Effect of Growth Hormone (hGH) Replacement Therapy on Physical Work Capacity and Cardiac and Pulmonary Function in Patients with hGH Deficiency Acquired in Adulthood.

The effects of 6 months of replacement therapy with recombinant human GH (hGH) on physical work capacity and cardiac structure and function were investigated in 20 patients with hGH deficiency of adult onset in a double blind, placebo-controlled trial. The GH dose of 12.5 micrograms/kg BW was self-administered daily sc. Oxygen consumption (VO2), CO2 production, and ventilatory volumes were measured during exercise on a bicycle spiroergometer. M-Mode echocardiography was performed using standard techniques. The VO2 max data, expressed per kg BW (mL/min.kg BW) showed a significant increase from 23.2 +/- 2.4 to 30.0 +/- 2.3 (P < 0.01) in the hGH-treated group, whereas the VO2 max data, expressed per lean body mass (milliliters per min/kg lean body mass) did not change significantly in either group. Maximal O2 pulse (milliliters per beat) increased significantly from 15.2 +/- 5.6 to 19.6 +/- 3.3 mL/beat (P < 0.01), but remained constant in the placebo group. The maximal power output (watts +/- SE) increased significantly (P < 0.01) from 192.5 +/- 13.5 to 227.5 +/- 11.5 in the hGH-treated group, but remained constant in the placebo group. Cardiac structure (left ventricular posterior wall, interventricular septum thickness, left ventricular mass, left ventricular end-systolic dimension, and left ventricular end-diastolic dimension) as well as echocardiographically assessed cardiac function did not change significantly after 6 months of treatment in either group. We conclude that hGH replacement in hGH-deficient adults improves oxygen uptake and exercise capacity. These improvements in pulmonary parameters might be due to an increase in respiratory muscle strength and partly to the changes in muscle volume per se observed during hGH replacement therapy. Furthermore, an increased cardiac output might contribute to the improvement in exercise performance during hGH treatment. According to our data, hGH replacement therapy leads to an improvement of exercise capacity and maximal oxygen uptake, but has no significant effect on cardiac structure

Time-Resolved Tracking of Mutations Reveals Diverse Allele Dynamics during Escherichia coli Antimicrobial Adaptive Evolution to Single Drugs and Drug Pairs

Understanding the evolutionary processes that lead to antibiotic resistance can help to achieve better treatment strategies. Yet, little is known about the dynamics of the resistance alleles during adaptation. Here, we use population sequencing to monitor genetic changes in putative resistance loci at several time-points during adaptive evolution experiments involving five different antibiotic conditions. We monitor the mutational spectra in lineages evolved to be resistant to single antibiotics [amikacin (AMK), chloramphenicol (CHL), and ciprofloxacin (CIP)], as well as antibiotic combinations (AMK + CHL and CHL + CIP). We find that lineages evolved to antibiotic combinations exhibit different resistance allele dynamics compared with those of single-drug evolved lineages, especially for a drug pair with reciprocal collateral sensitivity. During adaptation, we observed interfering, superimposing and fixation allele dynamics. To further understand the selective forces driving specific allele dynamics, a subset of mutations were introduced into the ancestral wild type enabling differentiation between clonal interference and negative epistasis

Determinant of HIV-1 mutational escape from cytotoxic T lymphocytes.

CD8+ class I-restricted cytotoxic T lymphocytes (CTLs) usually incompletely suppress HIV-1 in vivo, and while analogous partial suppression induces antiretroviral drug-resistance mutations, epitope escape mutations are inconsistently observed. However, escape mutation depends on the net balance of selective pressure and mutational fitness costs, which are poorly understood and difficult to study in vivo. Here we used a controlled in vitro system to evaluate the ability of HIV-1 to escape from CTL clones, finding that virus replicating under selective pressure rapidly can develop phenotypic resistance associated with genotypic changes. Escape varied between clones recognizing the same Gag epitope or different Gag and RT epitopes, indicating the influence of the T cell receptor on pressure and fitness costs. Gag and RT escape mutations were monoclonal intra-epitope substitutions, indicating limitation by fitness constraints in structural proteins. In contrast, escape from Nef-specific CTL was more rapid and consistent, marked by a polyclonal mixture of epitope point mutations and upstream frameshifts. We conclude that incomplete viral suppression by CTL can result in rapid emergence of immune escape, but the likelihood is strongly determined by factors influencing the fitness costs of the particular epitope targeted and the ability of responding CTL to recognize specific epitope variants

NASA's Current Evidence and Hypothesis for the Visual Impairment and Intracranial Pressure Risk

While 40 years of human spaceflight exploration has reported visual decrement to a certain extent in a subgroup of astronauts, recent data suggests that there is indeed a subset of crewmembers that experience refraction changes (hyperoptic shift), cotton wool spot formation, choroidal fold development, papilledema, optic nerve sheath distention and/or posterior globe flattening with varying degrees of severity and permanence. Pre and postflight ocular measures have identified a potential risk of permanent visual changes as a result of microgravity exposure, which has been defined as the Visual Impairment and Intracranial Pressure risk (VIIP). The combination of symptoms are referred to as the VIIP syndrome. It is thought that the ocular structural and optic nerve changes are caused by events precipitated by the cephalad fluid shift crewmembers experience during long-duration spaceflight. Three important systems, ocular, cardiovascular, and central nervous, seem to be involved in the development of symptoms, but the etiology is still under speculation. It is believed that some crewmembers are more susceptible to these changes due to genetic/anatomical predisposition or lifestyle (fitness) related factors. Future research will focus on determining the etiology of the VIIP syndrome and development of mechanisms to mitigate the spaceflight risk

Cosmological stretching of perturbations on a cosmic string

We investigate the effects of cosmological expansion on the spectrum of small-scale structure on a cosmic string. We simulate the evolution of a string with two modes that differ in wavelength by one order of magnitude. Once the short mode is inside the horizon, we find that its physical amplitude remains unchanged, in spite of the fact that its comoving wavelength decreases as the longer mode enters the horizon. Thus the ratio of amplitude to wavelength for the short mode becomes larger than it would be in the absence of the long mode.Comment: 11 pages, 5 postscript figure

Tropospheric aqueous-phase chemistry: kinetics, mechanisms, and its coupling to a changing gas phase

[no abstract available

Understanding image-text relations and news values for multimodal news analysis

The analysis of news dissemination is of utmost importance since the credibility of information and the identification of disinformation and misinformation affect society as a whole. Given the large amounts of news data published daily on the Web, the empirical analysis of news with regard to research questions and the detection of problematic news content on the Web require computational methods that work at scale. Today's online news are typically disseminated in a multimodal form, including various presentation modalities such as text, image, audio, and video. Recent developments in multimodal machine learning now make it possible to capture basic “descriptive” relations between modalities–such as correspondences between words and phrases, on the one hand, and corresponding visual depictions of the verbally expressed information on the other. Although such advances have enabled tremendous progress in tasks like image captioning, text-to-image generation and visual question answering, in domains such as news dissemination, there is a need to go further. In this paper, we introduce a novel framework for the computational analysis of multimodal news. We motivate a set of more complex image-text relations as well as multimodal news values based on real examples of news reports and consider their realization by computational approaches. To this end, we provide (a) an overview of existing literature from semiotics where detailed proposals have been made for taxonomies covering diverse image-text relations generalisable to any domain; (b) an overview of computational work that derives models of image-text relations from data; and (c) an overview of a particular class of news-centric attributes developed in journalism studies called news values. The result is a novel framework for multimodal news analysis that closes existing gaps in previous work while maintaining and combining the strengths of those accounts. We assess and discuss the elements of the framework with real-world examples and use cases, setting out research directions at the intersection of multimodal learning, multimodal analytics and computational social sciences that can benefit from our approach