Challenges in implementing adaptive designs: comments on the viewpoints expressed by regulatory statisticians

This is a discussion of the following three papers appearing in this special issue on adaptive designs: 'FDA's critical path initiative: A perspective on contributions of biostatistics' by Robert T. O'Neill; 'A regulatory view on adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence; and 'Confirmatory clinical trials with an adaptive design' by Armin Koch.     

Adaptive designs from the viewpoint of an academic biostatistician

This is a discussion of the following three papers appearing in this special issue on adaptive designs: 'FDA's critical path initiative: A perspective on contributions of biostatistics' by Robert T. O'Neill, 'A regulatory view on adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence; and 'Confirmatory clinical trials with an adaptive design' by Armin Koch.     

Opening the adaptive toolbox

This is a discussion of the following three papers appearing in this special issue on adaptive designs: 'A regulatory view on adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence; 'Confirmatory clinical trials with an adaptive design' by Armin Koch; and 'FDA's critical path initiative: A perspective on contributions of biostatistics' by Robert T. O'Neill.     

A consultant's perspective on the regulatory hurdles to adaptive trials

This is a discussion of the following two papers appearing in this special issue on adaptive designs: 'A regulatory view on adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence and 'Confirmatory clinical trials with an adaptive design' by Armin Koch.     

Modification of arthropod vector competence via symbiotic bacteria

Some of the world's most devastating diseases are transmitted by arthropod vectors. Attempts to control these arthropods are currently being challenged by the widespread appearance of insecticide resistance. It is therefore desirable to develop alternative strategies to complement existing methods of vector control. In this review, Charles Beard, Scott O'Neill, Robert Tesh, Frank Richards and Serap Aksoy present an approach for introducing foreign genes into insects in order to confer refractoriness to vector populations, ie. the inability to transmit disease-causing agents. This approach aims to express foreign anti-parasitic or anti-viral gene products in symbiotic bacteria harbored by insects. The potential use of naturally occurring symbiont-based mechanisms in the spread of such refractory phenotypes is also discussed.     

Development of 'DFG-out' inhibitors of gatekeeper mutant kinases

HG-7-85-01(22) and HG-7-86-01(26) are thiazolo[5,4-b]pyridine containing type II tyrosine kinase inhibitors with potent cellular activity against both wild-type and 'gatekeeper' mutant T315I- Bcr-Abl. Here we report on the 'hybrid design' concept and subsequent structure activity guided optimization efforts that resulted in the development of these inhibitors.     

Film Review

Book reviewed in this article:
Becoming American . 1982. Produced by Ken Levine and Ivory Waterworth Levine
The Best Place to Live . 1982. Produced and directed by Peter O'Neill and Ralph Rugoff     

Film Reviews

Book reviewed in this article:
The Tree of Iron . 1988. A film by Peter O'Neill, Frank Muhly, Jr ., and Peter Schmidt
The Blooms of Banjeli: Technology and Gender in African Ironmaking . 1986. A film by Carlyn Saltman, Candice Goucher , and Eugenia Herbert     

Eugene O'Neill and Addison's disease

A detailed review of hospital records, physician's notes, diaries, letters, and autopsy reports offers sufficient clinical grounds to establish that Eugene O'Neill developed adrenal insufficiency, secondary to tuberculosis, in later life--a fact hitherto unknown--the condition not becoming manifest until after he had abdominal surgery in 1936.     

Looking Reality in the Eye: Museums and Social Responsibility

Looking Reality in the Eye: Museums and Social Responsibility . Robert P. Janesand Gerald T. Conaty, eds. Calgary: University of Calgary Press, 2005. 196 pp.     

Food-web complexity emerging from ecological dynamics on adaptive networks

Food webs are complex networks describing trophic interactions in ecological communities. Since Robert May's seminal work on random structured food webs, the complexity-stability debate is a central issue in ecology: does network complexity increase or decrease food-web persistence? A multi-species predator-prey model incorporating adaptive predation shows that the action of ecological dynamics on the topology of a food web (whose initial configuration is generated either by the cascade model or by the niche model) render, when a significant fraction of adaptive predators is present, similar hyperbolic complexity-persistence relationships as those observed in empirical food webs. It is also shown that the apparent positive relation between complexity and persistence in food webs generated under the cascade model, which has been pointed out in previous papers, disappears when the final connection is used instead of the initial one to explain species persistence.     

