Thomas Young and Eighteenth-Century Tempi

The physician, natural philosopher, and linguist Thomas Young in 1800 provided a table of tempi gauged by a pendulum. Calibrated against Quantz’s pulse-based system (1752), Young’s observations quantitatively corroborate the generally faster contemporary tempi, while also indicating cases in which they should be moderated. His statement about the relative order of very slow and fast tempo markings contradict several contemporary English sources; as a natural philosopher, he brought special skill in observation to these controversies

Sounding Bodies

The unfolding influence of music and sound on the fundamental structure of the biomedical sciences, from ancient times to the present. Beginning in ancient Greece, Peter Pesic writes, music and sound significantly affected the development of the biomedical sciences. Physicians used rhythmical ratios to interpret the pulse, which inspired later efforts to record the pulse in musical notation. After 1700, biology and medicine took a “sonic turn,” viewing the body as a musical instrument, the rhythms and vibrations of which could guide therapeutic insight. In Sounding Bodies, Pesic traces the unfolding influence of music and sound on the fundamental structure of the biomedical sciences. Pesic explains that music and sound provided the life sciences important tools for hearing, understanding, and influencing the rhythms of life. As medicine sought to go beyond the visible manifestations of illness, sound offered ways to access the hidden interiority of body and mind. Sonic interventions addressed the search for a new typology of mental illness, and practitioners used musical instruments to induce hypnotic states meant to cure both psychic and physical ailments. The study of bat echolocation led to the manifold clinical applications of ultrasound; such sonic devices as telephones and tuning forks were used to explore the functioning of the nerves. Sounding Bodies follows Pesic's Music and the Making of Modern Science and Polyphonic Minds to complete a trilogy on the influence of music on the sciences. Enhanced digital editions of Sounding Bodies offer playable music and sound examples

Music, Melancholia, and Mania: Gaetano Brunetti's Obsessional Symphony

In his symphony “Il maníatico” (1780), Gaetano Brunetti gave a musical portrayal of monomania decades before it became a staple of nineteenth-century alienism (psychiatry), as well as of Romantic music and art. A detailed analysis of his symphony shows both the presenting features of what he called manía as well as the stages of the “maniac's” interaction with the surrounding “normal” world. These stages respond to widely known mental peculiarities of several generations of Spanish royalty, whom Brunetti served as court composer. Though its court audience would likely have compared this portrayal of obsession to Cervantes's Don Quixote, Brunetti's symphony may also have sent a coded message of sympathy to his patron, the crown prince who would later reign as Carlos IV and who struggled with his obsessional father, then reigning as Carlos III. At the same time, Brunetti mocked Luigi Boccherini, his rival as court composer. By presenting a subversive reimagining of the “normal” symphonic world, Brunetti characterized the mannerisms of classical style as monomania writ large. In the following decades, the term fixe Idee emerged in German literature and usage considerably before the French idée fixe. Both concepts emerged from literary, rather than medical, sources. Though Don Quixote remained a touchstone for reflections on “madness,” Brunetti's symphony anatomized obsession decades before medical discourse gave its clinical description

On Mathematics, Imagination and the Beauty of Numbers

Mathematic

Pharmacokinetic properties of remimazolam in subjects with hepatic or renal impairment

BACKGROUND: Remimazolam is a new benzodiazepine for procedural sedation and general anaesthesia. The aim of this study was to characterise its pharmacokinetic properties and safety in renally and hepatically impaired subjects. METHODS: Two separate trials were conducted in patients with hepatic (n=11) or renal impairment (n=11) compared with matched healthy subjects (n=9 and n=12, respectively). The hepatic impairment trial was an open-label adaptive 'Reduced Design' trial, using a single bolus of remimazolam 0.1 mg kg-1 i.v., whereas the renal impairment trial was an open-label trial of a single bolus dose of remimazolam 1.5 mg i.v. Remimazolam plasma concentrations over time were analysed by population pharmacokinetic modelling. RESULTS: Remimazolam pharmacokinetic properties were adequately described by a three-compartment, recirculatory model. Exposure in subjects with severe hepatic impairment was 38.1% higher (i.e. clearance was 38.1% lower) compared with healthy volunteers. This increase caused a slightly delayed recovery (8.0 min for healthy, 12.1 min for moderate, and 16.7 min for severe hepatic impairment). With renal impairment, plasma clearance was comparable with that measured in healthy subjects. Simulations of Cmax after a bolus dose of 10 mg showed no relevant impact of hepatic or renal impairment. The overall incidence of adverse events was low, and all adverse events were mild. CONCLUSIONS: As Cmax after a remimazolam bolus i.v. was not affected by hepatic or renal impairment, no dose adjustments are required. No unexpected adverse events related to remimazolam were seen in subjects with renal or hepatic impairment. CLINICAL TRIAL REGISTRATION: Hepatic impairment trial: ClinicalTrials.gov, NCT01790607 (https://clinicaltrials.gov/ct2/show/NCT01790607). Renal impairment trial: EudraCT Number: 2014-004575-23

Vitalism and the Resistance to Experimentation on Life in the Eighteenth Century

There is a familiar opposition between a ‘Scientific Revolution’ ethos and practice of experimentation, including experimentation on life, and a ‘vitalist’ reaction to this outlook. The former is often allied with different forms of mechanism – if all of Nature obeys mechanical laws, including living bodies, ‘iatromechanism’ should encounter no obstructions in investigating the particularities of animal-machines – or with more chimiatric theories of life and matter, as in the ‘Oxford Physiologists’. The latter reaction also comes in different, perhaps irreducibly heterogeneous forms, ranging from metaphysical and ethical objections to the destruction of life, as in Margaret Cavendish, to more epistemological objections against the usage of instruments, the ‘anatomical’ outlook and experimentation, e.g. in Locke and Sydenham. But I will mainly focus on a third anti-interventionist argument, which I call ‘vitalist’ since it is often articulated in the writings of the so-called Montpellier Vitalists, including their medical articles for the Encyclopédie. The vitalist argument against experimentation on life is subtly different from the metaphysical, ethical and epistemological arguments, although at times it may borrow from any of them. It expresses a Hippocratic sensibility – understood as an artifact of early modernity, not as some atemporal trait of medical thought – in which Life resists the experimenter, or conversely, for the experimenter to grasp something about Life, it will have to be without torturing or radically intervening in it. I suggest that this view does not have to imply that Nature is something mysterious or sacred; nor does the vitalist have to attack experimentation on life in the name of some ‘vital force’ – which makes it less surprising to find a vivisectionist like Claude Bernard sounding so close to the vitalists

Simulating rewetting events in intermittent rivers and ephemeral streams: a global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56‐98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached organic matter. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and the ex‐ tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (precon‐ ditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experi‐ mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐ bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative character‐ istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dis‐ solved substances during rewetting events (56%–98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐ uted most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐ ables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached sub‐ stances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying event