3) various known facts about the course and outcome of this disorder. In doing so, it explains how disturbed childhood attachment leads to core psychological and neurochemical abnormalities which are implicated in the genesis of schizophrenia and also affect its outcome. The ADC hypothesis compasses and expands on earlier formulations, such as the “social defeat” and “traumagenic” models, and has important implications regarding the prevention and treatment of schizophrenia. Ways of testing and refining this hypothesis are outlined as avenues for future research. Though provisional, the ADC hypothesis is entirely consistent with both biological and psychosocial research into the origins of schizophrenia.

The Second Lie-Group $SO_o(n,1)$ Used to Solve Ordinary Differential Equations

Liu (2001) derived the first augmented Lie-group $SO_o(n,1)$ symmetry for the nonlinear ordinary differential equations (ODEs): $\dot{\bf x}={\bf f}({\bf x},t)$, and developed the corresponding group-preserving scheme (GPS). However, the earlier formulation did not consider the rotational effect of nonlinear ODEs. In this paper, we derive the second augmented Lie-group $SO_o(n,1)$ symmetry by taking the rotational effect into account. The numerical algorithm exhibits two solutions of the Lie-group ${\bf G} \in SO_o(n,1)$, depending on the sign of $\|{\bf f}\|^2 \|{\bf x}\|^2-2({\bf f}\cdot{\bf x})^2$, which means that the algorithm may be switched between two states, depending on ${\bf x}$. We give numerical examples to assess the new algorithm GPS2, which upon comparing with the GPS can raise the accuracy about three orders. It is interesting that for the chaotic system the signum function sign$(\|{\bf f}\|^2 \|{\bf x}\|^2-2({\bf f}\cdot{\bf x})^2)$ is frequently switched between $+1$ and $-1$ in time.

Connectionism coming of age: legacy and future challenges.

Connectionism coming of age: legacy and future challenges.

Dose Regimen of Para-Aminosalicylic Acid Gastro-Resistant Formulation (PAS-GR) in Multidrug-Resistant Tuberculosis

Resurgence of multidrug-resistant tuberculosis (MDR-TB) has raised a renewed interest in para-aminosalicylic acid (PAS) and other efficacious drugs. A gastro-resistant granule formulation (PAS-GR) was designed to be better tolerated than earlier forms of PAS, with fewer adverse effects from reduced production of meta-aminophenol. PAS release from PAS-GR granules is slower than with earlier formulations. Pharmacokinetic data are, however, limited and only a few studies have assisted in defining the best PAS-GR dose regimen. Interest in refining the latter continues and recent data contributed in better defining the optimal PAS-GR dose regimen in adults and children. The present paper draws on these recent studies, synthesizes pharmacokinetic results from different population groups, and draws comparisons with in vitro data and the results of earlier pharmacokinetic studies in order to discuss the most appropriate dosing regimen for PAS-GR. A comparative in vitro dissolution study was carried out with a 1 g acid PAS equivalent of various formulations of PAS and PAS-GR and in vitro-in vivo correlations. Retrospective comparisons between recent and earlier clinical studies were also gathered to clarify the dose regimen of PAS-GR in adults and children. Exposure after a 4 g twice- or three times daily dose regimen in adult MDR-TB patients confirmed that both dose regimens can be used. The twice-daily dose regimen does not, however, confer any safety margin over the potentiality of "too" high plasma concentrations after a three times daily dose regimen and may lead to under-dosage when a dose is missed, as compliance often decreases over time. Based on available data and practical considerations, a 4 g three times daily dose regimen of PAS-GR should be the preferred dose in hospital settings, where it remains the best regimen to cover the around-the-clock suppression of mycobacteria based on the minimal inhibitory concentration for PAS. In MDR-TB adults and in hospital settings, there is no safety advantage in administering a regimen of 4 g twice daily. As compliance is critical to the effectiveness of the treatment, a 4 g three times daily dose regimen may be more forgiving if the patient misses a dose.

