Observational constraints on the neutron star mass distribution

Radio observations of neutron star binary pulsar systems have constrained strongly the masses of eight neutron stars. Assuming neutron star masses are uniformly distributed between lower and upper bounds $m_l$ and $m_u$, the observations determine with 95\% confidence that $1.01 < m_l/\text{M}_\odot < 1.34$ and $1.43 < m_u/\text{M}_\odot < 1.64$. These limits give observational support to neutron star formation scenarios that suggest that masses should fall predominantly in the range $1.3<m/\text{M}_\odot<1.6$, and will also be important in the interpretation of binary inspiral observations by the Laser Interferometer Gravitational-wave Observatory.Comment: Postscript, 4 pages, NU-GR-

Impact of Endogenous Bile Salts on the Thermodynamics of Supersaturated Active Pharmaceutical Ingredient Solutions

A variety of formulation strategies have been developed to mitigate the inadequate aqueous solubility of certain therapeutic agents. Among these, achieving supersaturation in vivo is a promising approach to improve the extent of oral absorption. Because of the thermodynamic instability of supersaturated solutions, inhibitors are needed to kinetically hinder crystallization. In addition to commonly used polymeric additives, bile salts, naturally present in the gastrointestinal tract, have been shown to exhibit crystallization inhibition properties. However, the impact of bile salts on solution thermodynamics is not well understood, although this knowledge is essential in order to explore the mechanism of crystallization inhibition. To better describe solution thermodynamics in the presence of bile salts, a side-by-side diffusion cell was used to evaluate solute flux for solutions of telaprevir in the absence and presence of the six most abundant bile salts in human intestinal fluid at various solute concentrations; flux measurements provide information about the solute thermodynamic activity and hence can provide an improved measurement of supersaturation in complex solutions. Trihydroxy bile salts had minimal impact on solution phase boundaries as well as solute flux, while micellar dihydroxy bile salts solubilized telaprevir leading to reduced solute flux across the membrane. An inconsistency between the concentration-based supersaturation ratio and that based on solute thermodynamic activity (the fundamental driving force for crystallization) was noted, suggesting that the activity-based supersaturation should be determined to better interpret any modification in crystallization kinetics in the presence of these additives. These findings indicate that bile salts are not interchangeable from a thermodynamic perspective and provide a foundation for further studies evaluating the mechanism of crystallization inhibition

From bound states to resonances: analytic continuation of the wave function

Single-particle resonance parameters and wave functions in spherical and deformed nuclei are determined through analytic continuation in the potential strength. In this method, the analyticity of the eigenvalues and eigenfunctions of the Schroedinger equation with respect to the coupling strength is exploited to analytically continue the bound-state solutions into the positive-energy region by means of Pade' approximants of the second kind. The method is here applied to single-particle wave functions of the $^{154}Sm$ and $^{131}Eu$ nuclei. A comparison of the results with the direct solution of the Schroedinger equation shows that the method can be confidently applied also in coupled-channel situations requiring high numerical accuracy.Comment: 13 pages, 3 figure

Did the London Initiative Zone investment programme affect general practice structure and performance in East London? A time series analysis of cervical screening coverage and asthma prescribing

A programme of incentives was set up in the London Initiative Zones to improve primary care in inner London based on the findings of the Tomlinson Enquiry in 1992. This descriptive study is a 4-y time series analysis of changes in general practice structure in East London as the result of London Initiative Zone investment, and an exploration of the possible effect of investment on practice performance.We used routinely available administrative data for the whole analysis. General practice characteristics and two selected performance indicators: the asthma prophylaxis to bronchodilator ratio and cervical cytology screening rate, for all practices in the East London and the City Health Authority for 4 y, 1993-1996, were used. Both reflect practice efficiency, but relate to different aspects of practice performance. The prescribing indicator is more indicative of the quality of clinical practise, whereas cervical screening coverage relates more to the characteristics of the practice population and to practice organisation. Repeated measures analyses were used to identify trends and to explore the relationship between changes in practice characteristics and performance. Graphical methods were used to compare East London trends with the rest of England.There were significant improvements in practice structure as the consequence of London Initiative Zone investment. There was a positive association with improvements in practice performance, but East London still lagged some way behind national patterns. The findings suggest that while improvements in asthma prescribing follow the national trend, practices have difficulty in achieving and sustaining the 80% target for cervical cytology screening, and that an overall population coverage of 80% may be in doubt.Increased investment in practice staffing may be influential in improving some aspects of performance. However, in common with other inner cities, a greater effort and more innovative strategies may be needed to achieve a standard of performance equal to the best

