Cued repetition of self-directed behaviors in macaques (Macaca nemestrina)

Two macaques were trained to perform three self-directed behaviors on signal, and to repeat behaviors after a ‘repeat’ signal. The cognitive processes underlying the monkeys’ repeat performance were evaluated using multiple repetitions of the repeat signal, extended delay periods between target behavior and repeat signal, and by transferring the repeat signal to novel behaviors. The monkeys appear to have used representations of their own past behaviors as a basis for repetition performance, but they mostly failed to correctly repeat target behaviors after extended delays and during transfer tasks. Implications for episodic memory abilities are discussed

Inhaled alpha 1 -proteinase inhibitor therapy in patients with cystic fibrosis

Inhaled alpha1-proteinase inhibitor (PI) is known to reduce neutrophil elastase burden in some patients with CF. This phase 2a study was designed to test inhaled Alpha-1 HC, a new aerosolized alpha1-PI formulation, in CF patients

Treatment of Bladder Stones in Adults and Children : A Systematic Review and Meta-analysis on Behalf of the European Association of Urology Urolithiasis Guideline Panel

Peer reviewedPostprin

Stability Walls in Heterotic Theories

We study the sub-structure of the heterotic Kahler moduli space due to the presence of non-Abelian internal gauge fields from the perspective of the four-dimensional effective theory. Internal gauge fields can be supersymmetric in some regions of the Kahler moduli space but break supersymmetry in others. In the context of the four-dimensional theory, we investigate what happens when the Kahler moduli are changed from the supersymmetric to the non-supersymmetric region. Our results provide a low-energy description of supersymmetry breaking by internal gauge fields as well as a physical picture for the mathematical notion of bundle stability. Specifically, we find that at the transition between the two regions an additional anomalous U(1) symmetry appears under which some of the states in the low-energy theory acquire charges. We compute the associated D-term contribution to the four-dimensional potential which contains a Kahler-moduli dependent Fayet-Iliopoulos term and contributions from the charged states. We show that this D-term correctly reproduces the expected physics. Several mathematical conclusions concerning vector bundle stability are drawn from our arguments. We also discuss possible physical applications of our results to heterotic model building and moduli stabilization.Comment: 37 pages, 4 figure

Obstructions to the Existence of Sasaki-Einstein Metrics

We describe two simple obstructions to the existence of Ricci-flat Kahler cone metrics on isolated Gorenstein singularities or, equivalently, to the existence of Sasaki-Einstein metrics on the links of these singularities. In particular, this also leads to new obstructions for Kahler-Einstein metrics on Fano orbifolds. We present several families of hypersurface singularities that are obstructed, including 3-fold and 4-fold singularities of ADE type that have been studied previously in the physics literature. We show that the AdS/CFT dual of one obstruction is that the R-charge of a gauge invariant chiral primary operator violates the unitarity bound.Comment: 35 pages, 1 figure; references and a footnote adde

Stakeholder Theory and Marketing: Moving from a Firm-Centric to a Societal Perspective

This essay is inspired by the ideas and research examined in the special section on “Stakeholder Marketing” of the Journal of Public Policy & Marketing in 2010. The authors argue that stakeholder marketing is slowly coalescing with the broader thinking that has occurred in the stakeholder management and ethics literature streams during the past quarter century. However, the predominant view of stakeholders that many marketers advocate is still primarily pragmatic and company centric. The position advanced herein is that stronger forms of stakeholder marketing that reflect more normative, macro/societal, and network-focused orientations are necessary. The authors briefly explain and justify these characteristics in the context of the growing “prosociety” and “proenvironment” perspectives—orientations that are also in keeping with the public policy focus of this journal. Under the “hard form” of stakeholder theory, which the authors endorse, marketing managers must realize that serving stakeholders sometimes requires sacrificing maximum profits to mitigate outcomes that would inflict major damage on other stakeholders, especially society

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Correlates of prior HIV testing and schistosomiasis treatment: Baseline survey findings from the “creating demand for fishermen’s schistosomiasis HIV services” (FISH) cluster-randomized trial in Mangochi, Malawi

Background: Fishing exposes fishermen to schistosomiasis-infested fresh water and concurrently through precarious livelihoods to risky sexual behaviour, rendering these two infections occupational hazards for fishermen. This study aimed to characterize the knowledge of the two conditions to obtain necessary data for a subsequent cluster randomized trial designed to investigate demand creation strategies for joint HIV-schistosomiasis service provision in fishing villages on the shores of southern Lake Malawi. Methods: Enumeration of all resident fishermen in 45 clusters (fishing communities) was carried out between November 2019 and February 2020. In a baseline survey, fishermen reported their knowledge, attitudes and practices in the uptake of HIV and schistosomiasis services. Knowledge of HIV status and previous receipt of praziquantel were modelled using random effects binomial regression, accounting for clustering. Prevalence of willingness to attend a beach clinic was computed. Results: A total of 6,297 fishermen were surveyed from the 45 clusters with harmonic mean number of fishermen per cluster of 112 (95% CI: 97; 134). The mean age was 31.7y (SD: 11.9) and nearly 40% (2,474/6,297) could not read or write. Overall, 1,334/6,293 (21.2%) had never tested for HIV, with 64.4% (3,191/4,956) having tested in the last 12 months, and 5.9% (373/6290) taking antiretroviral therapy (ART). In adjusted analyses, being able to read and write (adjusted risk ratio [aRR: 1.91, 95% CI: 1.59–2.29, p<0.001); previous use of praziquantel (aRR: 2.00,95% CI: 1.73–2.30, p<0.001); knowing a relative or friend who died of HIV (aRR: 1.54,95% CI: 1.33–1.79, p<0.001); and being on ART (aRR: 12.93, 95% CI: 6.25–32.93, p<0.001) were associated with increased likelihood of ever testing for HIV. Only 40% (1,733/4,465) had received praziquantel in the last 12 months. Every additional year of age was associated with 1% decreased likelihood of having taken praziquantel in the last 12 months (aRR: 0.99, 95% CI: 0.98–0.99, p<0.001). However, recent HIV testing increased the likelihood of taking praziquantel by over 2-fold (aRR 2.24, 95% CI: 1.93–2.62, p<0.001). Willingness to attend a mobile beach clinic offering integrated HIV and schistosomiasis services was extremely high at 99.0% (6,224/6,284). Conclusion: In a setting with an underlying high prevalence of both HIV and schistosomiasis, we found low knowledge of HIV status and low utilization of free schistosomiasis treatment. Among fishermen who accessed HIV services, there was a very high likelihood of taking praziquantel suggesting that integrated service delivery may lead to good coverage. Trial registration: This trial is registered in the ISRCTN registry: ISRCTN14354324; date of registration: 05 October 2020

A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: a comparative study of human psychophysics and rat behaviour

Background: Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents. New method: We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured. Results: Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: −11.3 °C to −11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours. Comparison: Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients. Conclusion: Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain