MEDICAL RESEARCH—The Program of the U. S. Public Health Service

Federal Government expenditures for medical research have increased apace in the last ten years. The increase in federal research funds has stimulated support from private sources; contributions from other than federal sources have doubled.More than half of medical research funds are being used by universities, hospitals, and other nonprofit institutions, and less than one-fourth by laboratories of the Federal Government.Grants-in-aid of research, fellowships and extended training are made on the advice of Advisory Councils made up of leaders in the various research fields. The previous record of research by staffs and faculties of institutions is taken into account. Special attention is given to unknown investigators and small projects.Noninterference with a scientist in the conduct of research is a basic principle of all grants. He may change the direction of his research to pursue promising leads without asking permission.Continuity of grants so that promising projects need not be abandoned at the end of a grant period is given special consideration.     

Habitat fragmentation and large-scale conservation: what do we know for sure?

We review the ecological effects of habitat fragmentation, comparing the theoretical approaches that have been taken to understanding it with the existing evidence from empirical studies. Theory has emphasized the spatial aspects of fragmentation and the role of dispersal among patches, and has generated interesting predictions such as a nonlinear relationship between the amount of remaining habitat and the probability of species persistence. However, while the few available large-scale empirical studies of fragmentation all tend to show that it has major effects, these documented effects tend to be relatively simple ones such as the degradation of habitat quality within fragments. There is good reason to be cautious of any claim that corridors or the spatial configuration of remaining habitat can compensate for the overall loss of habitat.
This is an invited Minireview on the occasion of the 50th anniversary of the Nordic Ecological Society Oikos.     

Lessons from Immune 1-3: what did we learn and what do we need to do in the future?

Sprague-Dawley rats were subjected to three 8-to-10 day space flights on the Space Shuttle. Housed in NASA's Animal Enclosure Modules, rats were flown to test the hypotheses that therapy with pegylated interleukin-2 or insulin-like growth factor-1 would ameliorate some of the effects of space flight on the immune system. As part of these experiments, we measured body and organ weights, blood cell differentials, plasma corticosterone, macrophage colony forming units, lymphocyte mitogenic, super-antigenic and interferon-gamma responses, bone marrow cell and peritoneal macrophage cytokine secretion and bone strength and mass. This paper compares some of the immunophysiological parameters of the control animals used in the Immune1-3 flight series and presents data from an animal infection model for use during space flight.     

Investigating physiological changes in the aerial parts of AM plants: what do we know and where should we be heading?

Research in the field of arbuscular mycorrhizal (AM) symbiosis has taken a giant leap in the past two decades, as demonstrated by the large amount of literature being published every year. Most of the research efforts have been put towards the understanding of the mechanisms of this symbiosis. However, there are still several unknowns on the systemic effects of the AM symbiosis, and our understanding of non-nutritional effects on the physiological changes occurring in the aerial parts of the host plant is yet quite limited. In this short note, I briefly address the question, if there are any changes in metabolic activities that are triggered by AM fungi, and assess the importance of such changes for mycorrhizal research and application.     

The asymmetry of existence: do we owe our existence to cold dark matter and the weak force?

A common theme throughout biology is homochirality, including its origin and especially implications. Homochirality has also intrigued scientists because of the hypothesis that life, as it currently exists, could not have occurred without it. In this review, we discuss several hypotheses regarding homochirality and their linkage to processes that range from subatomic in scale to processes that help define the structure of the universe. More importantly, this exploration begins with the knowledge that humans inhabit the universe in which there is an excess of normal matter over antimatter. It is a universe characterized by homochirality but is nonetheless contained in what is most easily described as a 3+1 dimensional spacetime wherein most laws of physics are invariant under spacetime transformations. This restriction on spacetime poses significant constraints on the processes that can be invoked to explain homochirality. However, in dealing with such restraints, including the total mass contained in the universe, the concepts of cold dark matter and dark energy can be incorporated into cosmological models with resultant behaviors and predictions very much in accord with the findings of the cosmic background surveys. Indeed, the introduction of cold dark matter and dark energy to solve problems relating to the mass found in the universe may provide a means for generating the needed asymmetry to allow homochirality to arise.     

Radioisotope stents for the prevention of restenosis: what did we learn from pre-clinical studies?

This article will discuss the lessons learned by using stents implanted with low activities of radioisotopes to prevent in-stent restenosis. A continuous low-dose rate radiation delivered by radioisotope stents has been shown to reduce the proliferative activity of smooth muscle cells and to inhibit neointimal growth. However, the radiation also delays endothelialization of the stents. Both the dose rate and the cumulative dose delivered by radioisotope stents appear to affect outcome. The neointima covering radioactive stents is characterized by a reduced cellularity, increased amounts of fibrin and extracellular matrix proteins. Aneurysm formation or excessive tissue destruction due to the radiation were not observed. Animals studies including up to 1 year follow-up periods suggest that beta-particle-radiation as well as gamma-radiation are effective in reducing neointimal hyperplasia. It is still unknown, however, which range of activities are needed and if a combination of radioisotopes, i.e. with short and long halflives, further reduce neotima formation over the long-term. An appropriate stent design for homogenous dose distribution around the stent may be important, i.e. articulations or large cell sizes may have disadvantages. Augmented neointima formation at the ends of radioactive stents, in particular when using beta-particle emitting stents, has been observed in animal models. Future studies will focus on the effects of increasing activity levels at the stent ends, optimal stent designs, alternative isotopes and different dosing strategies.     

Who are we when we are doing what we are doing?: the case for mindful embodiment in ethics case consultation

This paper explores the theory and practice of embodied epistemology or mindful embodiment in ethics case consultation. I argue that not only is this epistemology an ethical imperative to safeguard the integrity of this emerging profession, but that it has the potential to improve the quality of ethics consultation (EC). It also has implications for how ethics consultants are trained and how consultation services are organized. My viewpoint is informed by ethnographic research and by my experimental application of mindful embodiment to the development of an ethics consultation service. My argument proceeds in four phases. First I explore the notion of 'situatedness' in the bioethics literature, identifying gaps in the field's theories as they apply to EC. I then describe my theoretical approach to embodiment grounded in critical-interpretive medical anthropology and autoethnography. I use embodiment to refer to a moral epistemology grounded in the body, comprised of the interplay of physical, symbolic, intersubjective and political elements. Third, I describe how mindful embodiment can inform the role of the ethics consultant and the development of effective training techniques, vocabularies and processes for EC. I also discuss the benefits of this orientation, and the potential harms of ignoring the embodied dimensions of EC. My goals are to expose the fallacy of the 'theory-practice gap', to demonstrate how my own EC practice is deeply informed by this theoretical orientation, and to argue for a wider definition of what 'counts' as relevant theory for ethics consultation.     

Field Validity and Feasibility of Four Techniques for the Detection of Trichuris in Simians: A Model for Monitoring Drug Efficacy in Public Health?

Background

Soil-transmitted helminths, such as Trichuris trichiura, are of major concern in public health. Current efforts to control these helminth infections involve periodic mass treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring the drug efficacy will become indispensible. However, studies comparing detection techniques based on sensitivity, fecal egg counts (FEC), feasibility for mass diagnosis and drug efficacy estimates are scarce.

Methodology/Principal Findings

In the present study, the ether-based concentration, the Parasep Solvent Free (SF), the McMaster and the FLOTAC techniques were compared based on both validity and feasibility for the detection of Trichuris eggs in 100 fecal samples of nonhuman primates. In addition, the drug efficacy estimates of quantitative techniques was examined using a statistical simulation. Trichuris eggs were found in 47% of the samples. FLOTAC was the most sensitive technique (100%), followed by the Parasep SF (83.0% [95% confidence interval (CI): 82.4–83.6%]) and the ether-based concentration technique (76.6% [95% CI: 75.8–77.3%]). McMaster was the least sensitive (61.7% [95% CI: 60.7–62.6%]) and failed to detect low FEC. The quantitative comparison revealed a positive correlation between the four techniques (Rs = 0.85–0.93; p<0.0001). However, the ether-based concentration technique and the Parasep SF detected significantly fewer eggs than both the McMaster and the FLOTAC (p<0.0083). Overall, the McMaster was the most feasible technique (3.9 min/sample for preparing, reading and cleaning of the apparatus), followed by the ether-based concentration technique (7.7 min/sample) and the FLOTAC (9.8 min/sample). Parasep SF was the least feasible (17.7 min/sample). The simulation revealed that the sensitivity is less important for monitoring drug efficacy and that both FLOTAC and McMaster were reliable estimators.

Conclusions/Significance

The results of this study demonstrated that McMaster is a promising technique when making use of FEC to monitor drug efficacy in Trichuris.     

The molecular biology of recombination in Mycobacteria: what do we know and how can we use it?

Recombination is a ubiquitous genetic process which results in the exchange of DNA between two substrates. Homologous recombination occurs between DNA species with identical sequence whereas illegitimate recombination can occur between DNA with very little or no homology. Site-specific recombination is often used by temperate phages to stably integrate into bacterial chromosomes. Characterisation of the mechanisms of recombination in mycobacteria has mainly focussed on RecA-dependent homologous recombination and phage-directed site-specific recombination. In contrast the high frequency of illegitimate recombination in slow-growing mycobacteria has not been explained. The role of DNA repair in dormancy and infection have not yet been fully established, but early work suggests that RecA-mediated pathways are not required for virulence. All three recombination mechanisms have been utilised in developing genetic techniques for the analysis of the biology and pathogenesis of mycobacteria. A recently developed method for studying essential genes will generate further insights into the biology of these important organisms.     

U.S. racial and ethnic relations in the twenty-first century: are old divisions prevailing?

In this response to Valdez and Golash-Boza’s article, U.S. Racial and Ethnic Relations in the twenty-first century, I commend the authors for raising critical issues about the traditional lack of integration of race and ethnicity paradigms. However, I argue that, in an effort to make their claim about the distinction between the ethnicity and race paradigms, they end up oversimplifying some of the literature and overlook the ways in which race and ethnicity scholarship from the twenty-first century has made important advances towards paradigm integration. In my response I provide an alternate reading of some of the literature that the authors critique, focusing on the Mexican middle-class case. I then highlight scholars who are working towards race–ethnicity integration, moving past old paradigm divides. I conclude my response by introducing the concept of the “ethnoracial core”, which I believe moves us in the direction that Valdez and Golash-Boza are proposing.     

Molecular polymorphism in Drosophila melanogaster and D. simulans: what have we learned from recent studies?

We present a review of recent studies of molecular polymorphism in Drosophila melanogaster and D. simulans. The availability of African and non-African samples for these species makes it possible to compare microsatellite and DNA sequence polymorphism between these species, both inside and outside their native regions. There are four main results: (i) variability is larger in African populations; (ii) variation is usually higher on the autosomes, except for African D. melanogaster; (iii) DNA sequence variation is higher on D. simulans than on D. melanogaster autosomes; (iv) the ratio of replacement to silent polymorphisms is higher for D. melanogaster autosomal loci. We summarize the main hypotheses put forward to explain these results.     

Radiation-induced lung injury — what do we know in the era of modern radiotherapy?

Radiation-induced lung injury (RILI) that is usually divided into an early radiation-induced pneumonitis (RIP) and late chronic radiation-induced lung fibrosis (RILF) remains a clinically significant toxicity in radiation oncology. Thus, a thorough understanding of underlying molecular mechanisms and risk factors is crucial. This review, focused on patients treated with modern radiotherapy (RT) techniques, describes the different clinical presentations of RIP, with most typical imaging findings and usefulness of pulmonary function tests and laboratory assessment in differential diagnosis. The most critical patient- and treatment-related predictors are summarized and discussed — age and sex, comorbidities, tumour characteristics, concomitant treatment, and RT-plan parameters. The conventional grading scales and contemporary approach to quantitative assessment (radiomics, CT density changes) is described as well as treatment methods.     

Invasive trees and shrubs: where do they come from and what we should expect in the future?

The global database of invasive trees and shrubs has been updated, resulting in a total of 751 species (434 trees and 317 shrubs) from 90 families (Rejmánek and Richardson 2013 Divers Distrib 19:1093–1094). This database is used to assess major trends in human-assisted exchanges of dendrofloras among 15 major geographical regions. Areas most invaded by non-native trees are Pacific Islands (136 species), Southern Africa (118), Australia (116), and North America (114). Areas most invaded by non-native shrubs are North America (98), Australia (87), Pacific Islands (71), and Europe (61). The most important sources of invasive trees are Asia (122–146 species, depending on how many Eurasian species are considered to have been introduced only from Europe), Australia (81), and South America (81). The most important sources of invasive shrubs are Asia (103–118), Europe (68), and South America (54). Mean number of native geographical regions for invasive trees is 1.64, while the mean number of invaded regions by trees is 2.51. The difference is smaller for shrubs: 1.60 versus 2.11. Asia is the major source of invasive Rosaceae shrubs, as well as invasive Arecaceae and Oleaceae species. South America and Australia are major sources of invasive Fabaceae trees. North America and Europe are major sources of invasive Pinaceae. Most of the invasive Salicaceae are of Eurasian origin. The identified trends will very likely continue in this century. Because of increasing interactions with many states in Asia, even more invasive woody species will be introduced from this part of the world.     

Meteorite or gemstone? Dreaming as one end of a continuum of functioning: Implications for research and for the use of dreams in therapy and self-knowledge.

Is a dream a meteorite—a bit of material arriving from a distant place that needs to be carefully analyzed to give us knowledge about that place (outside or inside us)? Is it a strange text which has come to us in a foreign language, that needs to be translated into our own? This “meteorite view” is held by some religious and spiritual persons, by many orthodox psychoanalysts and other therapists, and implicitly by many researchers. They all see the dream as something alien, something totally different from our ordinary mental functioning. This paper presents a great deal of research favoring an alternate view—that the dream is an earth-stone, not an alien stone. It may be impressive and beautiful (gemstone), but it's still an earth-stone. The dream is part of our mental functioning. It is one end of a continuum, running from focused waking thought, through looser thought, fantasy, daydreaming, reverie and dreaming. We review reasons why dreams are often considered “totally different”: they're perceptual, not conceptual; they're bizarre; they are “so real”; they're so easily forgotten; they're involuntary; they occur in REM sleep—a totally different state. We demonstrate that none of these reasons are persuasive. In each sense, there is overlap between dreams and other forms of functioning. The continuum view leads to different kinds of research and a different style of dreamwork. It also helps answer questions the field has long struggled with including: Should we study “a dream” or “dreaming”? Are dreams meaningful or meaningless? (PsycINFO Database Record (c) 2010 APA, all rights reserved)