REVIEWS

O n the N orthwest : C ommercial W haling in the P acific N orthwest 1790–1967. Robert Lloyd Webb.
T he S ei W hale : P opulation B iology , E cology and M anagement . Joseph Horwood
W ildlife R adio T agging , E quipment , F ield T echniques and D ata A nalysis . Robert Hayward.
B iology of the G enus C ephalorhynchus . R. L. Brownell, Jr. and G. P. Donovan, eds.
H andbook of M arine M ammals . V olume 4: R iver D olphins and the L arger T oothed W hales . S. H. Ridgway and R. Harrison, eds.
P olar B ears . Ian Stirling.
T he W hales of H awaii . Kenneth C. Balcomb, III.
W hales , D olphins and P orpoises . Richard Harrison and M. M. Bryden, eds.     

Interspecific hybridization induced amplification of Mdm2 on double minutes in a Mus hybrid

We report a case of interspecific hybridization induced amplification of Chromosome 10 on double minutes (dm) in the karyotype of a hybrid Mus embryo. Stable, non-mosaic dm were previously found in tissues of a 16.5-day Mus Musculus x Mus Caroli hybrid (Graves, 1984). Dm in tissues of the hybrid was of interest to us because of previous reports of genomic instability in interspecific hybrids (O'Neill et al., 1998) and thus we decided to characterize the dm in the hybrid karyotypes. Whole chromosome painting of the hybrid cell lines showed amplification of Chromosome 10 sequences. Southern analysis with a probe for the candidate gene Mdm2 showed amplification of the paternal allele of this oncogene. Overexpression of Mdm2 was confirmed by a western analysis that also showed an associated inactivation of the tumor suppressor, Trp53. Evidence indicates that the event leading to the instability observed was an early adaptive response to stress on the genome, i.e. interspecific hybridization.     

Book notices

ENTOMOLOGY IN HUMAN AND ANIMAL HEALTH. 7th edn. By Robert F. Harwood and Maurice T. James
BIOLOGICAL CLOCKS: THEIR FUNCTION IN NATURE. By J. L. Cloudsiey-Thompson
SEXUAL SELECTION AND REPRODUCTIVE COMPETITION IN INSECTS. Edited by Murray S. Blum and Nancy A. Blum
INSECT NEUROPHYSIOLOGICAL TECHNIQUES. By T. A. Miller
INSECT HEMOCYTES. DEVELOPMENT, FORMS, FUNCTIONS AND TECHNIQUES. Edited by A. P. Gupta     

Inhibition of protein crystallization by evolutionary negative design

Why are proteins so hard to crystallize? We propose an 'evolutionary negative design' principle to explain this difficulty. Proteins have evolved to avoid crystallization because crystallization compromises the viability of the cell. Evolutionary negative design is supported by much evidence in the literature, including the effect of mutations on the crystallizability of a protein, the correlations found in the properties of crystal contacts in bioinformatics databases, and the positive use of protein crystallization by bacteria and viruses.     

Audio-Visual Approaches to Science Teaching

From Instinct to Intelligence/How Animals Learn by Gloria Kirshner. Grosset &; Dunlap Publishers, 51 Madison Ave., New York, N.Y. 10010. 1970. 127 pp., $3.95. Reviewed by Robert C. Hayden.

A Pictorial History of Oceanographic Submersibles by James B. Sweeney, Crown Publishers, Inc., 419 Park Ave. South, New York, N.Y. 10016. 1970. 314 pp., Indexed, Bibliography. $9.95. Reviewed by Robert C. Hayden.

Where the Winds Sleep: Man's Future on the Moon—A Projected History by Neil P. Ruzic. Doubleday &; Co., Inc., Garden City, New York, 1970. 236 pp., Indexed. $5.95. Reviewed by Robert C. Hayden.

Hunters and Collectors by George H. T. Kimble. McGraw-Hill Book Co., 330 West 42nd St., New York, N.Y. 10036. 1970. 48 pp., Indexed. $4.95 trade edn., $4.72 lib. edn. Reviewed by Robert C. Hayden.

Life in Ponds by Jean Gorvett. American Heritage Press, New York. 1920. 31 pp. Reviewed by Robert C. Hayden.

Discovering What Goldfish Do by Seymour Simon. McGraw-Hill Book Co., 330 West 42nd St., New York, N.Y. 1970. 47 pp. $3.95 trade edn. $3.83 lib. edn. Reviewed by Robert C. Hayden.

Building and Flying Scale Model Aircraft 3rd Edition by Walter A. Musciano. Herman Publishing Service, Division of Cahners Pub. Co., Inc., 221 Columbus Ave., Boston, Mass. 02116. 1970. 245 pp. Glossary, $7.95. Reviewed by Robert C. Hayden.     

Bat echolocation calls: adaptation and convergent evolution

Bat echolocation calls provide remarkable examples of 'good design' through evolution by natural selection. Theory developed from acoustics and sonar engineering permits a strong predictive basis for understanding echolocation performance. Call features, such as frequency, bandwidth, duration and pulse interval are all related to ecological niche. Recent technological breakthroughs have aided our understanding of adaptive aspects of call design in free-living bats. Stereo videogrammetry, laser scanning of habitat features and acoustic flight path tracking permit reconstruction of the flight paths of echolocating bats relative to obstacles and prey in nature. These methods show that echolocation calls are among the most intense airborne vocalizations produced by animals. Acoustic tracking has clarified how and why bats vary call structure in relation to flight speed. Bats using broadband echolocation calls adjust call design in a range-dependent manner so that nearby obstacles are localized accurately. Recent phylogenetic analyses based on gene sequences show that particular types of echolocation signals have evolved independently in several lineages of bats. Call design is often influenced more by perceptual challenges imposed by the environment than by phylogeny, and provides excellent examples of convergent evolution. Now that whole genome sequences of bats are imminent, understanding the functional genomics of echolocation will become a major challenge.     

BOOK REVIEWS

Fertility and the Family: The Glover Report on Reproductive Technologies to the European Commission
Cross Cultural Perspectives in Medical Ethics: Readings (The Jones and Bartlett Series in Biology) Ed. by Robert M. Veatch
Ending Lives, by Robert Campbell and Diane Collinson
Science and the Unborn: Choosing Human Futures by Clifford Grobstein     

The skull of the rare Malaysian snake Anomochilus leonardi Smith, based on high-resolution X-ray computed tomography

The skull of the rare Malaysian snake Anomochilus leonardi is described in detail on the basis of a high-resolution X-ray computed tomographic scan of a mature specimen. Its skull anatomy is compared with that of Anomochilus weberi , as well as with that of scolecophidians and basal alethinophidians such as Anilius , Cylindrophis , uropeltines and selected Booidea. Anomochilus leonardi is found to be more paedomorphic than Anomochilus weberi . The genus Anomochilus most closely resembles uropeltines in skull anatomy. Both Anomochilus and uropeltines develop a 'central rod design' of skull morphology, which requires the presence of medial frontal pillars, in adaptation to burrowing habits. These pillars are an alethinophidian characteristic, absent in the skull of scolecophidians, which develop an 'outer shell design' in adaptation to burrowing. These results are discussed in the light of the hypothesis that scolecophidians and basal (i.e. non-macrostomatan) alethinophidians are 'regressed macrostomatans'.  © 2007 The Linnean Society of London, Zoological Journal of the Linnean Society , 2007, 149 , 671–685.     

Book Notices

A COLOUR ATLAS OF FRUIT PESTS: THEIR RECOGNITION, BIOLOGY AND CONTROL. By David V. Alford
ECOLOGICAL ENTOMOLOGY. Edited by Carl B. Huffaker and Robert L. Rabb
ECOLOGICAL COMMUNITIES: CONCEPTUAL ISSUES AND THE EVIDENCE. Edited by Donal R. Strong et al.
INSECT CONSERVATION-AN AUSTRALIAN PERSPECTIVE. By T. R. New
APHID ECOLOGY. By A. F. G. Dixon
PEST LEPIDOPTERA OF EUROPE WITH SPECIAL REFERENCE TO THE BRITISH ISLES. By D. J. Carter