We consider two ways one might use algorithmic randomness to characterize a probabilistic law. The first is a generative chance* law. Such laws involve a nonstandard notion of chance. The second is a probabilistic* constraining law. Such laws impose relative frequency and randomness constraints that every physically possible world must satisfy. While each notion has virtues, we argue that the latter has advantages over the former. It supports a unified governing account of non-Humean laws and provides independently motivated solutions to (...) issues in the Humean best-system account. On both notions, we have a much tighter connection between probabilistic laws and their corresponding sets of possible worlds. Certain histories permitted by traditional probabilistic laws are ruled out as physically impossible. As a result, such laws avoid one variety of empirical underdetermination, but the approach reveals other varieties of underdetermination that are typically overlooked. (shrink)

Some metabolic pathways are nearly ubiquitous among organisms: the genes encoding the enzymes for such pathways must therefore be ancient and essential. De novo pyrimidine biosynthesis is an example of one such metabolic pathway. In animals a single protein called CADAbbreviations: CAD, trifunctional protein catalyzing the first three steps of de novo pyrimidine biosynthesis in higher eukaryotes; CPS, carbamyl phosphate synthetase domain; CPSase, carbamyl phosphate synthetase activity; ATC, aspartate transcarbamylase domain; ATCase, aspartate transcarbamylase activity; DHO, dihydroorotase domain; DHOase, dihydroorotase activity; (...) GLN, glutaminase subdomain or subunit of carbamyl phosphate synthetase, GL Nase, glutaminase activity; SYN, synthetase subdomain or subunit of carbamyl phosphate synthetase; SYNase, synthetase activity. carries the first three steps of this pathway. The same three enzymes in prokaryotes are associated with separate proteins. The CAD gene appears to have evolved through a process of gene duplication and DNA rearrangement, leading to an in‐frame gene fusion encoding a chimeric protein. A driving force for the creation of eukaryotic genes encoding multienzymatic proteins such as CAD may be the advantage of coordinate expression of enzymes catalyzing steps in a biosynthetic pathway. The analogous structure in bacteria is the operon. Differences in the translational mechanisms of eukaryotes and prokaryotes may have dictated the different strategies used by organisms to evolve coordinately regulated genes. (shrink)

The international pharmaceutical industry has made significant efforts towards ensuring compliant and ethical communication and interaction with physicians and patients. This article presents the current status of the worldwide governance of communication practices by pharmaceutical companies, concentrating on prescription-only medicines. It analyzes legislative, regulatory, and code-based compliance control mechanisms and highlights significant developments, including the 2006 and 2012 revisions of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Code of Practice.

Recent studies on the effects of mandatory online teaching, resulting from the COVID-19 pandemic, have widely reported low levels of satisfaction, unwillingness to continue online teaching, and negative impacts on the psychological well-being of teachers. Emerging research has highlighted the potential role of psychological need thwarting, in terms of autonomy, competence, and relatedness thwarting, resulting from online teaching. The aim of this study was to evaluate the immediate and delayed effects of PNT of online teaching on teachers’ well-being, intention to (...) continue online teaching, and job satisfaction. Moreover, data collected from both cross-sectional and longitudinal surveys allowed for a systematic validation of an important instrument in the field of teacher psychology, the Psychological Need Thwarting Scale of Online Teaching, in terms of longitudinal reliability and validity. The data reveal the usefulness of the construct of PNT in terms predicting and explaining teachers’ willingness to continue using online teaching as well as the degree of burnout after a period of 2 months, such that PNT is positively associated with burnout and negatively associated with willingness to continue online teaching. As such, the PNTSOT is recommended for future research evaluating the long-term psychological, affective, and intentional outcomes stemming from teachers’ PNT. Moreover, based on our findings that the impact from PNT of online teaching is persistent and long-term, we suggest that school leaders provide flexible and sustained professional development, model respectful and adaptive leadership, and create opportunities for mastery for the development of community of practice that can mitigate the thwarting of teachers’ autonomy, competence, and relatedness during times of uncertainty. Additionally, in terms of the psychometric properties of the PNTSOT instrument, our empirical findings demonstrate internal reliability, test–retest reliability, measurement invariance, and criterion validity based on cross-sectional and longitudinal data. (shrink)

