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The work of Ed Zigler spans decades of research all singularly dedicated to using science to improve the lives of children facing different challenges. The focus of this article is on one of Zigler's numerous lines of work: advocating for the practice of mental age (MA) matching in empirical research, wherein groups of individuals are matched on the basis of developmental level, rather than chronological age. While MA matching practices represented a paradigm shift that provided the seeds from which the developmental approach to developmental disability sprouted, it is not without its own limits. Here, we examine and test the underlying assumption of linearity inherent in MA matching using three commonly used IQ measures. Results provide practical constraints of using MA matching, a solution which we hope refines future clinical and empirical practices, furthering Zigler's legacy of continued commitment to compassionate, meaningful, and rigorous science in the service of children.
The main body of this Element, about Kant's theory of conscience, is divided into two sections. The first focuses on exegesis of Kant's ethics. One of the overarching theses of this section of the Element is that, although many of Kant's claims about conscience are prima facie inconsistent, a close examination of context generally can dissolve apparent contradictions. The second section of the Element focuses on philosophical issues in Kantian ethics. One of the overarching theses of this section of the Element is that many positions traditionally associated with Kantian ethics, including the denial of moral luck, the nonaccidental rightness condition, and the guise of the objectively good, are at variance with Kant's ethics.
Combination olanzapine and samidorphan (OLZ/SAM) is in development for treatment of schizophrenia and bipolar I disorder and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension study (NCT02873208; ENLIGHTEN-2-EXT) in schizophrenia assessed the safety and tolerability of OLZ/SAM. Methods: Patients completing the 24-week, randomized, double-blind, phase 3 ENLIGHTEN−2 study comparing weight gain with OLZ/SAM vs olanzapine were eligible for ENLIGHTEN-2-EXT enrollment. Initial OLZ/SAM doses were based on olanzapine dose (10 or 20 mg) received at the conclusion of ENLIGHTEN-2; subsequent olanzapine dose adjustments were allowed. The samidorphan dose (10 mg) remained fixed throughout. Assessments included adverse events (AEs), weight, waist circumference, metabolic laboratory parameters, and Positive and Negative Syndrome Scale (PANSS) scores. Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.
265 patients received OLZ/SAM; 167 (63.0%) completed the extension study. Common AEs (= 5%) were weight decreased (n=23; 8.7%), extra dose administered (n=21; 7.9%), headache (n=18; 6.8%), and weight increased (n=16; 6.0%). At week 52, mean (SD) change from baseline for weight and waist circumference was −0.03 (6.216) kg and −0.35 (6.115) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. PANSS total scores remained stable during the extension.
OLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.
A family of vectors in [k]n is said to be intersecting if any two of its elements agree on at least one coordinate. We prove, for fixed k ≥ 3, that the size of any intersecting subfamily of [k]n invariant under a transitive group of symmetries is o(kn), which is in stark contrast to the case of the Boolean hypercube (where k = 2). Our main contribution addresses limitations of existing technology: while there are now methods, first appearing in work of Ellis and the third author, for using spectral machinery to tackle problems in extremal set theory involving symmetry, this machinery relies crucially on the interplay between up-sets, biased product measures, and threshold behaviour in the Boolean hypercube, features that are notably absent in the problem considered here. To circumvent these barriers, introducing ideas that seem of independent interest, we develop a variant of the sharp threshold machinery that applies at the level of products of posets.
This chapter analyzes the public research system and policies implemented in South Africa to promote innovation and economic development. In addition to public research organizations and state-owned enterprises, the government research and innovation infrastructure is supplemented with private sector research, regulatory bodies, industry associations, and the South African Patent Office in South Africa. The chapter describes South African policies that have been introduced to support the supply of public research, consisting of the outputs of public research organizations, policies to support the innovative capabilities of firms, and policies to support linkages and knowledge transfer between public research and firms. Four case studies based on desk research and interviews show that the main channels for knowledge transfer in South Africa are informal methods and research agreements. The chapter concludes that a number of factors have limited the flow of knowledge from public research to businesses in South Africa and action is required to improve the demand for university research and increase the domestic capability to absorb and learn how to use technologies associated with new investment and modernization.
Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders.
We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a de novo 22q11.2 deletion (22 with schizophrenia), and 148 of their unaffected parents. We calculated within-family correlations and effect sizes of the 22q11.2 deletion and schizophrenia, and used linear regressions to assess contributions to neurobehavioral measures.
Proband-parent intra-class correlations (ICC) were significant for cognitive measures (e.g. FSIQ ICC = 0.549, p < 0.0001), but not for social or motor measures. Compared to biparental scores, the 22q11.2 deletion conferred significant impairments for all phenotypes assessed (effect sizes −1.39 to −2.07 s.d.), strongest for PIQ. There were further decrements in those with schizophrenia. Regression models explained up to 37.7% of the variance in IQ and indicated that for proband IQ, parental IQ had larger effects than schizophrenia.
