Sequencing, Acoustic Separation, and 3-D Negotiation of Complex Barriers: Charlene Barshefsky and IP Rights in China

Taking the perspective of the lead U.S. negotiator, Charlene Barshefsky, this article details and analyzes the negotiations that took place in the mid-1990s between the United States and the People\u27s Republic of China over intellectual property rights (IPR). Employing a negotiation analytic methodology, Charlene Barshefsky\u27s actions are interpreted to suggest a number of promising approaches to managing the daunting complexities of trade and other negotiations: recognizing the multiparty aspects of apparently bilateral dealings and capturing them in a deal diagram; carefully assessing barriers to agreement; sequencing to build a winning coalition and overcome potentially blocking ones; acoustic separation of issueframes; and, most broadly, changing the game advantageously relative to a purely tactical orientation at the table through 3-D actions away from the table

Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release

A Pilot Study Comparing Opaque, Weighted Bottles with Conventional, Clear Bottles for Infant Feeding

It is hypothesized that the visual and weight cues afforded by bottle-feeding may lead mothers to overfeed in response to the amount of liquid in the bottle. The aim of the present pilot study was to test this hypothesis by comparing mothers\u27 sensitivity and responsiveness to infant cues and infants\u27 intakes when mothers use opaque, weighted bottles (that remove visual and weight cues) compared to conventional, clear bottles to feed their infants. We also tested the hypothesis that mothers\u27 pressuring feeding style would moderate the effect of bottle type. Formula-feeding dyads (N = 25) visited our laboratory on two separate days. Mothers fed their infants from a clear bottle one day and an opaque, weighted bottle on the other; bottle-order was counterbalanced across the two days. Infant intake was assessed by weighing each bottle before and after the feeding. Maternal sensitivity and responsiveness to infant cues was objectively assessed using the Nursing Child Assessment Feeding Scale. Mothers were significantly more responsive to infant cues when they used opaque compared to clear bottles (p = .04). There was also a trend for infants to consume significantly less formula when fed from opaque compared to clear bottles (p = .08). Mothers\u27 pressuring feeding style moderated the effect of bottle type on maternal responsiveness to infant cues (p = .02) and infant intake (p = .03). Specifically, mothers who reported higher levels of pressuring feeding were significantly more responsive to their infants\u27 cues (p = .02) and fed their infants significantly less formula when using opaque versus clear bottles (p = .01); no differences were seen for mothers who reported lower levels of pressuring feeding. This study highlights a simple, yet effective intervention for improving the bottle-feeding practices of mothers who have pressuring feeding styles

Using pH abnormalities in diseased skin to trigger and target topical therapy

Abstract Purpose: The pH discrepancy between healthy and atopic dermatitis skin was identified as a site specific trigger for delivering hydrocortisone from microcapsules. Methods: Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed and preliminary stability data was determined. Results: Drug release from microparticles was pH-dependent though the particles produced by spray drying also gave significant non-pH dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In-vitro studies showed 4 to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5. Conclusions: Permeation studies showed that the oil-in-oil generated particles deliver essentially no drug at normal (intact) skin pH (5.0 – 5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin

Small domain estimation of census coverage: A case study in Bayesian analysis of complex survey data

Many countries conduct a full census survey to report official population statistics. As no census survey ever achieves 100 per cent response rate, a post-enumeration survey (PES) is usually conducted and analysed to assess census coverage and produce official population estimates by geographic area and demographic attributes. Considering the usually small size of PES, direct estimation at the desired level of disaggregation is not feasible. Design-based estimation with sampling weight adjustment is a commonly used method but is difficult to implement when survey non-response patterns cannot be fully documented and population benchmarks are not available. We overcome these limitations with a fully model-based Bayesian approach applied to the New Zealand PES. Although theory for the Bayesian treatment of complex surveys has been described, published applications of individual level Bayesian models for complex survey data remain scarce. We provide such an application through a case study of the 2018 census and PES surveys. We implement a multilevel model that accounts for the complex design of PES. We then illustrate how mixed posterior predictive checking and cross-validation can assist with model building and model selection. Finally, we discuss potential methodological improvements to the model and potential solutions to mitigate dependence between the two surveys.Comment: 35 pages, 5 figures This is an author version of a paper accepted for publication in the Journal of Official Statistics. Once published by the Journal of Official Statistics use the Journal citation. This version includes supplementary material and corrected version of Figure

“We can all just get on a bus and go” : Rethinking independent mobility in the context of the universal provision of free bus travel to young Londoners

