On bullshit Frankfurt, Harry G
2005., 20090110, 2009, 2005, 2005-12-31
eBook
One of the most salient features of our culture is that there is so much bullshit. Everyone knows this. Each of us contributes his share. But we tend to take the situation for granted. Most people ...are rather confident of their ability to recognize bullshit and to avoid being taken in by it. So the phenomenon has not aroused much deliberate concern. We have no clear understanding of what bullshit is, why there is so much of it, or what functions it serves. And we lack a conscientiously developed appreciation of what it means to us. In other words, as Harry Frankfurt writes, "we have no theory." Frankfurt, one of the world’s most influential moral philosophers, attempts to build such a theory here. With his characteristic combination of philosophical acuity, psychological insight, and wry humor, Frankfurt proceeds by exploring how bullshit and the related concept of humbug are distinct from lying. He argues that bullshitters misrepresent themselves to their audience not as liars do, that is, by deliberately making false claims about what is true. In fact, bullshit need not be untrue at all.
Microglia are critical nervous system-specific cells influencing brain development, maintenance of the neural environment, response to injury, and repair. They contribute to neuronal proliferation ...and differentiation, pruning of dying neurons, synaptic remodeling and clearance of debris and aberrant proteins. Colonization of the brain occurs during gestation with an expansion following birth with localization stimulated by programmed neuronal death, synaptic pruning, and axonal degeneration. Changes in microglia phenotype relate to cellular processes including specific neurotransmitter, pattern recognition, or immune-related receptor activation. Upon activation, microglia cells have the capacity to release a number of substances, e.g., cytokines, chemokines, nitric oxide, and reactive oxygen species, which could be detrimental or beneficial to the surrounding cells. With aging, microglia shift their morphology and may display diminished capacity for normal functions related to migration, clearance, and the ability to shift from a pro-inflammatory to an anti-inflammatory state to regulate injury and repair. This shift in microglia potentially contributes to increased susceptibility and neurodegeneration as a function of age. In the current review, information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging.
A worldwide cardiac pacing and implantable cardioverter‐defibrillator (ICD) survey was undertaken for calendar year 2009 and compared to a similar survey conducted in 2005. There were contributions ...from 61 countries: 25 from Europe, 20 from the Asia Pacific region, seven from the Middle East and Africa, and nine from the Americas. The 2009 survey involved 1,002,664 pacemakers, with 737,840 new implants and 264,824 replacements. The United States of America (USA) had the largest number of cardiac pacemaker implants (225,567) and Germany the highest new implants per million population (927). Virtually all countries showed increases in implant numbers over the 4 years between surveys. High‐degree atrioventricular block and sick sinus syndrome remain the major indications for implantation of a cardiac pacemaker. There remains a high percentage of VVI(R) pacing in the developing countries, although compared to the 2005 survey, virtually all countries had increased the percentage of DDDR implants. Pacing leads were predominantly transvenous, bipolar, and active fixation. The survey also involved 328,027 ICDs, with 222,407 new implants and 105,620 replacements. Virtually all countries surveyed showed a significant rise in the use of ICDs with the largest implanter being the USA (133,262) with 434 new implants per million population. This was the largest pacing and ICD survey ever performed, because of mainly a group of loyal enthusiastic survey coordinators. It encompasses more than 80% of all the pacemakers and ICDs implanted worldwide during 2009. (PACE 2011; 34:1013–1027)
This beautifully written book by one of the world's leading moral philosophers argues that the key to a fulfilled life is to pursue wholeheartedly what one cares about, that love is the most ...authoritative form of caring, and that the purest form of love is, in a complicated way, self-love. Harry Frankfurt writes that it is through caring that we infuse the world with meaning. Caring provides us with stable ambitions and concerns; it shapes the framework of aims and interests within which we lead our lives. The most basic and essential question for a person to raise about the conduct of his or her life is not what he or she should care about but what, in fact, he or she cannot help caring about.
We report a record-high SO2 adsorption capacity of 12.3 mmol g–1 in a robust porous material, MFM-601, at 298 K and 1.0 bar. SO2 adsorption in MFM-601 is fully reversible and highly selective over ...CO2 and N2. The binding domains for adsorbed SO2 and CO2 molecules in MFM-601 have been determined by in situ synchrotron X-ray diffraction experiments, giving insights at the molecular level to the basis of the observed high selectivity.
Solid crystalline phases containing two cocrystallized components offer a new development pathway whereby one can potentially improve the physical characteristics (i.e., equilibrium solubility, ...dissolution rate, solid-state stability, etc.) of a drug substance that exhibits a profile that is less than desirable. In this commentary, the topic of pharmaceutical cocrystals will be briefly explored, and a short exposition of the solubility and dissolution rate advantages that have been realized in various systems will be provided. The Guidance for Industry document recently proposed by United States Food and Drug Administration will be outlined, and its requirements explained. Finally, the subset of pharmaceutical cocrystals that consist of a drug substance and a salt of that substance (termed a salt cocrystal) will be examined to illustrate this additional class of pharmaceutical cocrystals that may offer significant scientific and regulatory advantages.
ABSTRACTBanyard, HG, Nosaka, K, and Haff, GG. Reliability and validity of the load–velocity relationship to predict the 1RM back squat. J Strength Cond Res 31(7)1897–1904, 2017—This study ...investigated the reliability and validity of the load–velocity relationship to predict the free-weight back squat one repetition maximum (1RM). Seventeen strength-trained males performed three 1RM assessments on 3 separate days. All repetitions were performed to full depth with maximal concentric effort. Predicted 1RMs were calculated by entering the mean concentric velocity of the 1RM (V1RM) into an individualized linear regression equation, which was derived from the load–velocity relationship of 3 (20, 40, 60% of 1RM), 4 (20, 40, 60, 80% of 1RM), or 5 (20, 40, 60, 80, 90% of 1RM) incremental warm-up sets. The actual 1RM (140.3 ± 27.2 kg) was very stable between 3 trials (ICC = 0.99; SEM = 2.9 kg; CV = 2.1%; ES = 0.11). Predicted 1RM from 5 warm-up sets up to and including 90% of 1RM was the most reliable (ICC = 0.92; SEM = 8.6 kg; CV = 5.7%; ES = −0.02) and valid (r = 0.93; SEE = 10.6 kg; CV = 7.4%; ES = 0.71) of the predicted 1RM methods. However, all predicted 1RMs were significantly different (p ≤ 0.05; ES = 0.71–1.04) from the actual 1RM. Individual variation for the actual 1RM was small between trials ranging from −5.6 to 4.8% compared with the most accurate predictive method up to 90% of 1RM, which was more variable (−5.5 to 27.8%). Importantly, the V1RM (0.24 ± 0.06 m·s) was unreliable between trials (ICC = 0.42; SEM = 0.05 m·s; CV = 22.5%; ES = 0.14). The load–velocity relationship for the full depth free-weight back squat showed moderate reliability and validity but could not accurately predict 1RM, which was stable between trials. Thus, the load–velocity relationship 1RM prediction method used in this study cannot accurately modify sessional training loads because of large V1RM variability.
We develop new theory and hypotheses on how a firm's top management team learns from acquisition experience, why, in consequence, the composition of the team is crucial, and how this affects ...acquisition frequency and success. We focus on the diversity of the top team and argue that heterogeneous teams, as compared to homogenous ones, acquire less but benefit more from their acquisition experience and are more successful with their acquisitions because they avoid mis-transferring their experiences. We tested our hypotheses on acquisition frequency and success using longitudinal data on more than 2,000 acquisitions by 25 Dutch companies over four decades (1966 to 2006).
Resetting of the epigenome in human primordial germ cells (hPGCs) is critical for development. We show that the transcriptional program of hPGCs is distinct from that in mice, with co-expression of ...somatic specifiers and naive pluripotency genes TFCP2L1 and KLF4. This unique gene regulatory network, established by SOX17 and BLIMP1, drives comprehensive germline DNA demethylation by repressing DNA methylation pathways and activating TET-mediated hydroxymethylation. Base-resolution methylome analysis reveals progressive DNA demethylation to basal levels in week 5–7 in vivo hPGCs. Concurrently, hPGCs undergo chromatin reorganization, X reactivation, and imprint erasure. Despite global hypomethylation, evolutionarily young and potentially hazardous retroelements, like SVA, remain methylated. Remarkably, some loci associated with metabolic and neurological disorders are also resistant to DNA demethylation, revealing potential for transgenerational epigenetic inheritance that may have phenotypic consequences. We provide comprehensive insight on early human germline transcriptional network and epigenetic reprogramming that subsequently impacts human development and disease.
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•SOX17-BLIMP1 with TFCP2L1 and KLF4 constitute a unique hPGC transcriptome•hPGC transcriptome drives extensive DNA demethylation and chromatin reorganization•Evolutionarily young and hazardous retrotransposons remain partially methylated•Some demethylation resistant loci are candidates for epigenetic inheritance
A unique transcriptome drives extensive epigenome resetting in human primordial germ cells for establishment of totipotency. Some loci associated with metabolic and neurological disorders exhibit resistance to reprogramming and are candidates for transgenerational epigenetic inheritance.
The temporal and spatial pattern of microglia colonization and vascular infiltration of the nervous system implies critical associated roles in early stages of nervous system development. Adding to ...existing reviews that cover a broad spectrum of the various roles of microglia during brain development, the current review will focus on the developmental ontogeny and interdependency between the colonization of the nervous system with yolk sac derived macrophages and vascularization. Gaining a better understanding of the timing and the interdependency of these two processes will significantly contribute to the interpretation of data generated regarding alterations in either process during early development. Additionally, such knowledge should provide a framework for understanding the influence of the early gestational environmental and the impact of genetics, disease, disorders, or exposures on the early developing nervous system and the potential for long-term and life-time effects.
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