This study, for the first time, disentangles the impact of a high-impact variant from the modifying effects of parental scores and schizophrenia on relevant neurobehavioral phenotypes. The robust proband-parent correlations for cognitive measures, independent of the impact of the 22q11.2 deletion and of schizophrenia, suggest that, for certain phenotypes, shared genetic variation plays a significant role in expression. Molecular genetic and predictor studies are needed to elucidate shared factors and their contribution to psychiatric illness in this and other high-risk groups.
The aim of this study was to determine if magnetic resonance-guided focused ultrasound (MRgFUS) is cost-effective compared with medication, for refractory pain from bone metastases in the United States.
We constructed a Markov state transition model using TreeAge Pro software (TreeAge Software, Inc., Williamstown, MA, USA) to model costs, outcomes, and the cost-effectiveness of a treatment strategy using MRgFUS for palliative treatment of painful bone metastases compared with a Medication Only strategy (Figure 1). Model transition state probabilities, costs (in 2018 US$), and effectiveness data (quality-adjusted life-years [QALYs]) were derived from available literature, local expert opinion, and reimbursement patterns at two U.S. tertiary academic medical centers actively performing MRgFUS. Costs and QALYs, discounted at three percent per year, were accumulated each month over a 24-month time horizon. One-way and probabilistic sensitivity analyses were performed.
In the base-case analysis, the MRgFUS treatment strategy costs an additional $11,863 over the 2-year time horizon to accumulate additional 0.22 QALYs, equal to a $54,160/QALY ICER, thus making MRgFUS the preferred strategy. One-way sensitivity analyses demonstrate that for the base-case analysis, the crossover point at which Medication Only would instead become the preferred strategy is $23,341 per treatment. Probabilistic sensitivity analyses demonstrate that 67 percent of model iterations supported the conclusion of the base case.
Our model demonstrates that MRgFUS is cost-effective compared with Medication Only for palliation of painful bone metastases for patients with medically refractory metastatic bone pain across a range of sensitivity analyses.
A pandemic arises when biology meets politics. The biology may be universal, but politics are local. Some nations suffer many thousands of deaths; some hundreds. Same virus; different politics. Economic development accounts for some of the differences, but even nations at the same level of development can have radically different pandemics. If politics is destiny, then our fate is in our hands.
The threat of the coronavirus to a community raises a political question: What is the nation prepared to do? In the United States and the United Kingdom, the initial answer was “very little.” Other places – for example, China, Israel, or South Korea – were prepared to do quite a lot. The statistics show the consequences.
The best apocalyptic movies (from Mad Max to The Stalker) are less about the apocalypse than what follows it. They focus on the systemic changes triggered by the apocalypse. About the apocalypse itself, little can be said. Speech begins again with survival. Likewise, in the middle of the current pandemic, we operate under the law of necessity. For this reason, nations with very different political systems have converged on the same practices of lockdown, social distancing, testing, and tracing. Nations that refuse to accept the law of necessity demonstrate not political strength, but weakness. They suffer the consequences, for the virus recognizes no excuses. Consider the ravages of the pandemic in Brazil and the United States.
The COVID-19 pandemic has presented an important case study, on a global scale, of how democracy works - and fails to work - today. From leadership to citizenship, from due process to checks and balances, from globalization to misinformation, from solidarity within and across borders to the role of expertise, key democratic concepts both old and new are now being put to the test. The future of democracy around the world is at issue as today's governments manage their responses to the pandemic. Bringing together some of today's most creative thinkers, these essays offer a variety of inquiries into democracy during the global pandemic with a view to imagining post-crisis political conditions. Representing different regions and disciplines, including law, politics, philosophy, religion, and sociology, eighteen voices offer different outlooks - optimistic and pessimistic - on the future.
The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias.
A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses.
MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = −0.42) and underestimation (e.g. magical thinking, d = −0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition.
Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.
The narrative Source BII includes a meeting of three Assyrian commanders accompanied by a large army with a Judean delegation at the conduit of the upper pool on the highway at the Fuller’s Field. Rāb-šaqê conveys to Hezekiah’s emissaries a message. He warns them not to rebel against Assyria, not to confront the Assyrian army with the aid of the Egyptians in a pitched battle, and not to trust YHWH for deliverance, since YHWH has allegedly sent Sennacherib to devastate the land of Judah. When Hezekiah sends a delegation to Isaiah to ask for YHWH’s aid, Isaiah delivers an oracle assuring the king of Judah not to fear, for a spirit will be given to the king of Assyria. He will hear a rumor, retreat to Assyria, and die by the sword. Source BII focuses on the murder of Sennacherib, on the Egyptian aid in a pitched battle, and mentions Taharqa, king of Kush, who would cause Sennacherib to retreat. The motifs of divine intervention, causing Assyria’s defeat and Sennacherib’s retreat and eventual murder, are the backbone of Source BII.