The biotechnology innovation machine: a source of intelligent biopharmaceuticals for the pharma industry--mapping biotechnology's success.

The marriage of biotechnology and the pharmaceutical industry (pharma) is predicated on an evolution in technology and product innovation. It has come as a result of advances in both the science and the business practices of the biotechnology sector in the past 30 years. Biotechnology products can be thought of as "intelligent pharmaceuticals," in that they often provide novel mechanisms of action, new approaches to disease control, higher clinical success rates, improved patient care, extended patent protection, and a significant likelihood of reimbursement. Although the first biotechnology product, insulin, was approved just 32 years ago in 1982, today there are more than 200 biotechnology products commercially available. Research has expanded to include more than 900 biotechnology products in clinical trials. Pharma is substantially engaged in both the clinical development of these products and their commercialization.

Waterborne versus dietary zinc accumulation and toxicity in Daphnia magna: a synchrotron radiation based X-ray fluorescence imaging approach.

Recent studies have suggested that exposure of the freshwater invertebrate Daphnia magna to dietary Zn may selectively affect reproduction without an associated increase of whole body bioaccumulation of Zn. The aim of the current research was therefore to investigate the hypothesis that dietary Zn toxicity is the result of selective accumulation in tissues that are directly involved in reproduction. Since under field conditions simultaneous exposure to both waterborne and dietary Zn is likely to occur, it was also tested if accumulation and toxicity under combined waterborne and dietary Zn exposure is the result of interactive effects. To this purpose, D. magna was exposed during a 16-day reproduction assay to Zn following a 5 × 2 factorial design, comprising five waterborne concentrations (12, 65, 137, 207, and 281 µg Zn/L) and two dietary Zn levels (49.6 and 495.9 µg Zn/g dry wt.). Tissue-specific Zn distribution was quantified by synchrotron radiation based confocal X-ray fluorescence (XRF). It was observed that the occurrence of reproductive inhibition due to increasing waterborne Zn exposure (from 65 µg/L to 281 µg/L) was accompanied by a relative increase of the Zn burdens which was similar in all tissues considered (i.e., the carapax, eggs, thoracic appendages with gills and the cluster comprising gut epithelium, storage cells and ovaries). In contrast, the impairment of reproduction during dietary Zn exposure was accompanied by a clearly discernible Zn accumulation in the eggs only (at 65 µg/L of waterborne Zn). During simultaneous exposure, bioaccumulation and toxicity were the result of interaction, which implies that the tissue-specific bioaccumulation and toxicity following dietary Zn exposure are dependent on the Zn concentration in the water. Our findings emphasize that (i) effects of dietary Zn exposure should preferably not be investigated in isolation from waterborne Zn exposure, and that (ii) XRF enabled us to provide possible links between tissue-specific bioaccumulation and reproductive effects of Zn.

Influence of treatment techniques on Cu leaching and different organic fractions in MSWI bottom ash leachate.

The leaching of heavy metals, such as copper, from municipal solid waste incinerator (MSWI) bottom ash is of concern in many countries and may inhibit the beneficial reuse of this secondary material. Previous studies have focused on the role of dissolved organic carbon (DOC) on the leaching of copper. Recently, a study of the Energy Research Centre of The Netherlands (ECN) showed fulvic acid-type components to exist in the MSWI bottom ash leachates and to be likely responsible for the generally observed enhanced copper leaching. These findings were verified for a MSWI bottom ash (slashed circle 0.1-2 mm) fraction from an incinerator in Flanders. The filtered leachates were subjected to the IHSS fractionation procedure to identify and quantify the fractions of humic acid (HA), fulvic acid (FA) and hydrophilic organic carbon (Hi). The possible complexation of fulvic acid with other heavy metals (e.g., lead) was also investigated. The identified role of fulvic acids in the leaching of copper and other heavy metals can be used in the development of techniques to improve the environmental quality of MSWI bottom ash. Thermal treatment and extraction with a 0.2 M ammonium-citrate solution were optimized to reduce the leaching of copper and other heavy metals. The effect of these techniques on the different fractions of organic matter (HA, FA, Hi) was studied. However, due to the obvious drawbacks of the two techniques, research is focused on finding other (new) techniques to treat MSWI bottom ash. In view of this, particle size-based separation was performed to evaluate its effect on heavy metal leaching and on HA, FA and Hi in MSWI bottom ash leachates.

Results of and comments on the 2000 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: The American Association of Academic Chief Residents in Radiology (A3CR2) annually surveys radiology residency programs on issues related to training. The objective is to highlight national similarities, differences, and trends to help programs establish standards and improve residency training. MATERIALS AND METHODS: Questionnaires were mailed to 180 accredited diagnostic radiology residency training programs in the United States. The survey covered the usual general topics and more specific topics considered every 4 years; for 2000 the latter were on-call issues and the chief residency year. RESULTS: Completed surveys were returned from 63 programs (35%). Important findings included increased caseload and call commitments, especially for smaller programs. Resident salaries appear to have increased more than the consumer price index. Nonemergent after-hour coverage and teleradiology are now a large part of the resident work practice. Women continue to be underrepresented, with a trend downward. Chief residents are more involved in organizing preparation for board examinations and have greater office facilities and more administrative duties. CONCLUSION: This survey provided useful insights. All levels of residency face increased workloads. On-call hours have not changed, but the work has intensified and the use of teleradiology has increased. Many programs have adopted a "night-float" system, and nonemergent after-hours coverage should be considered in any program evaluation. Continued vigilance and sustained efforts are required to ensure that radiology is considered as a specialty by both men and women. With increased demands on attending physicians' time, chief residents may need to take on more administrative responsibilities.

Results of and comments on the 1998 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: The American Association of Academic Chief Residents in Radiology annually surveys residency programs on a variety of issues related to residency training. The survey allows for comparison between programs regarding training and follows trends on current issues. MATERIALS AND METHODS: Questionnaires were mailed to all accredited programs in the United States (188 programs). The questionnaire consisted of questions regarding general demographic information and specific topics regarding residency training. The 1998 survey focused on turf issues, teleradiology use, residency selection, and prior training. RESULTS: Completed surveys from 61 programs (32.4%) were returned. Important findings included (a) the ongoing turf battles regarding vascular and obstetric-gynecologic ultrasound, both in general hospital and emergency department patients, (b) the use of teleradiology by most residents, and (c) the low percentage of women in radiology residency programs. CONCLUSION: The information obtained during yearly surveys is useful for program evaluation and future planning. Current survey results indicate an increasing use of teleradiology in residency over the past 4 years. The turf battles in ultrasonography (both vascular and obstetric) have remained unchanged over the same time frame.

Results of the 1997 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: The American Association of Academic Chief Residents in Radiology annually surveys residency programs on a variety of issues related to residency training. The survey results allow individual programs to compare features of their programs with national averages and to gauge trends in radiology residency training. MATERIALS AND METHODS: Questionnaires were mailed to the chief residents in 180 accredited radiology residency programs in the United States. A variety of demographic and common-interest questions were asked. The 1997 survey focused on American Board of Radiology (ABR) examination preparation, residency curriculum, and socioeconomic issues relevant to graduating radiology residents. RESULTS: Completed surveys from 73 programs (41%) were returned. Areas of curriculum concern among chief residents reflected primarily current turf issues. A higher than expected percentage of residents considered their training to be inadequate in nonneurologic magnetic resonance imaging and chest, musculoskeletal, and genitourinary radiology. Job security is a major emerging concern for radiology residents who are considering careers in private practice. The practice of remembering and transcribing questions from the ABR written examination is common, and these questions are a valued resource in preparing for the diagnostic section of the written examination. Most residents attend a commercial review course before the oral examination, and the majority of programs also provide internal review courses. CONCLUSION: A higher than expected percentage of chief residents expressed concern regarding training in subspecialties of radiology that are neither areas of turf dispute nor areas where certificate of additional qualification examinations are offered. Radiology programs and residents expend substantial resources on preparation for the ABR examinations in addition to the usual 4-year curriculum. The most valued resource for the diagnostic section of the examination is almost certainly not equally available. Radiology residents are increasingly concerned about future job security.

Results of the 1996 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: Diagnostic radiology chief residents were surveyed on issues related to residency training to compare features and gauge trends in training. METHODS: Questionnaires were mailed to accredited programs in the United States. A variety of demographic and common-interest questions were asked. RESULTS: Forty-three percent of surveys were returned. The percentage of female residents was similar to that reported in other recent surveys; however, the percentage of women among 1st-year residents had decreased. Resident salaries had increased, although the average salary for a 4th-year resident had decreased when adjusted for inflation. Most 1st-year residents started participating in overnight hospital coverage by their 12th month of residency, and the total number of call days during residency correlated inversely with the size of the residency program. Almost half of residency programs used a night-float resident to provide after-hours coverage. CONCLUSION: The information derived from the survey should be useful for program evaluation and future planning.

Evaluation of biotechnology products.

Biotechnology products have had a substantial impact on the health care system, including cost and patient care. In some hospitals, agents produced by biotechnology account for 10% or more of the pharmacy budget. As of May 1996, 29 biological products had been approved for use in the United States, including, in many instances, agents for diseases or conditions for which no drugs were previously available. These compounds are different molecules, often with very different types of properties from synthetic chemicals. They are relatively expensive compared with traditionally manufactured synthetic drugs. The increasing availability, individual characteristics, and relative expense of these products mandate a systematic method of evaluating them for use in various health care systems. Thirteen essential points must be considered when evaluating them for clinical use: availability of alternative agents; indications (both labeled and unlabeled); glycosylation; adverse events; administration and pharmacokinetics; monitoring needs; shipping, handling, and storage; stability; pharmaco-economic studies; concomitant drug costs; special pharmacy procedures; reimbursement; and manufacturer's support.

Results of the 1994 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: Radiology chief residents are surveyed annually and the data are used to improve the training of diagnostic radiology residents. METHODS: Questionnaires were mailed to accredited programs in the United States and Canada. A variety of demographic and common-interest questions were asked. For the first time, an individual resident questionnaire also was included. RESULTS: Completed surveys from 53 programs (42%) were returned. The percentage of female residents was similar to that reported in other recent surveys. Resident salaries continued to increase. Residency selection remained highly competitive. Residents indicated that the utility of a fellowship in radiology exceeded the utility of clinical training in other fields prior to the radiology residency. Residents agreed with recommendations by the American Association of Academic Chief Residents in Radiology concerning proposed changes in the American Board of Radiology (ABR) examinations. CONCLUSION: The information derived from the surveys on resident selection, the utility of preradiology clinical training, and the ABR examination may be useful for residents, program directors, and departmental chairs.