To understand the ethical issue of gender inequality in entrepreneurial financing, we examine the effect of angel investors’ political ideology, the conservatism–liberalism continuum, on their investments in women-owned ventures. We propose that more conservative angel investors tend to have a lower percentage of investments in women-owned ventures in their portfolios. Moreover, drawing on the gender role congruity theory, we show that when investing in women-owned ventures, more conservative angels favor women-owned ventures with a higher percentage of male co-founders and operating (...) in women-dominated industries. Our analysis, based on a longitudinal sample of 172 angels from 2010 to 2019, supports these hypotheses. Our study contributes to the literature by highlighting angel political ideology as a critical antecedent of the gender disparity in entrepreneurial financing. (shrink)

Background: Monitoring the daily change in resting heart rate variability can provide information regarding training adaptation and recovery status of the autonomic nervous system during training camps. However, it remains unclear whether postural stabilization is essential for valid and reliable ultra-short-term recordings in short-term overseas training camps.Design: Observational and longitudinal study.Purpose: This study aimed to investigate ultra-short-term heart rate variability recordings under stabilization or post-stabilization periods in four overseas training camps.Participant: Twenty-seven U-20 male national team futsal players voluntarily participated in (...) this study.Method: Resting HRV was evaluated for 10 min during the early morning of each training camp. The natural logarithm of the root mean square of successive normal-to-normal interval differences was used for comparisons. Time segments of HRV were divided into two periods with three measures within each: the first 30-s, the first 60-s, and the 5-min standard during stabilization; the first 30-s, the first 60-s, and the 5-min standard after stabilization.Result: The results demonstrated trivial to small ES, very large to nearly perfect ICC, and narrow range of SEM when all time segments of HRVUST were compared to the 1st_5 min and 2nd_5 min HRV. Furthermore, the magnitude of the correlation coefficients ranged from very high to nearly perfect for all the time segments. The HRVUST posted excellent agreement in all time segments with/without postural stabilization. Trivial to small levels of effect size in all time segments of LnRMSSDmean and LnRMSSDcv across overseas training camps was identified.Conclusion: The first 30 or 60-s LnRMSSD recordings can be used to evaluate daily cardiac-autonomic function during overseas training camps in futsal players. The process for stabilization seems to be unnecessary for measuring the morning resting LnRMSSD in overseas training camps among young adult futsal players. (shrink)

A many-worlds interpretation is of quantum mechanics tells us that the linear equations of motion are the true and complete laws for the time-evolution of every physical system and that the usual quantum-mechanical states provide complete descriptions of all possible physical situations. Such an interpretation, however, denies the standard way of understanding quantum-mechanical states. When the pointer on a measuring device is in a superposition of pointing many different directions, for example, we are to understand this as many pointers, each (...) in a differentworld, each pointing in a different determinate direction. We ask here whether such talk makes any genuinely intelligible sense of the term world. We conclude that it does not. (shrink)

Ten years after the appearance of Günter Blamberger’s award-winning Heinrich von Kleist. Biographie in the original German, the English translation by Sebastian Goth and Kelly Kawar appeared in 202...

Kirchhoff’s 1882 theory of optical diffraction forms the centerpiece in the long-term development of wave optics, one that commenced in the 1820s when Fresnel produced an empirically successful theory based on a reinterpretation of Huygens’ principle, but without working from a wave equation. Then, in 1856, Stokes demonstrated that the principle was derivable from such an equation albeit without consideration of boundary conditions. Kirchhoff’s work a quarter century later marked a crucial, and widely influential, point for he produced Fresnel’s results (...) by means of Green’s theorem and function under specific boundary conditions. In the late 1880s, Poincaré uncovered an inconsistency between Kirchhoff’s conditions and his solution, one that seemed to imply that waves should not exist at all. Researchers nevertheless continued to use Kirchhoff’s theory—even though Rayleigh, and much later Sommerfeld, developed a different and mathematically consistent formulation that, however, did not match experimental data better than Kirchhoff’s theory. After all, Kirchhoff’s formula worked quite well in a specific approximation regime. Finally, in 1964, Marchand and Wolf employed the transformation of Kirchhoff’s surface integral that had been developed by Maggi and Rubinowicz for other purposes. The result yielded a consistent boundary condition that, while introducing a species of discontinuity, nevertheless rescued the essential structure of Kirchhoff’s original formulation from Poincaré’s paradox. (shrink)

Public conversation about biological contributors to mental disorder often centers on whether the problem is “biological or not.” In this paper, we propose moving beyond this bifurcation to a very different question:how exactlyare these problems understood to be biological? Specifically, we consider four issues around which different interpretations of the body’s relationship to mental disorder exist:1. The body’s relationship to day-to-day action; 2. The extent to which the body is changeable; 3. The body’s relationship to context; 4. The degree to (...) which states of the body directly cause mental disorder.Drawing on the work of Merleau-Ponty and other phenomenologists, we examine different responses to these questions and associated implications for how mental health treatment and recovery come to be experienced. Finally, we consider broader questions these patterns raise, including why certain portrayals of the brain dominate public attention and how to foster more deliberation in this regard. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

We examine the relationship between systems and their users from the knowledge discovery perspective. Recently knowledge discovery in databases has made important progress, but it may also bring some potential problems to database design, such as issues related to database security, because an unauthorised user may derive highly sensitive knowledge from unclassified data. In this paper we point out that there is a need for a comprehensive study on knowledge discovery in human-computer symbiosis. Borrowing terms from algorithm design and artificial (...) intelligence literature, we propose a notion called database-user adversarial partnership. We point out that this notion is general enough to cover various knowledge discovery and security of issues related to databases and their users. Furthermore, we point out the notion of database-user adversarial partnership can be further generalised into system-user adversarial partnership. Opportunities provided by knowledge discovery techniques and potential social implications are also discussed. (shrink)

In many research studies, tumor biopsies are an unavoidable requirement for achieving key scientific aims. Yet some commentators view mandatory research biopsies as coercive and suggest they should be optional, or at least optional until further data are obtained regarding their scientific usefulness. Further complicating the ethical picture is the fact that some research biopsies offer a potential for clinical benefit to trial participants. We interviewed and surveyed a convenience sample of participants in phase I clinical trials at a single (...) institution. Our primary aim was to describe phase I participants’ understanding of whether a research biopsy offered them the prospect of medical benefit. We also endeavored to describe participants’ views about biopsies—specifically, the benefits of biopsies, if any, and whether biopsies were acceptable, risky, or discouraged trial participation. Finally, we collected data on demographics and attitudes to see if any strong correlations with misunderstanding, acceptability, or riskiness existed. Overall, the respondents tended to view research biopsies as acceptable, though they did not succeed in identifying the lack of benefit of a research biopsy. These findings call for renewed efforts in consent conversations and documents to carefully describe the benefits, or lack thereof, of research biopsies. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

Commentary on Sakya Pandita's Tshad ma rigs gter; includes root text.

We prove that for a finitely generated infinite nilpotent group $G$ with structure $(G,\cdot,\dots)$, the connected component ${G^*}^0$ of a sufficiently saturated extension $G^*$ of $G$ exists and equals \[ \bigcap_{n\in\N} \{g^n\colon g\in G^*\}. \] We construct an expansion of ${\mathbb Z}$ by a predicate $({\mathbb Z},+,P)$ such that the type-connected component ${{\mathbb Z}^*}^{00}_{\emptyset}$ is strictly smaller than ${{\mathbb Z}^*}^0$. We generalize this to finitely generated virtually solvable groups. As a corollary of our construction we obtain an optimality result for (...) the van der Waerden theorem for finite partitions of groups. (shrink)

In Capitalism and the Jews, Jerry Z. Muller attempts to resolve Milton Friedman's paradox: Why is it that Jewish intellectuals have been so hostile to capitalism even though capitalism has so greatly benefited the Jews? In one chapter Muller answers, in effect, that Jewish intellectuals have not been anticapitalist. Elsewhere, however, Muller implicitly explains the leftist tendencies of most intellectuals—Jewish and gentile—by unspooling the anticapitalist thread in the main lines of Western thought, culminating in Marx but by no means ending (...) with him. Thus, Milton Friedman saw a paradox where none existed. This may have been because Friedman was an economist, and economics is the one strand of Western thought that is, by and large, procapitalist. To an economist, opposition to capitalism may be paradoxical; to noneconomists, economics is alienating in its form and in its content. There is thus no mystery as to why intellectuals, including Jewish intellectuals, tend to shun economics and therefore gravitate to the left. (shrink)

In Capitalism and the Jews, Jerry Z. Muller attempts to resolve Milton Friedman's paradox: Why is it that Jewish intellectuals have been so hostile to capitalism even though capitalism has so greatly benefited the Jews? In one chapter Muller answers, in effect, that Jewish intellectuals have not been anticapitalist. Elsewhere, however, Muller implicitly explains the leftist tendencies of most intellectuals—Jewish and gentile—by unspooling the anticapitalist thread in the main lines of Western thought, culminating in Marx but by no means ending (...) with him. Thus, Milton Friedman saw a paradox where none existed. This may have been because Friedman was an economist, and economics is the one strand of Western thought that is, by and large, procapitalist. To an economist, opposition to capitalism may be paradoxical; to noneconomists, economics is alienating in its form and in its content. There is thus no mystery as to why intellectuals, including Jewish intellectuals, tend to shun economics and therefore gravitate to the left. (shrink)

Explores and illuminates Slavoj Žižek's impact on our understanding of literary and cultural modernism.

Two papers in this issue address the limits of surrogates’ authority when making life-and-death decisions for dying family members or friends. Using palliative sedation as an example, Jeffrey Berger offers a conceptual argument for bounding surrogate authority. Since freedom from pain is an essential interest, when imminently dying, cognitively incapacitated patients are in duress and their symptoms are not manageable in any other way, clinicians should be free to offer palliative sedation without surrogate consent, although assent should be sought (...) and every effort made to work with surrogates as harmoniously as possible. Ellen Robinson and her colleagues report on the implementation of a policy at Massachusetts General Hospital that supports do-not-resuscitate orders when cardiopulmonary resuscitation is likely to be ineffective or harmful, even if surrogates disagree. The “Doing No Harm” policy at MGH allows for what MGH calls a “medically indicated DNR” and what in some other places is called “a unilateral DNR”—the writing of an order not to provide cardiopulmonary resuscitation, regardless of surrogate disapproval. These kinds of DNR policies have emerged in some hospitals across the country and for much the same reason that Berger provides in his argument regarding palliative sedation. I support the reasoning and the policies in both the Berger and Robinson papers. However, as the authors would most likely agree, the problems they aim to remedy are not simply about the scope of surrogate and professional authority. They are also symptoms of inattention to professional obligations and system failures. (shrink)

BackgroundCognitive frailty includes reversible and potentially reversible subtypes; the former is known as concurrent physical frailty and pre-mild cognitive impairment subjective cognitive decline, whereas the latter is known as concurrent PF and MCI. The diagnoses of pre-MCI SCD and MCI are based on clinical criteria and various subjective cognitive decline questionnaires. Heterogeneous assessment of cognitive impairment results in significant variability of CI, CF, and their subtype prevalence in various population-based studies.ObjectiveThis study aimed to compare the classification differences in CI and (...) CF subtypes from PF and normal cognition by applying clinical and objective cognitive criteria. Clinical criteria comprised Fried PF and clinical MCI criteria combined with the SCD questionnaire, whereas objective criteria comprised Fried PF and objective cognitive criteria based on the norm-adjusted six neuropsychological test scores.MethodsOf the 335 volunteers in this study, 191 were diagnosed with CI based on clinical cognitive diagnosis criteria, and 144 were identified as robust normal based on objective cognitive assessment from the community-dwelling older adult cohort. Individuals with clinical CI, including 94 with MCI and 97 with pre-MCI SCD, were reclassified into different z-score-derived MCI, pre-MCI SCD, and normal subgroups based on objective cognitive criteria. The classification diagnostic accuracy of normal cognition, PF, pre-MCI, MCI, CF, and CF subtypes based on clinical and objective criteria was compared before and after adjusting for age, sex, and education level.ResultsThe reclassification of objective assessments indicated better performance than that of clinical assessments in terms of discerning CI severity among different subgroups before adjusting for demographic factors. After covariate adjustment, clinical assessments significantly improved the ability to cognitively discriminate normal individuals from those with pre-MCI SCD and MCI but not the z-score-derived pre-MCI SCD and MCI groups from the robust normal group. Furthermore, the adjustment did not improve the ability to discriminate among individuals with reversible CF from those with potentially reversible CF and pre-MCI only SCD from MCI only SCD.ConclusionsObjective criteria showed better performance than clinical criteria in the diagnosis of individuals with CI or CF subtypes. Rapid clinical cognitive screening in combination with normative z-scores criteria is cost effective and sustainable in clinical practice. (shrink)