The Riddle of Ruth Bryan Owen

Her ancestors helped win America\u27s independence. As a child, she watched House debates with rapt attention, vowing eventually to return to her beloved Capitol building. She gazed out on millions of cheering faces during her father\u27s three presidential campaigns. Her uncle was a governor and vice-presidential nominee, her father the American Secretary of State. She ran the American Women\u27s War Relief Fund alongside future First Lady Lou Hoover and nursed dying Allied soldiers. After establishing herself as Florida\u27s leading female activist, she campaigned for the House of Representatives in 1928, promising to send her district\u27s most exemplary young citizens to Washington on an unparalleled civic pilgrimage

Peritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels

The importance of metabolism in macrophage function has been reported, but the in vivo relevance of the in vitro observations is still unclear. Here we show that macrophage metabolites are defined in a specific tissue context, and these metabolites are crucially linked to tissue-resident macrophage functions. We find the peritoneum to be rich in glutamate, a glutaminolysis-fuel that is exploited by peritoneal-resident macrophages to maintain respiratory burst during phagocytosis via enhancing mitochondrial complex-II metabolism. This niche-supported, inducible mitochondrial function is dependent on protein kinase C activity, and is required to fine-tune the cytokine responses that control inflammation. In addition, we find that peritoneal-resident macrophage mitochondria are recruited to phagosomes and produce mitochondrially derived reactive oxygen species, which are necessary for microbial killing. We propose that tissue-resident macrophages are metabolically poised in situ to protect and exploit their tissue-niche by utilising locally available fuels to implement specific metabolic programmes upon microbial sensing

The Upper Airway Response to Pollen is Enhanced by Exposure to Combustion Particulates: A Pilot Human Experimental Challenge Study.

Although human experimental studies have shown that gaseous pollutants enhance the inflammatory response to allergens, human data on whether combustion particulates enhance the inflammatory response to allergen are limited. Therefore, we conducted a human experimental study to investigate whether combustion particulates enhance the inflammatory response to aeroallergens. "Enhancement" refers to a greater-than-additive response when combustion particulates are delivered with allergen, compared with the responses when particulates and allergen are delivered alone. Eight subjects, five atopic and three nonatopic, participated in three randomized exposure-challenge sessions at least 2 weeks apart (i.e., clean air followed by allergen, particles followed by no allergen, or particles followed by allergen). Each session consisted of nasal exposure to combustion particles (target concentration of 1.0 mg/m$^3$) or clean air for 1 hr, followed 3 hr later by challenge with whole pollen grains or placebo. Nasal lavage was performed immediately before particle or clean air exposure, immediately after exposure, and 4, 18 and 42 hr after pollen challenge. Cell counts, differentials, and measurement of cytokines were performed on each nasal lavage. In atopic but not in nonatopic subjects, when allergen was preceded by particulates, there was a significant enhancement immediately after pollen challenge in nasal lavage leukocytes and neutrophils (29.7 X 10$^3$ cells/mL and 25.4 X 10$^3$ cells/mL, respectively). This represents a 143% and 130% enhancement, respectively. The enhanced response for interleukin-4 was 3.23 pg/mL (p = 0.06), a 395% enhancement. In atopic subjects there was evidence of an enhanced response when particulates, as compared to clean air, preceded the allergen challenge

Insulating and Conducting Phases of RbC60

Optical measurements were performed on thin films of Rb$_{x}$C$_{60}$, identified by X-ray diffraction as mostly $x=1$ material. The samples were subjected to various heat treatments, including quenching and slow cooling from 400K. The dramatic increase in the transmission of the quenched samples, and the relaxation towards the transmission observed in slow cooled samples provides direct evidence for the existence of a metastable insulating phase. Slow cooling results in a phase transition between two electrically conducting phases.Comment: Minor revisions. Submitted to PRB, RevTeX 3.0 file, 2 postscript figures included, ir_dop

Telemedical Direction to Optimize Resource Utilization in a Rural Emergency Medical Services System

Background: Telemedicine remains an underused tool in rural emergency medical servces (EMS) systems. Rural emergency medical technicians (EMT) and paramedics cite concerns that telemedicine could increase Advanced Life Support (ALS) transports, extend on-scene times, and face challenges related to connectivity as barriers to implementation. Our aim in this project was to implement a telemedicine system in a rural EMS setting and assess the impact of telemedicine on EMS management of patients with chest pain while evaluating some of the perceived barriers. Methods: This study was a mixed-methods, retrospective review of quality assurance data collected prior to and after implementation of a telemedicine program targeting patients with chest pain. We compared quantitative data from the 12-month pre-implementation phase to data from 15 months post-implementation. Patients were included if they had a chief complaint of chest pain or a 12-lead electrocardiogram had been obtained. The primary outcome was the rate of ALS transport before and after program implementation. Secondary outcomes included EMS call response times and EMS agency performance on quality improvement benchmarks. Qualitative data were also collected after each telemedicine encounter to evaluate paramedic/EMT and EMS physician perception of call quality. Results: The telemedicine pilot project was implemented in September 2020. Overall, there were 58 successful encounters. For this analysis, we included 38 patients in both the pre-implementation period (September 9, 2019–September 10, 2020) and the post-implementation period (September 11, 2020–December 5, 2021). Among this population, the ALS transport rate was 42% before and 45% after implementation (odds ratio 1.11; 95% confidence interval 0.45–2.76). The EMS median out-of-service times were 47 minutes before, and 33 minutes after (P = 0.07). Overall, 64% of paramedics/EMTs and 89% of EMS physicians rated the telemedicine call quality as “good.” Conclusion: In this rural EMS system, a telehealth platform was successfully used to connect paramedics/EMTs to board-certified EMS physicians over a 15-month period. Telemedicine use did not alter rates of ALS transports and did not increase on-scene time. The majority of paramedics/EMTs and EMS physicians rated the quality of the telemedicine connection as “good.

A genomic and evolutionary approach reveals non-genetic drug resistance in malaria

Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. Results: We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. Conclusions: We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0511-2) contains supplementary material, which is available to authorized users

A Preliminary Comparison of Pilots\u27 Weather Minimums and Actual Decision-Making

Adverse weather conditions remain a leading contributing factor in general aviation accidents. In compromising situations, such as severe weather, pilots continue to make decisions, which endanger themselves, passengers, and the aircraft. Although technology and training have lowered the risks associated with poor decision making by aviators, they are often still faced with scenarios requiring split second judgments. A countermeasure to these risks is the use of personal weather minimums by pilots. The purpose of this study was to examine pilot’s decision-making and performance, while flying an instrument approach, under extreme conditions of low visibility and ceiling as based on their stated personal minimums. A sample of 35 flight students with instrument ratings was recruited from a large university flight program located in the southeastern part of the United States. Participants were asked a series of pre-test questions, including their personal weather minimums, and then flew an ILS instrument approach on an Elite-1000 flight simulator at the subject university. The findings indicate approximately eighty percent of participants, on average, descended nearly two-hundred feet below their stated personal minimums before aborting the approach. Furthermore, forty percent of them also flew twenty-five feet below the federal requirement (200 feet above ground level) before aborting the approach. These results are pertinent to advance our understanding of the many different variables affecting pilot’s decision making. Understanding these outcomes will progress our initiatives to ensure safer air travel, while improving pilot’s competence and their passenger’s confidence

Basins of attraction on random topography

We investigate the consequences of fluid flowing on a continuous surface upon the geometric and statistical distribution of the flow. We find that the ability of a surface to collect water by its mere geometrical shape is proportional to the curvature of the contour line divided by the local slope. Consequently, rivers tend to lie in locations of high curvature and flat slopes. Gaussian surfaces are introduced as a model of random topography. For Gaussian surfaces the relation between convergence and slope is obtained analytically. The convergence of flow lines correlates positively with drainage area, so that lower slopes are associated with larger basins. As a consequence, we explain the observed relation between the local slope of a landscape and the area of the drainage basin geometrically. To some extent, the slope-area relation comes about not because of fluvial erosion of the landscape, but because of the way rivers choose their path. Our results are supported by numerically generated surfaces as well as by real landscapes