A life in progress: motion and emotion in the autobiography of Robert M. La Follette

This article is a study of a La Follette’s Autobiography, the autobiography of the leading Wisconsin progressive Robert M. La Follette, which was published serially in 1911 and, in book form, in 1913. Rather than focusing, as have other historians, on which parts of La Follette’s account are accurate and can therefore be trusted, it explains instead why and how this major autobiography was conceived and written. The article shows that the autobiography was the product of a sustained, complex, and often fraught series of collaborations among La Follette’s family, friends, and political allies, and in the process illuminates the importance of affective ties as well as political ambition and commitment in bringing the project to fruition. In the world of progressive reform, it argues, personal and political experiences were inseparable

The dose of hemodialysis and patient mortality

The dose of hemodialysis and patient mortality. The relationship between the delivered dose of hemodialysis and patient mortality remains somewhat controversial. Several observational studies have shown improved patient survival with higher levels of delivered dialysis dose. However, several other unmeasured variables, changes in patient mix or medical management may have impacted on this reported difference in mortality. The current study of a U.S. national sample of 2,311 patients from 347 dialysis units estimates the relationship of delivered hemodialysis dose to mortality, with a statistical adjustment for an extensive list of comorbidity/risk factors. Additionally this study investigated the existence of a dose beyond which more dialysis does not appear to lower mortality. We estimated patient survival using proportional hazards regression techniques, adjusting for 21 patient comorbidity/risk factors with stratification for nine Census regions. The patient sample was 2,311 Medicare hemodialysis patients treated with bicarbonate dialysate as of 12/31/90 who had end-stage renal disease for at least one year. Patient follow-up ranged between 1.5 and 2.4 years. The measurement of delivered therapy was based on two alternative measures of intradialytic urea reduction, the urea reduction ratio (URR) and Kt/V (with adjustment for urea generation and ultrafiltration). Hemodialysis patient mortality showed a strong and robust inverse correlation with delivered hemodialysis dose whether measured by Kt/V or by URR. Mortality risk was lower by 7% (P = 0.001) with each 0.1 higher level of delivered Kt/V. (Expressed in terms of URR, mortality was lower by 11% with each 5 percentage point higher URR; P = 0.001). Above a URR of 70% or a Kt/V of 1.3 these data did not provide statistical evidence of further reductions in mortality. In conclusion, the delivered dose of hemodialysis therapy is an important predictor of patient mortality. In a population of dialysis patients with a very high mortality rate, it appears that increasing the level of delivered therapy offers a practical and efficient means of lowering the mortality rate. The level of hemodialysis dose measured by URR or Kt/V beyond which the mortality rate does not continue to decrease, though not well defined with this study, appears to be above current levels of typical treatment of hemodialysis patients in the U.S

A One Health overview, facilitating advances in comparative medicine and translational research.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman

Altered Gene Expression in Early Atherosclerosis Is Blocked by Low Level Apolipoprotein E

BACKGROUND: Mice deficient in apolipoprotein E (apoE(-/-)) develop atherosclerosis. The possible linkage between expression of adhesion molecules/cofactors and atherosclerosis was probed at the level of mRNA and protein expression. The hypothesis of a linkage between changes of adhesion molecules/cofactors and atherosclerosis was tested further by suppression of aortic lesion formation in apoE(-/-) mice by expression of very low levels of transgenic apolipoprotein E. METHODOLOGY/PRINCIPAL FINDINGS: We show that at 8.5 months of age, the apoE(-/-) mice display elevated expression of mRNA for LFA-1, MAC-1, VCAM-1, ICAM-1, and for CD44, as well as MCP-1, cathepsin B, and COX-2 (but not that for eNOS) in atherosclerotic aortic arches. At earlier age, (10-13 week old) apoE(-/-) mice already display elevated expression of mRNA of CD44, LFA-1, MAC-1, VCAM-1, ICAM-1, cathepsin, and of COX-2 in lesioned aortic arches. Expressing very low levels of transgenic apolipoprotein E suppresses both aortic lesions and the expression of mRNA of LFA-1, VCAM-1, MCP-1, cathepsin B, and of ICAM-1 in ApoE(-/-) mice. We tested at the level of protein, the observations obtained for mRNA expression. CD11a (a component of LFA-1), VCAM-1 and cathepsin B expression was found to be elevated in apoE(-/-) aortas at 8-9 months; low level expression of transgenic apolipoprotein E rectifies these changes. CONCLUSIONS/SIGNIFICANCE: Atherosclerotic lesions in apoE(-/-) mice are detected as early as 4 weeks of age. Expression of low levels of apoE is shown to be both atheroprotective and to suppress these changes in key adhesion and inflammatory molecules observed in early atherosclerotic lesions

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base

Planck 2015 results. XVI. Isotropy and statistics of the CMB

We test the statistical isotropy and Gaussianity of the cosmic microwave background (CMB) anisotropies using observations made by the Planck satellite. Our results are based mainly on the full Planck mission for temperature, but also include some polarization measurements. In particular, we consider the CMB anisotropy maps derived from the multi-frequency Planck data by several component-separation methods. For the temperature anisotropies, we find excellent agreement between results based on these sky maps over both a very large fraction of the sky and a broad range of angular scales, establishing that potential foreground residuals do not affect our studies. Tests of skewness, kurtosis, multi-normality, N-point functions, and Minkowski functionals indicate consistency with Gaussianity, while a power deficit at large angular scales is manifested in several ways, for example low map variance. The results of a peak statistics analysis are consistent with the expectations of a Gaussian random field. The “Cold Spot” is detected with several methods, including map kurtosis, peak statistics, and mean temperature profile. We thoroughly probe the large-scale dipolar power asymmetry, detecting it with several independent tests, and address the subject of a posteriori correction. Tests of directionality suggest the presence of angular clustering from large to small scales, but at a significance that is dependent on the details of the approach. We perform the first examination of polarization data, finding the morphology of stacked peaks to be consistent with the expectations of statistically isotropic simulations. Where they overlap, these results are consistent with the Planck 2013 analysis based on the nominal mission data and provide our most thorough view of the statistics of the CMB fluctuations to date

Why did the apple fall? A new model to explain Einstein's gravity

© 2016 IOP Publishing Ltd. Newton described gravity as an attractive force between two masses but Einstein's General Theory of Relativity provides a very different explanation. Implicit in Einstein's theory is the idea that gravitational effects are the result of a distortion in the shape of space-time. Despite its elegance, Einstein's concept of gravity is rarely encountered outside of an advanced physics course as it is often considered to be too complex and too mathematical. This paper describes a new conceptual and quantitative model of gravity based on General Relativity at a level most science students should be able to understand. The model illustrates geodesics using analogies with paths of navigation on the surface of the Earth. This is extended to space and time maps incorporating the time warping effects of General Relativity. Using basic geometry, the geodesic path of a falling object near the surface of the Earth is found. From this the acceleration of an object in free fall is calculated. The model presented in this paper can answer the question, 'Why do things fall?' without resorting to Newton's gravitational force