P.11.14 Phase 1b single and multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics of HT-100 in DMD

In DMD, chronic inflammation leads to endomysial fibrosis, resulting in abnormal force transmission, decreased muscle perfusion and impairment of muscle regeneration. This pathology is directly related to progressive deterioration in motor, respiratory and cardiac function. Halofuginone hydrobromide is an orally-delivered anti-fibrotic and anti-inflammatory agent with effects on molecular, pathology, and functional phenotypes of dystrophic mice, making it a promising candidate for clinical development in DMD. Earlier formulations have been associated with tolerability issues at higher doses which limited the total daily dose that could be administered. Halo Therapeutics has developed HT-100, a delayed-release formulation, allowing for delivery of potentially larger doses with enhanced tolerability. This new formulation has undergone initial testing in animals (canines) where it was well tolerated and resulted in similar systemic exposure to the original formulation. While these results are encouraging, the tolerability and pharmacokinetics (PK) profile of the new formulation needs to be confirmed in the DMD patient population. The current trial is designed to provide initial safety, tolerability, and PK data in DMD participants with a broad spectrum of the disease in order to provide information regarding safety and tolerability and to inform dose selection for a future larger study to be conducted in a more homogenous DMD population. After completion of the Phase Ib ascending dose phase of this study, participants will be eligible to enroll in a 6-month, open-label extension study. Background and supporting data on HT-100 will be presented as well as the Phase Ib and extension study clinical protocols.

(Mis)reading Lonergan’s Way to Nicea

This article examines Jane Barter Moulaison’s critique of Bernard Lonergan’s The Way to Nicea, and proposes a more generous interpretation of his project. Barter Moulaison’s critique rests upon a misreading of Lonergan. She conceives of doctrine as a liturgical distillation of Christian narrative, but he understands the Nicene homoousion as a shift toward systematic meaning in the expression of Christian teaching. This shift presupposes a Christian realism mediated by true judgments. It developed through a dialectical process in which the inadequacies of earlier formulations were gradually brought to light and eliminated, to arrive at the judgment that what is true of the Father is equally true of the Son and the Holy Spirit.

Applying two efficient hybrid heuristics for hub location problem with fully interconnected backbone and access networks

This paper considers the design of two-layered networks with fully interconnected backbone and access networks. The problem, a specific application of hub location to network design, is known as fully interconnected network design problem (FINDP). A novel mathematical programming formulation advantageous over an earlier formulation is presented to model the problem. Two hybrid heuristics are proposed to solve the problem, namely SAVNS and TSVNS which incorporate a variable neighborhood search (VNS) algorithm into the framework of simulated annealing (SA) and tabu search (TS). The proposed algorithms are able to easily obtain the optimal solutions for 24 small instances existing in the literature in addition to efficiently solve new generated medium and large instances. Results indicate that the proposed algorithms generate high quality solutions in a quite short CPU time.

Should monitoring of vancomycin be delayed? A case of likely nephrotoxicity occasioned by morbid obesity and minimal monitoring

Should monitoring of vancomycin be delayed? A case of likely nephrotoxicity occasioned by morbid obesity and minimal monitoring

Firefly optimization to determine the precipitation field on South America

A model simulation of an intense rainfall associated with a case of South Atlantic Convergence Zone that occurred during 21–24 February 2004 using the Brazilian developments on the Regional Atmospheric Modelling System was performed. The convective parameterization scheme of Grell and Dévényi was used to represent clouds of the sub-grid scale and their interaction with the large-scale environment. This method is a convective parameterization that can make use of a large variety of approaches previously introduced in earlier formulations, considering an ensemble of several hypotheses and closures. The rainfall was evaluated by six experiments, using different choices of rainfall parameterizations, providing six different simulated responses for the rainfall field. The sixth experiment ran with an average among five closures (ensemble mean). The purpose of this study was to generate a set of weights to compute a best combination of the ensemble members. This inverse problem of parameter estimation is solved as an optimization problem. The objective function was computed with the quadratic difference between five simulated precipitation fields and observation. The precipitation field estimated by the Tropical Rainfall Measuring Mission satellite was used as observed data. Weights were obtained using the firefly optimization algorithm and it was included in the cumulus parameterization code to simulate precipitation. The results indicated the better skill of the model with the new methodology compared with the old ensemble mean calculation.

A constante experiência do self: aproximações conceituais entre Dewey e Mead

We look at our article on a relational communication approach. In this sense, we seek to understand the communication process from a praxeological model as elaborated by Louis Quere (1991), rather than an epistemological model, seized in earlier formulations about the communicative practice. With pragmatism as a guideline of our argument, we are interested in understand and approach the notions of self and experience as discussed by John Dewey (1896, 1980, 2010) and George Herbert Mead (1934). Both concepts seem appropriate to think about communication. Our purpose is then to see to what extent we can reasonably argue that the self is in constant experience and the implications that permeate this conceptual relationship.

What's Sincerity Got to Do with It? Freedom of Religion in Canada

Recently, the Supreme Court of Canada (SCC) returned to the test of individual sincerity for determining whether there has been an infringement of freedom of religion pursuant to section 2(a) of the Canadian Charter of Rights and Freedoms (the Charter) in SL c Commission scolaire des Chênes. Sincerity of belief or in practice as necessary for religious expression on the part of a complainant has been accepted from some of the earliest Charter cases as the triggering requirement for a section 2(a) claim, and, in itself, sufficient to establish a claim which a court must then balance against conflicting claims pursuant to section 1 (‘reasonable limits prescribed by law as can be demonstrably justified in a free and democratic society’) or section 15 (equality rights). In SL, the court confirmed that mere sincerity is no longer sufficient and that an objective burden of proof now rests on a claimant to show how a state-sanctioned requirement infringes the fundamental right to freedom of religion before competing claims will be assessed. In SL, the court found that the complainants had failed to show how a religious education course mandated for all students without exception by the Government of Quebec interfered with what they argued was their religious freedom as Roman Catholic parents to pass on their faith to their children. This result has also been interpreted to mean that the state has a right prior to parental rights in the religious formation of their own children, and, on this reading, has been highly controversial. The court's new formulation of a sincerity test may be of interest elsewhere. The earlier formulation in Syndicat Northcrest v Anselem was adopted by the House of Lords in R (Williamson) v Secretary of State for Education and Employment, and the subsequent spread of its use has since been subject to consideration in England.

RNAi Therapeutics: The Teenage Years

RNAi Therapeutics: The Teenage Years

Whither the Preconventional Child? Toward a Life‐Span Moral Development Theory

AbstractA vigorous research literature focused on early childhood conscience, prosocial behavior, and empathy—and also theory of mind, emotion understanding, and social cognition—has important implications for moral development theory. It offers a new understanding of the early conceptual, affective, and relational foundations of moral development. In addition, it provides the opportunity to create a genuinely life‐span theory of moral development when it is considered together with the research literatures on moral character, identity, and judgment at older ages. The purpose of this article is to summarize current research on the early foundations of moral development, highlighting how it compares with earlier formulations and describing its implications for constructing a life‐span moral development theory to guide future research.

An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest

Natural estrogens such as estradiol (E2) or its valerate ester (E2V) offer an alternative to ethinyl estradiol (EE). E2-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E2V-containing preparations have been approved to date for contraceptive use: E2V/cyproterone acetate (CPA) (Femilar®; only approved in Finland and only in women >40 years or women aged 35–40 years in whom a COC containing EE is not appropriate) and E2V/dienogest (DNG; Qlaira®/Natazia®). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E2V/DNG.

Battling about equations

One of the most exciting episodes in the study of human heredity was the battle between two incompatible algebraic expressions to describe its properties in the beginning of the 20th Century. In one corner was Karl Pearson (1857–1936) with his 1898 formulation for ancestral heredity, which had the authority of Charles Darwin and Francis Galton for support.1 It reads: The inherited contribution of parent to offspring (y) can be formulated as: ![Formula][1] where σ/σn are the ratios of the standard deviations of measurable traits in the offspring to the standard deviations of the mid-parental generation; and k1,k2 … kn are the deviations of the mid-parental means from the mean of the offspring for each trait. He admits to reservations of how ‘mid-parent’ should be defined. The subscripts refer to each of the ancestral generations (parents, grandparents, great-grandparents, etc.). The original paper should be consulted for fuller details.2 Pearson has elaborated on earlier formulations using a convergent geometric series to represent the hereditary contribution (f(y)) by the parents, the four grand parents, eight great-grand parents, etc. to the offspring.1 This type of convergent series is of the general form: ![Formula][2] where A,B,C,D … are constants independent of x (=0.5n in Pearson's expression). The expression can be used to represent a great many biological phenomena. The formulation has no theoretical significance; all it postulates is that the phenomenon in question varies continuously. Then Maclaurin's or Taylor's theorems (depending on the number of variables involved) can be used to determine the values of the coefficients that will make the series useful to any desired degree of approximation.3 Pearson's equation certainly satisfies the requirements for continuous variation of inherited traits which Darwin believed to be true; and it reaches a limit … [1]: /embed/graphic-1.gif [2]: /embed/graphic-2.gif

Instrumental errors in spectral-width turbulence measurements by radars

Measurements of turbulent energy dissipation rates by radar spectral-width procedures require differencing two numbers to produce a difference that is small relative to the two initial numbers. In particular, the square of the so-called “beam-broadening” component must be subtracted from the square of a measured spectral width. Because the difference is relatively small, it is very sensitive to statistical fluctuations in each of the initial measured parameters. The method by which the measured spectral width is determined can impact the accuracy of the measurements, and, in addition, the beam-broadened component is affected by errors in the measured wind, variability in the mean wind, wind-shear, and aspect-sensitivity of the scatterers. All these effects can impact the measurements of turbulence, and in some cases can even produce physically unrealistic “negative” values of turbulence strength. In this paper, we investigate the relative importance of (i) variability of the mean wind within the averaging period, (ii) digitization errors and the accuracy of determination of the spectral width, (iii) the particular beam-broadening model employed, and (iv) anisotropy of the scatterers. Although these terms are often discussed in the literature, we have quantified their relative importance. The accuracy of determination of the spectral width is the most important source of error, followed by variability of the mean wind in the averaging period. In addition to these studies, we also develop a new formula for accurate determination of the beam-broadened spectral width. This includes a new term that was missing from earlier formulations.

A Spectral Coupled-Mode Formulation for Sound Propagation around Axisymmetric Seamounts

A spectral coupled-mode solution of the three-dimensional (3D) acoustic field generated by a point source in the presence of an axisymmetric seamount is developed. Based on the same theoretical foundation as the formulation presented by Taroudakis [J. Comput. Acoust. 4 (1996) 101], the present approach combines a spectral decomposition in azimuth with a coupled-mode theory for two-way range-dependent propagation. However, the earlier formulations are severely limited in terms of frequency, size and geometry of the seamount, the seabed composition, and the distance between the source and the seamount, and are therefore severely limited in regard to realistic seamount problems. Without changing the fundamental theoretical foundation, the present approach applies a number of modifications to the formulation, leading to orders of magnitude improvement in numerical efficiency for realistic problems. Therefore, realistic propagation and scattering scenarios can be modeled, including effects of seamount roughness and realistic sedimentary structure.

The Uniform Probate Code’s Elective Share: Time for a Reassessment (With an Addendum Reporting on Post-Publication Amendments)

This Article reproduces in a slightly revised format an Article under the same title (37 U. Mich. J. L. Reform 1 (2003)), and adds an Addendum that accounts for subsequent amendments to the UPC’s elective share. As reported in the Addendum, the Uniform Law Commission adopted many of the changes recommended in the original Article.The elective share is a statutory provision common to most probate codes in non-community-property states. The elective share protects a decedent’s surviving spouse against disinheritance. Traditional elective share law typically grants a surviving spouse a right to elect one-third of the deceased spouse’s estate, increased in some states to one-half, but the theory behind the traditional elective share amount has not until recently been carefully scrutinized. A one-third fraction can only be explained as a carryover from common law dower, but whatever the cause in early English law for choosing that fraction, there is no justification for continuing to use that fraction today.There are two plausible theories for elective share law today. One is the marital sharing theory. Under that theory, marriage is viewed as an economic partnership, a view that implies a goal of equalizing the marital assets. The other plausible theory is the support theory, that the elective share is a means of continuing the decedent’s duty of support beyond the grave. The traditional elective share statute implements neither theory. A fixed fraction of the decedent’s estate, whether it be one-third or one-half, is not coordinated with the partnership or support theories. Regarding the partnership theory, one-third or one-half of the decedent’s estate might be significantly less than the amount necessary to equalize the marital assets when those assets are disproportionately titled in the decedent’s name and considerably in excess of the amount necessary to do so when those assets are already titled equally or are disproportionately titled in the survivor’s name. Regarding the support theory, one-third or one-half might be significantly less than the amount necessary to satisfy the survivor’s support needs in a smaller estate and considerably in excess of those needs in a larger estate.Other relevant areas of the law of marriage are based on and coordinated with both the partnership and support theories. In the community property states, property law implements the partnership theory during the marriage. Family law implements both the partnership and support theories – the partnership theory upon divorce through the equitable distribution regimes and the support theory through the duty of support during the marriage and the right to alimony upon divorce. Traditional elective share law is the odd one out. The 1990 UPC represented the first effort to bring elective share law broadly into line with the partnership theory of marriage. That theory suggests that, if the surviving spouse so elects, the survivor is entitled to force a transfer of the decedent’s assets sufficient to equalize the marital assets. In determining which portion of a decedent’s estate is marital, the 1990 UPC uses an approximation system. The 1990 UPC, however, suffered from problems of presentation. It presented the approximation system in a rather indirect and opaque form. The original Article recommended changes that would cure that defect in presentation. The primary benefit of the recommended changes was to make the statute, as revised, present the approximation system in a clear and transparent form. As reported in the Addendum, the Uniform Law Commission revised the UPC elective share in 2008 so that it now presents the elective share in a more direct and hence more understandable form than it was in its earlier formulation.

Relativistic smooth particle hydrodynamics on a given background spacetime

We review the derivation of fixed-metric, relativistic smooth particle hydrodynamics (SPH) from the Lagrangian of an ideal fluid. Combining the Euler–Lagrange equations with the first law of thermodynamics, we explicitly derive evolution equations for the canonical momentum and energy. This new set of SPH equations also accounts for corrective terms that result from derivatives of the SPH smoothing kernel and that are called ‘grad-h’ terms in non-relativistic SPH. The new equations differ from earlier formulations with respect to these corrective terms and the symmetries in the SPH particle indices while being identical in gravitational terms.

Ripple morphology under oscillatory flow: 1. Prediction

Recent laboratory and field experiments have shown the inability of existing oscillatory flow ripple predictors to accurately predict both ripple size and ripple planform geometry. However, at this time, only partial adaptations of these predictors have been proposed to account for the observed discrepancies with new experimental data. The present work starts by presenting a comprehensive data set compiled from 27 literature studies and our own experimental data, which are presented in a companion paper. Dimensional analysis is used both to clarify the importance of the different variables involved in the development of ripples and to generate the basic dimensionless framework for the study of ripple morphology under oscillatory flow. Several ripple size and planform geometry predictors are contrasted against the compiled data set. Afterward, a new ripple wavelength and height predictor and a new planform geometry predictor are proposed, which overcome several of the limitations found in the earlier formulations. The new predictors emphasize the existence of local and global sediment transport mechanisms over a ripple bed, each of them acting at different scales. In particular, sediment size is found to have an important effect on the size and geometry of bed forms that can be generated by oscillatory flows.