LeRoy Walters's Legacy of Bioethics in Genetics and Biotechnology Policy.

LeRoy Walters was at the center of public debate about emerging biological technologies, even as "biotechnology" began to take root. He chaired advisory panels on human gene therapy, the human genome project, and patenting DNA for the congressional Office of Technology Assessment. He chaired the subcommittee on Human Gene Therapy for NIH's Recombinant DNA Advisory Committee. He was also a regular advisor to Congress, the executive branch, and academics concerned about policy governing emerging biotechnologies. In large part due to Prof. Walters, the Kennedy Institute of Ethics was one of the primary sources of talent in bioethics, including staff who populated policy and science agencies dealing with reproductive and genetic technologies, such as NIH and OTA. His legacy lies not only in his writings, but in those people, documents, and discussions that guided biotechnology policy in the United States for three decades.

Enhancing the diversity of breeding invertebrates within field margins of intensively managed grassland: Effects of alternative management practices.

Severe declines in biodiversity have been well documented for many taxonomic groups due to intensification of agricultural practices. Establishment and appropriate management of arable field margins can improve the diversity and abundance of invertebrate groups; however, there is much less research on field margins within grassland systems. Three grassland field margin treatments (fencing off the existing vegetation "fenced"; fencing with rotavation and natural regeneration "rotavated" and; fencing with rotavation and seeding "seeded") were compared to a grazed control in the adjacent intensively managed pasture. Invertebrates were sampled using emergence traps to investigate species breeding and overwintering within the margins. Using a manipulation experiment, we tested whether the removal of grazing pressure and nutrient inputs would increase the abundance and richness of breeding invertebrates within grassland field margins. We also tested whether field margin establishment treatments, with their different vegetation communities, would change the abundance and richness of breeding invertebrates in the field margins. Exclusion of grazing and nutrient inputs led to increased abundance and richness in nearly all invertebrate groups that we sampled. However, there were more complex effects of field margin establishment treatment on the abundance and richness of invertebrate taxa. Each of the three establishment treatments supported a distinct invertebrate community. The removal of grazing from grassland field margins provided a greater range of overwintering/breeding habitat for invertebrates. We demonstrate the capacity of field margin establishment to increase the abundance and richness in nearly all invertebrate groups in study plots that were located on previously more depauperate areas of intensively managed grassland. These results from grassland field margins provide evidence to support practical actions that can inform Greening (Pillar 1) and agri-environment measures (Pillar 2) of the Common Agricultural Policy (CAP). Before implementing specific management regimes, the conservation aims of agri-environment measures should be clarified by defining the target species or taxonomic groups.

Species-area relationships are modulated by trophic rank, habitat affinity, and dispersal ability.

In the face of ongoing habitat fragmentation, species-area relationships (SARs) have gained renewed interest and are increasingly used to set conservation priorities. An important question is how large habitat areas need to be to optimize biodiversity conservation. The relationship between area and species richness is explained by colonization-extinction dynamics, whereby smaller sites harbor smaller populations, which are more prone to extinction than the larger populations sustained by larger sites. These colonization-extinction dynamics are predicted to vary with trophic rank, habitat affinity, and dispersal ability of the species. However, empirical evidence for the effect of these species characteristics on SARs remains inconclusive. In this study we used carabid beetle data from 58 calcareous grassland sites to investigate how calcareous grassland area affects species richness and activity density for species differing in trophic rank, habitat affinity, and dispersal ability. In addition, we investigated how SARs are affected by the availability of additional calcareous grassland in the surrounding landscape. Beetle species richness and activity density increased with calcareous grassland area for zoophagous species that are specialists for dry grasslands and, to a lesser extent, for zoophagous habitat generalists. Phytophagous species and zoophagous forest and wet-grassland specialists were not affected by calcareous grassland area. The dependence of species on large single sites increased with decreasing dispersal ability for species already vulnerable to calcareous grassland area. Additional calcareous grassland in the landscape had a positive effect on local species richness of both dry-grassland specialists and generalists, but this effect was restricted to a few hundred meters. Our results demonstrate that SARs are affected by trophic rank, habitat affinity, and dispersal ability. These species characteristics do not operate independently, but should be viewed in concert. In addition, species' responses depend on the landscape context. Our study suggests that the impact of habitat area on trophic interactions may be larger than previously anticipated. In small habitat fragments surrounded by a hostile matrix, food chains may be strongly disrupted. This highlights the need to conserve continuous calcareous grassland patches of at least several hectares in size.

Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial.

The only causative treatment for IgE-mediated allergies is allergen-specific immunotherapy. However, fewer than 5% of allergy patients receive immunotherapy because of its long duration and risk of allergic side effects. We aimed at enhancing s.c. immunotherapy by direct administration of allergen into s.c. lymph nodes. The objective was to evaluate safety and efficacy compared with conventional s.c. immunotherapy. In a monocentric open-label trial, 165 patients with grass pollen-induced rhinoconjunctivitis were randomized to receive either 54 s.c. injections with pollen extract over 3 years [cumulative allergen dose 4,031,540 standardized quality units (SQ-U)] or 3 intralymphatic injections over 2 months (cumulative allergen dose 3,000 SQ-U). Patients were evaluated after 4 months, 1 year, and 3 years by nasal provocation, skin prick testing, IgE measurements, and symptom scores. Three low-dose intralymphatic allergen administrations increased tolerance to nasal provocation with pollen already within 4 months (P < 0.001). Tolerance was long lasting and equivalent to that achievable after standard s.c. immunotherapy (P = 0.291 after 3 years). Intralymphatic immunotherapy ameliorated hay fever symptoms (P < 0.001), reduced skin prick test reactivity (P < 0.001), decreased specific serum IgE (P < 0.001), caused fewer adverse events than s.c. immunotherapy (P = 0.001), enhanced compliance (P < 0.001), and was less painful than venous puncture (P = 0.018). In conclusion, intralymphatic allergen administration enhanced safety and efficacy of immunotherapy and reduced treatment time from 3 years to 8 weeks.

The effect of gantry angle on megavoltage photon beam attenuation by a carbon fiber couch insert.

The use of rigid carbon fiber couch inserts in radiotherapy treatment couches is a well-established method of reducing patient set-up errors associated with couch sag. Several published studies have described such inserts as radiotranslucent with negligible attenuation of the radiation field. Most of these studies were conducted with the radiation field normally incident on the couch and there appears to be no evidence in the literature of the effect of the gantry angle on the extent of beam attenuation by the carbon fiber insert alone during external beam radiotherapy. In this study we examined the magnitude of this effect over a range of posterior oblique gantry angles using a cylindrical solid water phantom containing an ionization chamber placed isocentrically. It was found that a 6 MV photon beam, field size 10 x 5 cm, was attenuated significantly as the gantry angle approached the plane of the couch, from 2% at normal incidence and reaching 9% attenuation at angle of incidence 70 degrees. This could have serious implications regarding dose to the treatment volume for treatments requiring posterior oblique angles of incidence with a possible correction factor necessary in monitor unit calculations.

An historical perspective on genomic technologies.

Genomic technologies are best defined as technologies used to manipulate and analyze genomic information. The evolution of this collective power began in earnest with the invention of DNA cloning in the 1970's and most of the technology derives from the last quarter of the 20th century. The historical impact of these technologies is clearly immense. With the genome sequence becoming available for many organisms, including humans, another new view of biology has recently emerged. This review examines the shape and texture of this recent evolution, with a particular emphasis on new technology: DNA cloning, macromolecular structure analysis (X-ray crystallography and NMR), DNA sequencing, DNA synthesis, amplification by the polymerase chain reaction, and transgenic animals (bacteria through mammals).