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The oral route is the most common choice for drug administration because of several advantages, such as convenience, low cost, and high patient compliance, and the demand and investment in research and development for oral drugs continue to grow. The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by gastric motility, physical properties of the pill, and the contents of the stomach, but current in vitro procedures for assessing dissolution of oral drugs are limited in their ability to recapitulate this process. This is particularly relevant for disease conditions, such as gastroparesis, that alter the anatomy and/or physiology of the stomach. In silico models of gastric biomechanics offer the potential for overcoming these limitations of existing methods. In the current study, we employ a biomimetic in silico simulator based on the realistic anatomy and morphology of the stomach (referred to as “StomachSim”) to investigate and quantify the effect of body posture and stomach motility on drug bioavailability. The simulations show that changes in posture can potentially have a significant (up to 83%) effect on the emptying rate of the API into the duodenum. Similarly, a reduction in antral contractility associated with gastroparesis can also be found to significantly reduce the dissolution of the pill as well as emptying of the API into the duodenum. The simulations show that for an equivalent motility index, the reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis. 

Productivity tracking tools often determine productivity based on the time interacting with work-related applications. To deconstruct productivity’s diverse and nebulous nature, we investigate how knowledge workers conceptualize personal productivity and delimit productive tasks in both work and non-work contexts. We report a 2-week diary study followed by a semi-structured interview with 24 knowledge workers. Participants captured productive activities and provided the rationale for why the activities were assessed to be productive. They reported a wide range of productive activities beyond typical desk-bound work—ranging from having a personal conversation with dad to getting a haircut. We found six themes that characterize the productivity assessment—work product, time management, worker’s state, attitude toward work, impact & benefit, and compound task—and identified how participants interleaved multiple facets when assessing their productivity. We discuss how these findings could inform the design of a comprehensive productivity tracking system that covers a wide range of productive activities. 

Abstract The Gravitational-Wave Transient Catalog (GWTC) is a collection of short-duration (transient) gravitational-wave signals identified by the LIGO–Virgo–KAGRA Collaboration in gravitational-wave data produced by the eponymous detectors. The catalog provides information about the identified candidates, such as the arrival time and amplitude of the signal and properties of the signal’s source as inferred from the observational data. GWTC is the data release of this dataset, and version 4.0 extends the catalog to include observations made during the first part of the fourth LIGO–Virgo–KAGRA observing run up until 2024 January 31. This Letter marks an introduction to a collection of articles related to this version of the catalog, GWTC-4.0. The collection of articles accompanying the catalog provides documentation of the methods used to analyze the data, summaries of the catalog of events, observational measurements drawn from the population, and detailed discussions of selected candidates. 

Abstract We report the observation of gravitational waves from two binary black hole coalescences during the fourth observing run of the LIGO–Virgo–KAGRA detector network, GW241011 and GW241110. The sources of these two signals are characterized by rapid and precisely measured primary spins, nonnegligible spin–orbit misalignment, and unequal mass ratios between their constituent black holes. These properties are characteristic of binaries in which the more massive object was itself formed from a previous binary black hole merger and suggest that the sources of GW241011 and GW241110 may have formed in dense stellar environments in which repeated mergers can take place. As the third-loudest gravitational-wave event published to date, with a median network signal-to-noise ratio of 36.0, GW241011 furthermore yields stringent constraints on the Kerr nature of black holes, the multipolar structure of gravitational-wave generation, and the existence of ultralight bosons within the mass range 10⁻¹³–10⁻¹²eV. 

Abstract On 2023 November 23, the two LIGO observatories both detected GW231123, a gravitational-wave signal consistent with the merger of two black holes with masses $137_{-18}^{+23}{M}_{\odot }$and $101_{-50}^{+22}{M}_{\odot }$(90% credible intervals), at a luminosity distance of 0.7–4.1 Gpc, a redshift of $0.40_{-0.25}^{+0.27}$, and with a network signal-to-noise ratio of ∼20.7. Both black holes exhibit high spins— $0.90_{-0.19}^{+0.10}$and $0.80_{-0.52}^{+0.20}$, respectively. A massive black hole remnant is supported by an independent ringdown analysis. Some properties of GW231123 are subject to large systematic uncertainties, as indicated by differences in the inferred parameters between signal models. The primary black hole lies within or above the theorized mass gap where black holes between 60–130M_⊙should be rare, due to pair-instability mechanisms, while the secondary spans the gap. The observation of GW231123 therefore suggests the formation of black holes from channels beyond standard stellar collapse and that intermediate-mass black holes of mass ∼200M_⊙form through gravitational-wave-driven mergers. 

A search for proton decay into $e^{+}/{\mu }^{+}$and a $\eta$meson has been performed using data from a $0.373\mathrm{Mton}·\mathrm{year}$exposure (6050.3 live days) of Super-Kamiokande. Compared to previous searches this work introduces an improved model of the intranuclear $\eta$interaction cross section, resulting in a factor of 2 reduction in uncertainties from this source and $\sim 10\%$increase in signal efficiency. No significant data excess was found above the expected number of atmospheric neutrino background events resulting in no indication of proton decay into either mode. Lower limits on the proton partial lifetime of $1.4\times {10}^{34}\mathrm{years}$for $p\to e^{+}\eta$and $7.3\times {10}^{33}\mathrm{years}$for $p\to {\mu }^{+}\eta$at the 90% CL were set. These limits are around 1.5 times longer than our previous study and are the most stringent to date. Published by the American Physical Society2024