Associations between personal care product use patterns and breast cancer risk among white and black women in the sister study

BACKGROUND: Many personal care products include chemicals that might act as endocrine disruptors and thus increase the risk of breast cancer. OBJECTIVE: We examined the association between usage patterns of beauty, hair, and skin-related personal care products and breast cancer incidence in the Sister Study, a national prospective cohort study (enrollment 2003–2009). METHODS: Non-Hispanic black (4,452) and white women (n = 42,453) were examined separately using latent class analysis (LCA) to identify groups of individuals with similar patterns of self-reported product use in three categories (beauty, skin, hair). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between product use and breast cancer incidence. RESULTS: A total of 2,326 women developed breast cancer during follow-up (average follow-up = 5:4 y). Among black women, none of the latent class hazard ratios was elevated, but there were <100 cases in any category, limiting power. Among white women, those classified as “moderate” and “frequent” users of beauty products had increased risk of breast cancer relative to “infrequent” users [HR = 1:13 (95% CI: 1.00, 1.27) and HR = 1:15 (95% CI: 1.02, 1.30), respectively]. Frequent users of skincare products also had increased risk of breast cancer relative to infrequent users [HR = 1:13 (95% CI: 1.00, 1.29)]. None of the hair product classes was associated with increased breast cancer risk. The associations with beauty and skin products were stronger in postmenopausal women than in premenopausal women, but not significantly so. CONCLUSIONS: This work generates novel hypotheses about personal care product use and breast cancer risk. Whether these results are due to specific chemicals or to other correlated behaviors needs to be evaluated. https://doi.org/10.1289/EHP1480

Maintaining Supersaturation of Active Pharmaceutical Ingredient Solutions with Biologically Relevant Bile Salts

Currently, it is of interest to improve the oral absorption of poorly water-soluble therapeutic agents using supersaturating formulations. Understanding crystallization kinetics of supersaturated drug solutions is central to the design and evaluation of such formulations. Bile salts have drawn increasing attention in this context as they serve important roles in biorelevant dissolution media, in vivo, and have been shown to slow down the crystallization of active pharmaceutical ingredients. The goal of this study was to evaluate the impact of bile salt monomers and micelles on the crystallization of telaprevir, a poorly water-soluble drug, from aqueous solution. To better describe the crystallization driving force in the presence of the bile salts, a side-by-side diffusion cell was used to evaluate telaprevir mass flow rate, and hence solute activity, in the absence and presence of different bile salts. The effectiveness of monomeric and miceller bile salts as crystallization inhibitors was then evaluated by performing crystallization induction time experiments at constant, activity-based supersaturation. The six most abundant biologically relevant bile salts were investigated (sodium taurocholate, sodium taurodeoxycholate, sodium taurochenodeoxycholate, sodium glycocholate, sodium glycodeoxycholate, and sodium glycochenodeoxycholate). All six bile salts exhibited nucleation inhibition properties in both homogeneous supersaturated telaprevir solutions and highly supersaturated telaprevir solutions containing a second phase. The ability to retard telaprevir nucleation, however, varied among the bile salts and also depended on the aggregation state. Monomeric bile salts were found to be effective crystallization inhibitors. At higher bile salt concentrations, trihydroxy bile salts showed better inhibition compared to dihydroxy bile salts. These results highlight the importance of considering the composition of the test medium used to evaluate product performance, in particular in the context of evaluating crystallization kinetics

BPS-Saturated Walls in Supersymmetric Theories

Domain-wall solutions in four-dimensional supersymmetric field theories with distinct discrete vacuum states lead to the spontaneous breaking of supersymmetry, either completely or partially. We consider in detail the case when the domain walls are the BPS-saturated states, and 1/2 of supersymmetry is preserved. Several useful criteria that relate the preservation of 1/2 of supersymmetry on the domain walls to the central extension appearing in the N=1 superalgebras are established. We explain how the central extension can appear in N=1 supersymmetry and explicitly obtain the central charge in various models: the generalized Wess-Zumino models, and supersymmetric Yang-Mills theories with or without matter. The BPS-saturated domain walls satisfy the first-order differential equations which we call the creek equations, since they formally coincide with the (complexified) equations of motion of an analog high-viscosity fluid on a profile which is given by the superpotential of the original problem. Some possible applications are considered.Comment: Several equations are corrected, the discussion of the two-dimensional soliton in Section 6 is modified, references are updated and expande

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

Bile salts are endogenous surfactants present in the human gastrointestinal tract in the form of mixed micelles that also contain phospholipids. Due to the inevitable encounter of oral drug formulations with bile salts, it is important to understand the impact of bile salts on the crystallization tendency of poorly soluble compounds that form supersaturated solutions in vivo in order to maximize oral drug absorption. Although there has been an increasing number of studies focusing on the role of individual bile salts on drug crystallization, the effects of mixed micelles and biorelevant media composition on crystallization kinetics have only been studied to a limited extent. In this study, we evaluated the ability of binary and ternary bile salt combinations to maintain supersaturated aqueous solutions of telaprevir. Crystallization kinetics were also compared in more complex media that also contained the phospholipid, lecithin. These included fasted state simulated intestinal fluid (FaSSIF) (a widely used medium for formulation testing which contains a single bile salt, sodium taurocholate), and media that contained several endogenous bile salts. Finally, the combined effects of a polymer, hydroxypropyl methyl cellulose acetate succinate, and the testing media on crystallization kinetics were evaluated to provide insights into supersaturation formulation design. Solution bile salt composition was found to significantly influence crystallization kinetics. However, the presence of the polymer increased induction times sufficiently that differences between media were minimized. This study suggests that when evaluating the crystallization kinetics of systems with a propensity to undergo supersaturation in vivo, attention should be paid to selecting biorelevant media

Hazardous air pollutants and telomere length in the Sister Study

Background: Telomeres are vital for genomic integrity, and telomere length has been linked to many adverse health outcomes. Some hazardous air pollutants or air toxics increase oxidative stress and inflammation, two possible determinants of shortened telomere length. No studies have examined air toxic-Telomere length associations in a nonoccupational setting. Methods: This study included 731 Sister Study participants (enrolled 2003-2007) who were randomly selected to assess telomere length in baseline blood samples. Multiplex qPCR was used to determine telomere to single copy gene (T/S) ratios. Census tract concentration estimates of 29 air toxics from the 2005 National Air Toxics Assessment were linked to baseline residential addresses. Air toxics were classified into tertile-based categories of the exposure. Multivariable linear regression was used to estimate β coefficients and 95% confidence intervals (CIs) in single-pollutant models. Multipollutant groups were identified with regression trees. Results: The average T/S ratio was 1.24. Benzidine (T3 versus T1 β =-0.08; 95% CI =-0.14,-0.01) and 1,4-dioxane (T3 versus T1 β =-0.06; 95% CI =-0.13, 0.00) in particular, as well as carbon tetrachloride, chloroprene, ethylene dibromide, and propylene dichloride, were associated with shorter relative telomere length. Benzidine (P = 0.02) and 1,4-dioxane (P = 0.06) demonstrated some evidence of a monotonic trend. The regression tree identified age, BMI, physical activity, ethylene oxide, acrylonitrile, ethylidene dichloride, propylene dichloride, and styrene in multipollutant groups related to telomere length. Conclusions: In this first study of air toxics and telomere length in a nonoccupational setting, several air toxics, particularly 1,4-dioxane and benzidine, were associated with shorter relative telomere length

Characterizing the surge behaviour and associated ice-dammed lake evolution of the Kyagar Glacier in the Karakoram

Glacier surges are prevalent in the Karakoram and occasionally threaten local residents by inundating land and initiating mass movement events. The Kyagar Glacier is well known for its surge history, and in particular its frequent blocking of the downstream valley, leading to a series of high-magnitude glacial lake outburst floods (GLOFs). Although the surge dynamics of the Kyagar Glacier have been broadly described in the literature, there remains an extensive archive of remote sensing observations that have great potential for revealing specific surge characteristics and their relationship with historic lake outburst floods. In this study, we propose a new perspective on quantifying the surging process using successive digital elevation models (DEMs), which could be applied to other sites where glacier surges are known to occur. Advanced Spaceborne Thermal Emission and Reflection Radiometer DEMs, High Mountain Asia 8-meter DEMs, and the Shuttle Radar Topography Mission DEM were used to characterize surface elevation changes throughout the period from 2000 to 2021. We also used Landsat time series imagery to quantify glacier surface velocities and associated lake changes over the course of two surge events between 1989 and 2021. Using these datasets, we reconstruct the surging process of the Kyagar Glacier in unprecedented detail and find a clear signal of surface uplift over the lower glacier tongue, along with uniformly increasing velocities, associated with the period of surge initiation. Seasonal variations in surface flow are still evident throughout the surge phase, indicating the presence of water at the glacier bed. Surge activity of the Kyagar Glacier is strongly related to the development and drainage of the terminal ice-dammed lake, which itself is controlled by the drainage system beneath the glacier terminus