This paper uses qualitative data from interviews with 118 young Londoners (age 12-18) to examine how the universal provision of free bus travel has affected young people’s independent mobility. Drawing on Sen’s ‘capabilities approach’, we argue that free bus travel enhanced young Londoners’ capability to shape their daily mobility, both directly by increasing financial access and indirectly by facilitating the acquisition of the necessary skills, travelling companions and confidence. These capabilities in turn extended both opportunity freedoms (e.g. facilitating non-“necessary” recreational and social trips) and process freedoms (e.g. feeling more independent by decreasing reliance on parents). Moreover, the universal nature of the entitlement rendered buses a socially inclusive way for groups to travel and spend time together, thereby enhancing group-level capabilities. We believe this attention to individual and group capabilities for self-determination provides the basis for a broader and more child-centred view of ‘independent mobility’ than the typical research focus upon ‘travelling without an adult’ and acquiring parental permissions.Peer reviewe

Closing the Coverage Gaps: Reducing Health Insurance Disparities in Massachusetts

Massachusetts has been exemplary in developing health insurance coverage policies to cover its residents. By 2019, the state's uninsurance rate was 3.0 percent, the lowest rate in the nation, representing about 204,000 uninsured residents. While the state's overall uninsured rate at a given point in time is low, more than twice as many people - 503,000, or 7.3 percent of the population - experienced a gap in coverage over the previous twelve months. And importantly, not all groups benefit equally. People who are Black or Hispanic, or who have lower incomes, experience significantly higher rates of uninsurance than the state population overall. As a result, these groups are more likely to face access barriers and financial insecurity associated with being uninsured.The purpose of this report is to begin charting a course toward closing the coverage gaps in Massachusetts, with a particular focus on creating a more racially and ethnically equitable system of coverage. The report and accompanying infographics describe the people in Massachusetts without health insurance and the barriers to coverage they face, including affordability, administrative complexity, and immigration, language, and cultural barriers. It then proposes a menu of policy options that address the specific circumstances in Massachusetts. The proposed options are meant to inform a statewide conversation about the best approaches to closing the remaining coverage gaps in Massachusetts and removing structural barriers that result in racial and ethnic disparities in health insurance coverage

CO in Protostars (COPS): HerschelHerschel-SPIRE Spectroscopy of Embedded Protostars

We present full spectral scans from 200-670$\mu$m of 26 Class 0+I protostellar sources, obtained with $Herschel$-SPIRE, as part of the "COPS-SPIRE" Open Time program, complementary to the DIGIT and WISH Key programs. Based on our nearly continuous, line-free spectra from 200-670 $\mu$m, the calculated bolometric luminosities ($L_{\rm bol}$) increase by 50% on average, and the bolometric temperatures ($T_{\rm bol}$) decrease by 10% on average, in comparison with the measurements without Herschel. Fifteen protostars have the same Class using $T_{\rm bol}$ and $L_{\rm bol}$/$L_{\rm submm}$. We identify rotational transitions of CO lines from J=4-3 to J=13-12, along with emission lines of $^{13}$CO, HCO$^+$, H$_{2}$O, and [CI]. The ratios of $^{12}$CO to $^{13}$CO indicate that $^{12}$CO emission remains optically thick for $J_{\rm up}$ < 13. We fit up to four components of temperature from the rotational diagram with flexible break points to separate the components. The distribution of rotational temperatures shows a primary population around 100 K with a secondary population at $\sim$350 K. We quantify the correlations of each line pair found in our dataset, and find the strength of correlation of CO lines decreases as the difference between $J$-level between two CO lines increases. The multiple origins of CO emission previously revealed by velocity-resolved profiles are consistent with this smooth distribution if each physical component contributes to a wide range of CO lines with significant overlap in the CO ladder. We investigate the spatial extent of CO emission and find that the morphology is more centrally peaked and less bipolar at high-$J$ lines. We find the CO emission observed with SPIRE related to outflows, which consists two components, the entrained gas and shocked gas, as revealed by our rotational diagram analysis as well as the studies with velocity-resolved CO emission.Comment: 50 pages, 18 figures, accepted to ApJS. Revised for Table 6 and Figure

The kinetochore-microtubule coupling machinery is repurposed in sensory nervous system morphogenesis

Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule&nbsp;coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C.&nbsp;elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis

Prefrontal Corticotropin-Releasing Factor (CRF) Neurons Act Locally to Modulate Frontostriatal Cognition and Circuit Function.

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction