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Pay for performance (P4P) is increasingly being used to stimulate healthcare providers to improve their performance. However, evidence on P4P effectiveness remains inconclusive. Flaws in program design may have contributed to this limited success. Based on a synthesis of relevant theoretical and empirical literature, this paper discusses key issues in P4P-program design. The analysis reveals that designing a fair and effective program is a complex undertaking. The following tentative conclusions are made: (1) performance is ideally defined broadly, provided that the set of measures remains comprehensible, (2) concerns that P4P encourages "selection" and "teaching to the test" should not be dismissed, (3) sophisticated risk adjustment is important, especially in outcome and resource use measures, (4) involving providers in program design is vital, (5) on balance, group incentives are preferred over individual incentives, (6) whether to use rewards or penalties is context-dependent, (7) payouts should be frequent and low-powered, (8) absolute targets are generally preferred over relative targets, (9) multiple targets are preferred over single targets, and (10) P4P should be a permanent component of provider compensation and is ideally "decoupled" form base payments. However, the design of P4P programs should be tailored to the specific setting of implementation, and empirical research is needed to confirm the conclusions.

Recently, the state of California enacted a law requiring radiologists to record the radiation dose that each patient receives for a CT scan. Failure to do so is penalized by law. This law becomes effective in July 2012. By July 2013, every facility that performs CT scans must become accredited by one of three professional groups. This report discusses the role that legislation is playing in the practice of medicine in regard to CT practice. Inherent in this discussion is the assumption that pediatric radiologists know the right dose that a child should receive for a specific clinical indication. But do we really know the answer to this? Compared to the European radiology community, the United States radiology community lags in this regard. This paper defines diagnostic reference levels (DRL) and reviews the history of DRL in the United States compared to that in the European community and the progress by the American College of Radiology's National Radiology Data Registry (NRDR) to establish national registries. The establishment of the first pediatric Quality Improvement Registry in CT Scans in Children (QuIRCC) and its progress to date will be discussed.

Interventional radiology techniques to treat oncological disease have already shown value in adults. The adoption and development of interventional oncology (IO) in children have been more limited and challenging. This relates to the approval process for new devices and agents, oncology group protocol limitations and the inherent hesitation of trying new treatments in children. This paper will discuss how new procedures are developed and approved, and the new therapies that will become available to better treat pediatric malignancies. Bringing the benefits of IO to children will require initiative on the part of pediatric diagnostic and interventional radiologists as well as the cooperation of our clinical colleagues.

Pediatric radiologists who practice prenatal imaging are often at the front lines of communication with pregnant patients and their partners. The communication process is particularly complex when a fetal abnormality is diagnosed. Regardless of whether the information is completely new and unexpected, or the patient is referred for tertiary imaging and counseling, few pediatric radiologists are trained specifically in the communication skills necessary to provide optimal care to the prospective parents. This paper reviews current literature regarding communication with patients about unexpected or difficult information, and illustrates key clinical and ethical features that make conversations with pregnant patients particularly challenging in the setting of fetal abnormalities.

The following paper presents the methodology and results of a costing exercise of maternal health services in Tanzania. The main objective of this study was to determine the actual costs of antenatal and obstetric care in different health institutions in a district in Tanzania as a basis of more efficient resource allocation. A costing tool was developed that allows the calculation of costs of service units, such as deliveries and antenatal care, and separates these costs from the costs of other services. Time consumed by each activity was used as an allocation key. For that purpose, we recorded the personnel consumption with different time-study methodologies. This approach was tested and implemented in Mtwara Urban District, South Tanzania. The results were analyzed by a spreadsheet program. The paper presents average costs for different costing units of maternal care. Among other findings, we found that the cost of a normal vaginal delivery is US $12.30 in a dispensary and US $6.30 in the hospital--a result that needs explanation, as usually one would expect that hospitals are more cost-intensive than first-line facilities. However, dispensaries are grossly underutilized so that the costs per service unit are rather high. The cost for surgical delivery (only in hospitals) was found to be US $69.26 and the average cost per antenatal care consultation (only at dispensaries) was US $2.50. We conclude that improved planning of elective services is a prerequisite for more effective and efficient use of personnel resources. In addition, the definition of medically and economically sound standards, in particular staffing standards, is critical to make cost analysis an effective management tool to guide rational resource allocation.

Eight different analytical extraction procedures commonly used to extract mercury species from biological samples were evaluated by analyzing Tuna Fish Tissue Certified Reference Material (ERM-CE464) certified for the content of total mercury and methylmercury. Speciated isotope dilution mass spectrometry (SIDMS; US Environmental Protection Agency's method 6800) was utilized to evaluate and effectively compensate for potential errors during measurement and accurately quantify mercury species using all the extraction methods. SIDMS was used to accurately evaluate species transformations during sample pretreatment, preparation and analysis protocols. The extraction methods tested in this paper were based on alkaline extraction with KOH or tetramethylammonium hydroxide; acid leaching with HCl, HNO(3) or CH(3)COOH; extraction with L: -cysteine hydrochloride; and enzymatic digestion with protease XIV. Detection of total mercury and mercury species from all extraction methods was carried out by inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography-ICP-MS, respectively. Microwave-assisted extraction and ultrasound-assisted extraction were found to be the most efficient alkaline digestion protocols that caused the lowest levels of transformation of mercury species (6% or less). Extraction with 5 M HCl or enzymatic digestion with protease resulted in the second-highest extraction efficiency, with relatively lower transformation of methylmercury to inorganic mercury (3 and 1.4%, respectively). Despite frequent use of acid leaching for the extraction of mercury species from tuna fish samples, the lowest extraction efficiencies and the highest mercury species transformation were obtained when microwave-assisted extraction with 4 M HNO(3) or CH(3)COOH was used. Transformations as high as 30% were found using some literature protocols; however, all the extractions tested produced accurate quantitation when corrected in accordance with the SIDMS method standardized in the US Environmental Protection Agency's method 6800. [figure: see text]

Nitric oxide (NO), also known as endothelium-derived relaxing factor, is produced by endothelial nitric oxide synthase (eNOS) in the intima and by neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels. It dilates the arteries in response to shear stress, metabolic demands, pterygopalatine ganglion stimulation, and chemoregulation. Subarachnoid haemorrhage (SAH) interrupts this regulation of cerebral blood flow. Hemoglobin, gradually released from erythrocytes in the subarachnoid space destroys nNOS-containing neurons in the conductive arteries. This deprives the arteries of NO, leading to the initiation of delayed vasospasm. But such vessel narrowing increases shear stress, which stimulates eNOS. This mechanism normally would lead to increased production of NO and dilation of arteries. However, a transient eNOS dysfunction evoked by an increase of the endogenous competitive nitric oxide synthase (NOS) inhibitor, asymmetric dimethyl-arginine (ADMA), prevents this vasodilation. eNOS dysfunction has been recently shown to be evoked by increased levels of ADMA in CSF in response to the presence of bilirubin-oxidized fragments (BOXes). A direct cause of the increased ADMA CSF level is most likely decreased ADMA elimination due to the disappearance of ADMA-hydrolyzing enzyme (DDAH II) immunoreactivity in the arteries in spasm. This eNOS dysfunction sustains vasospasm. CSF ADMA levels are closely associated with the degree and time-course of vasospasm; when CSF ADMA levels decrease, vasospasm resolves. Thus, the exogenous delivery of NO, inhibiting the L-arginine-methylating enzyme (IPRMT3) or stimulating DDAH II, may provide new therapeutic modalities to prevent and treat vasospasm. This paper will present results of preclinical studies supporting the NO-based hypothesis of delayed cerebral vasospasm development and its prevention by increased NO availability.

This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST.

Rationale: Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures. Designing studies that consider the consumer's perspective will help to forge a better alliance between participants and researchers., Objective: Participant satisfaction is seldom assessed in pharmacological research. In this paper, we report on parent satisfaction in a randomized clinical trial in children with autistic disorder and severely disruptive behavior., Method: Parents of 101 children with autism who had participated in a multi-site 8-week double-blind clinical trial of risperidone were given a questionnaire at the end to elicit their perceptions of the appropriateness and acceptability of clinical trial procedures., Results: Ninety-six (95.0%) parents returned the questionnaire. Of these, 80.0 to 96.8%, depending on the question, expressed satisfaction with their child's research participation regardless of treatment outcome or assignment to active drug or placebo. In all, 90.5% of parents indicated that they would "definitely" recommend the clinical trial to other families with similar children. A total of 92.7% indicated that they would rejoin the clinical trial if they had to do it all over again. Ethnic minority subjects were more satisfied than white participants with the use of "learning tests"., Conclusions: Parents of children participating in this trial were highly satisfied and supportive of the clinical trial procedures. Random assignment to drug or placebo and the clinical response of their children did not appear to influence their views. Further satisfaction studies of this sort are encouraged.

Modern sanitary practices result in large volumes of human waste, as well as domestic and industrial sewage, being collected and treated at common collection points, wastewater treatment plants (WWTPs). In recognition of the growing use of sewage sludge as fertilizers and soil amendments, and the scarcity of current data regarding the chemical constituents in sewage sludge, the US National Research Council (NRC) in 2002 produced a report on sewage sludge. Among the NRC's recommendations was the need for investigating the occurrence of pharmaceuticals and personal care products (PPCPs) in sewage sludge. PPCPs are a diverse array of non-regulated contaminants that had not been studied in previous sewage sludge surveys but which are likely to be present. The focus of this paper will be to review the current analytical methodologies available for investigating whether pharmaceuticals are present in WWTP-produced sewage sludge, to summarize current regulatory practices regarding sewage sludge, and to report on the presence of pharmaceuticals in sewage sludge.

The nature of intracellular communication and integration in the central nervous system remained a source of controversy long after it had been accepted that the brain is intrinsically involved in the reception of external and internal sensory impressions, in the control of both voluntary and involuntary physiological functions, and in the processes associated with consciousness and psychic function in humans. The role of the specific chemistry of the brain in these functions was specifically addressed only in the 20th century, although chemical examination of brain tissue can be traced at least as far back as 1719 to Hensing's Cerebri examen chemicum. Throughout the 1940s and 1950s evidence accumulated from a variety of laboratories that certain chemical substances, such as acetylcholine, noradrenaline and histamine, might be involved in central nervous system neurotransmission, but conclusive evidence for such communication was difficult to obtain. Commencing with Carlsson's 1957 paper on the anti-reserpine effects of DOPA and culminating in the successful amelioration of parkinsonian akinesia by Birkmayer and Hornykiewicz via administration of L-DOPA in 1961, followed by the identification of specific nervous tracts which utilized dopamine as a transmitter, chemical neurotransmission in the brain was ultimately demonstrated through a combination of pharmacological, physiological and clinical research. Neurochemistry had thereby graduated from a branch of general physiology to being centrally involved in models of central nervous system function.

Recent market withdrawals of prescription drug products have brought attention to premarketing safety research. Less known but related to some drug withdrawals are postmarketing dosage changes of newly marketed drugs, including both dosage reductions and increases. These events have serious effects on patients, manufacturers, and regulatory authorities. Most of these harmful events could be avoided by intensive employment of targeted clinical pharmacology investigations to optimize dosage prior to phase III testing and regulatory approval. In this paper, the frequency and implications of postmarketing dosing changes and market withdrawals are considered in light of approaches to preventing them.

As interventional procedures have become progressively more sophisticated and lengthy, the potential for high patient radiation dose has increased. Staff exposure arises from patient scatter, so steps to minimize patient dose will in turn reduce operator and staff dose. The practice of ALARA in an interventional radiology (IR) suite, therefore, requires careful attention to technical detail in order to reduce patient dose. The choice of imaging modality should minimize radiation when and where possible. In this paper practical steps are outlined to reduce patient dose. Further details are included that specifically reduce operator exposure. Challenges unique to pediatric intervention are reviewed. Reference is made to experience from modern pediatric interventional suites. Given the potential for high exposures, the practice of ALARA is a team responsibility. Various measures are outlined for consideration when implementing a quality assurance (QA) program for an IR service.

This paper discusses pediatric image quality and radiation dose considerations in state-of-the-art fluoroscopic imaging equipment. Although most fluoroscopes are capable of automatically providing good image quality on infants, toddlers, and small children, excessive radiation dose levels can result from design deficiencies of the imaging device or inappropriate configuration of the equipment's capabilities when imaging small body parts. Important design features and setup choices at installation and during the clinical use of the imaging device can improve image quality and reduce radiation exposure levels in pediatric patients. Pediatric radiologists and cardiologists, with the help of medical physicists, need to understand the issues involved in creating good image quality at reasonable pediatric patient doses. The control of radiographic technique factors by the generator of the imaging device must provide a large dynamic range of mAs values per exposure pulse during both fluoroscopy and image recording as a function of patient girth, which is the thickness of the patient in the posterior-anterior projection at the umbilicus (less than 10 cm to greater than 30 cm). The range of pulse widths must be limited to less than 10 ms in children to properly freeze patient motion. Variable rate pulsed fluoroscopy can be leveraged to reduce radiation dose to the patient and improve image quality. Three focal spots with nominal sizes of 0.3 mm to 1 mm are necessary on the pediatric unit. A second, lateral imaging plane might be necessary because of the child's limited tolerance of contrast medium. Spectral and spatial beam shaping can improve image quality while reducing the radiation dose. Finally, the level of entrance exposure to the image receptor of the fluoroscope as a function of operator choices, of added filter thickness, of selected pulse rate, of the selected field-of-view and of the patient girth all must be addressed at installation.

Objective: Occupational noise exposure and noise-induced hearing loss (NIHL) among construction workers has long been recognized as a problem in the United States, yet little is known about the prevalence of NIHL among American construction workers. The purpose of this study was to determine the prevalence and characteristics of hearing loss among operating engineers (OEs) who operate heavy construction machinery., Method: As a part of hearing protection intervention, an audiometric test was conducted for both ears at frequencies 0.5 through 8 kHz in the soundproof booth. Prior to the audiometric test, a paper-pencil pre-hearing test questionnaire was administered and an otoscopic examination was completed. Prevalence of hearing loss was determined based on hearing threshold levels (HTLs) in the worst ear with a low fence of 25 dB., Result: A total of 623 workers were included in the analysis and they were predominantly middle-aged Caucasian males (mean age = 43 years, Caucasian = 90%, male = 92%). Over 60% of OEs showed hearing loss in the noise-sensitive higher frequencies of 4 and 6 kHz. The rate of hearing loss was particularly higher among workers who reported longer years of working in the construction industry. Workers showed significantly poorer hearing in the left ear, and a typical characteristic of NIHL, a V-notch at 4 or 6 kHz, was not shown in this population. Thirty-eight percent reported ringing/buzzing in the ear and 62% indicated having problems in understanding what people say in loud noise. Average reported use of hearing protection devices (HPDs) was 48% of the time they were required to be used. Significant inverse relationship was found between higher frequency (4-6 kHz) hearing loss and use of HPDs (r =-0.134, p < 0.001). Workers using HPDs more had significantly better hearing than those who did not., Conclusion: The study demonstrated a significant NIHL problem and low use of HPDs in OEs. An effective hearing conservation program, including a periodic audiometric testing and hearing protection intervention, for this study population should be in place.

Despite the widespread use of the USEPA method (U.S. Environmental Protection Agency, 40 CFR 136 Appendix B) for the determination of method detection limit (MDL), criticisms have been raised that the method does not account for measurement bias and outliers that subsequently lead to a common misunderstanding of the requirement for the determination of MDL. This paper demonstrates that it is difficult to follow the USEPA method for verifying the MDL for analysis involving multiple metals and proposes a precision and bias criterion for determining the MDL. A multiple-point fitted profile, based on the correlation between relative standard deviation (RSD) and concentration, is used to derive a robust MDL value. Representative examples of As, Ca, Cr, and Cu are used to illustrate this procedure. A procedure for identifying outliers is also discussed.

Urine samples collected in 1999 and 2000 as part of the National Health and Nutrition Examination Survey (NHANES) were analyzed for 14 monohydroxy polycyclic aromatic hydrocarbons (PAHs), and, for the first time, reference range values were calculated for these metabolites in the US population. Pyrene is a major component of most PAH mixtures and often is used as a surrogate for total PAH exposure. We detected 1-hydroxypyrene (1-OHpyrene), a metabolite of pyrene, in more than 99% of the samples. The overall geometric mean concentration for 1-OHpyrene in the USA was 79.8 ng/l, with a 95% confidence interval (CI) of 69.0-92.2 ng/l. The overall geometric mean creatinine-adjusted urinary 1-OHpyrene levels in the USA was 74.2 ng/g creatinine (0.039 micromol/mol), with a 95% CI of 64.1-85.9 ng/g creatinine (0.034-0.046 micromol/mol). There were no statistically significant differences among age, gender, or race/ethnicity groups. Adult smokers in the USA have urinary 1-OHpyrene levels three times higher than those of non-smokers. This difference was statistically significant. In this paper, we compare the reference range of urinary 1-OHpyrene levels with levels reported from various occupations by other researchers.

NIST maintains a portfolio of more than 1300 standard reference materials (SRM), more than a third of these relating to measurements in the biological and environmental fields. As part of the continuous renewal and replacement efforts, a set of new marine sediments has been recently developed covering organic and inorganic determinations. This paper describes the steps taken in sample preparation, homogeneity assay, and analytical characterization and certification with specific emphasis on SRM 2702 inorganics in marine sediment. Neutron activation analysis showed the SRM to be highly homogeneous, opening the possibility for use with solid sampling techniques. The certificate provides certified mass fraction values for 25 elements, reference values for eight elements, and information values for 11 elements, covering most of the priority pollutants with small uncertainties of only several percent relative. The values were obtained by combining results from different laboratories and techniques using a Bayesian statistical model. An intercomparison carried out in field laboratories with the material before certification illustrates a high commutability of this SRM.

Rationale: This article is intended to explore how minority status and cultural factors affect the participation of subjects in clinical psychopharmacology research., Objectives and Methods: A literature review was performed using key words "clinical psychopharmacology trials", "psychiatric ethics" and "minority groups". Major goals of this review were to examine current knowledge base and identify existing gaps in this fairly new area of psychiatric research., Results: We found extremely few papers addressing the issue directly. Most references to minority groups were made peripherally, and many of these were extrapolated to psychiatric patients from work done on medical populations. We found no empirical studies done in psychiatric populations., Conclusions: Systematic, well-designed research studies are needed to elucidate how culture, race and ethnicity impact on such issues as accrual, retention, informed consent and safeguards against the potential exploitation of minority research subjects. On the basis of the literature review and our personal experience doing clinical research with minority patients, we provide several recommendations and specific suggestions to clinical researchers who include minority patients in their clinical trials.

Rationale: There is a broad range of complex ethical issues in the conduct of psychopharmacological drug studies that go beyond the question of the ethics of placebo controls. However, our empirical knowledge with respect to these issues is very limited. This review, although not exhaustive, highlights an array of ethical issues that arose from discussions within the NIMH Human Subjects Research Council Workgroup., Objectives: To delineate issues in psychopharmacological drug studies that require debate and would benefit from research leading to the development of empirically-supported guidelines., Methods: Information included in this report was drawn from the first author's participation as chair of the NIMH Human Subjects Research Council Workgroup, guidelines for the ethical conduct of research proposed by professional organizations to which the first and third author belong, and relevant research literature., Results: We have focused on general issues relating to informed consent, research with special populations, and long-term treatment studies. Additionally, we raise issues relevant to large research-oriented institutions., Conclusions: The essential ethical challenge in psychopharmacological trials is to balance risks and benefits in the context of the needs and capacities of individual research subjects. The IRB system must become evidence-based and not rely on unproven assumptions. Specific research studies should be undertaken to address many of the issues of informed consent and research ethics postulated in this paper.

Unlabelled: This paper discusses the arguments for and against radical tumor resection as a strategy for treatment of cerebral gliomas., Method: Data from the Glioma Outcome Project were analyzed to determine whether survival could be related to extent of resection in 666 patients treated by biopsy or resection for malignant cerebral gliomas., Findings: Consistent survival advantages were noted for those patients treated with resection., Interpretation: This observational study, although undoubtedly reflecting selection bias, provides data that support resection as a major factor in survival after surgery for malignant gliomas.

Chronic myeloid leukemia (CML) invites biologically based radiation risk modeling because CML is simultaneously well-understood, homogeneous and prevalent. CML is known to be caused by a translocation involving the ABL and BCR genes, almost all CML patients have the BCR-ABL translocation, and CML is prevalent enough that its induction is unequivocally detected among Hiroshima A-bomb survivors. In a previous paper, a linear-quadratic-exponential (LQE) dose-response model was used to estimate the lifetime excess risk of CML in the limit of low doses of gamma-rays, R gamma. This estimate assumed that BCR-ABL translocation dose-response curves in stem cells for both neutrons and gamma-rays, differ only by a common proportionality constant from dicentric aberration dose-response curves in lymphocytes. In the present paper we challenge this assumption by predicting the BCR-ABL dose response. The predictions are based on the biophysical theory of dual radiation action (TDRA) as it applies to recent BCR-to-ABL distance data in G0 human lymphocytes; this data shows BCR and ABL geometric distributions that are not uniform and not independent, with close association of the two genes in some cells. The analysis speaks against the previous proportionality assumption. We compute 11 plausible LQE estimates of R gamma, 2 based on the proportionality assumption and 9 based on TDRA predictions. For each estimate of R gamma we also compute an associated estimate of the number of CML target cells, N; the biological basis of the LQE model allows us to form such estimates. Consistency between N and hematological considerations provides a plausibility check of the risk estimates. Within the group of estimates investigated, the most plausible lifetime excess risk estimates tend to lie near R gamma = 0.01 Gy-1, substantially higher than risk estimates based on the proportionality assumption.

Studies of error and adverse events in medicine have brought a growing awareness of the extent of harm to patients. The psychology of human error strongly suggests that individual liability to error is strongly influenced by the conditions and organisation of the working environment and the nature of the task, in particular the complex and inherently uncertain judgements frequently made in medicine. Research into accidents in medicine and other high risk areas has lead to a much broader concept of causation, with less focus on individuals and more on pre-existing organisational factors. These ideas have been adapted to practical use in healthcare in the analysis of adverse events and in working towards developing safer systems of care. The final section of the paper summarises the implications of this approach for healthcare in terms of an overall systems approach, the need for basic information about clinical incidents, the benefits of systematic investigation and analysis, the nature of safety interventions, the need to study success as well as failure and the need to develop an open, safety aware culture in healthcare.

Background: Trauma remains a major problem throughout the world. The prognosis of severe eye injuries is commonly bleak. This paper focuses on the epidemiology of eye trauma, the role of ocular epidemiology, and identification and reduction of risk factors., Methods: An analysis of the first 8,952 patients reported with severe eye injuries, defined as those eye injuries resulting in permanent and significant (measurable and observable on routine eye examination) structural and/or functional changes to the eye, from the United States Eye Injury Registry as of 31 July 1998., Results: The age of patients entered was from the 1st year of life to 103 years. Fifty-eight percent of those injured were less than 30 years of age. The male to female ratio was 4.6:1, reaching 7.4:1 in the fourth decade of life. Almost half of the injuries involved the retina, and 77% of the injured eyes required one or more surgical procedures, including a large proportion which have undergone vitreoretinal surgical procedures., Conclusion: Injuries remain the most serious public health problem facing developed nations. Yet, a persistent inadequacy exists both in the standardized documentation of eye injuries and in their treatment. With appropriate surgical and medical intervention, a majority of the reported injured eyes recovered functional levels of visual acuity. It appears that glasses, including prescription glasses and even non-prescription sunglasses, can offer measurable protection which results in a lower incidence of severe eye injuries to those wearing glasses.

Besides personal experience as a former research fellow, the prerequisites for a successful research fellowship in the USA were analysed. Individual initiatives without any infrastructure for successful reintegration at home will fail. Isolated publications will carry the insignia of the guest university without providing benefit for the home institution at a later stage. The ideal constellation is the continuity of international cooperation in combination with an active research group at home. In addition to the respective publications, the following achievements of a research period in the USA can be attained: Establishing ongoing contacts to an international research group in the own field of interest; training in "how to write a scientific paper"; introduction to the "international scientific community". The potential contact to other groups cannot be planned, but represents an important aspect of a research period. To learn to appreciate other peoples' way of living adds to the personality of every scientist.

The present study analyses a selection of German and American surgical and cancer research journals from the years 1984 and 1994. The aim of the study was to evaluate the amount of publications by German surgeons in these journals. Furthermore, any influence of the impact factor on the publication criteria was analyzed. German surgical journals showed a high percentage increase in the impact factor but are, in absolute numbers, still significantly behind the American journals. In parallel, German surgeons are still the major contributors to German language journals, but increasingly publish in the American ones as well. The impact factor is one of the major selection criteria on to which journal a paper shall be submitted.

This paper summarizes the worldwide cumulative experience with copolymer 1 (Copaxone) in 857 patients who were enrolled in open-label (n = 586), double-blind (n = 201), and compassioniate-use studies (n = 70). The results of a phase III study, including previously unpublished information, are employed to delineate adverse events that occur more frequently among patients treated with copolymer 1 than in placebo-treated controls, and to provide qualitative information. In the cumulative database, patients usually had relapsing-remitting multiple sclerosis and typically received a dose of 20 mg by daily subcutaneous injection for at least 1 year, and occasionally for more than 10 years. Withdrawal rates were 8% for copolymer 1 and 2% for placebo. The most common adverse event was mild injection-site reaction, manifested by erythema, inflammation, and induration. The most remarkable adverse event was a systemic post-injection reaction that occurred in 10% of patients. It was manifested by flushing, chest tightness, palpitations, dyspnea, and anxiety, and was acute and transient. The incidence of adverse events associated with interferon beta, such as flu-like syndrome, depression, hematologic abnormalities, cardiotoxicity, and elevated hepatic enzymes, was not increased among patients treated with copolymer 1. Evaluation of the extensive experience with copolymer 1 confirms that it is well tolerated and suitable for self-administration by patients with multiple sclerosis.

This paper is a "historical account" of the entire process leading to the final implementation of a toxicology research program on the health-effect studies of pesticide and fertilizer contaminants in groundwater conducted at the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP). Starting with the perception of a potential problem area, the program evolved through several stages, including planning and information-gathering, deliberation on experimental designs, formulation of a draft protocol, peer-review and public comments on the protocol, finalization of the protocol, announcement of open bidding to the NTP master agreement laboratories (i.e., a group of laboratories that has been previously evaluated and approved to conduct NTP toxicology contract work), implementation of chemistry developmental work, selection of toxicology laboratories and awarding of contracts, final implementation of toxicology studies, and cultivation of special collaborative efforts among NIEHS in-house scientists as well as colleagues at the neighbouring laboratories in Research Triangle Park. To put things in perspective, the author's present approach, a coupling of physiologically based pharmacokinetics/pharmacodynamics and computer modeling with the toxicology of chemical mixtures at Colorado State University, is used to address the issues of toxicology and risk assessment of chemical mixtures with respect to rationale and reality.

"This paper takes several surveys of the literature concerning migration research as its starting point and directs the reader toward a number of potentially fruitful lines for future research. Major sections include one on modeling migrant choice in which the pros and cons of using gross versus net migration measures are discussed. A second introduces and discusses the concept of a 'spatial' choice set, which has the potential to be implemented with laboratory experimental techniques. The third involves a wide-ranging discussion of new directions in modeling the interrelationships between employment and migration." The primary geographical focus is on the United States., (excerpt)

"In determining metropolitan population size and changes therein, urban theorists traditionally have focused on the number of occupied dwelling units or households and have assumed that these households are equal in size. This paper argues that average household size is an indicator of how intensively the housing stock is utilized and that there is substantial variation in household size across SMSAs in the U.S. The experience of 150 SMSAs is examined for the time period 1960 to 1970. The study model attributes varying household size to differentials in birth and divorce rates, racial composition and age of housing. Ramifications of recent household size declines involve the internal spatial organization of metropolitan areas and the Census controversy with cities over alleged undercounts of urban populations.", (excerpt)

"This paper is a comparison of two contrasting methods for projecting population at the regional and state levels. A projection of the U.S. Bureau of the Census employs standard demographic methods, while the population projection by Data Resources, Inc., is based on economic opportunity. The methodological differences between these two projections are discussed, and the projections for the year 2000 are compared....The U.S. Bureau of the Census projects population decline in the Northeast and rapid growth in the West while Data Resources, Inc., projects some population growth in the Northeast and less rapid growth in the West.", (excerpt)

This paper is a survey of the literature in an attempt to provide the basis for our current understanding of the disciform process. Particular emphasis is placed on its pathogenesis and the role of subretinal neovascularization. No two lesions appear exactly alike because of the many stages and combinations possible. Gass (1967) has delineated the broad spectrum with the many different clinical manifestations of this disease process. Verhoeff and Grossman (1937) provided the histopathologic basis for our understanding of the disciform process. The histologic correlation of the clinical "predisciform" state would seem to offer the most promising information for understanding the pathogenesis of the disciform process (Frank et al. 1973; Green and Key 1977; Kornweig 1967; Sarks 1973 and 1976; Small et al. 1976; Zauberman 1970). It is hoped that this literature review has sufficiently emphasized the inherent deficiencies of strictly clinical studies and the need for an appropriate experimental animal model (Ryan 1979).

"This paper has examined the impact of climate on migration. It has compared the results that are obtained when various indicators of climatic conditions, both those which have been used in the literature and those which have not, are included in a regression used to explain migration behavior. The results suggest that individuals do indeed consider climatic conditions in different areas when deciding where to live; people generally prefer areas which have moderate climates to areas which have either extremely hot or extremely cold climates. The results also indicate that the climate variables which yield the best results are generally those which have not been used in the literature." The study is based on U.S. data concerning in-migration to 36 SMSAs between 1960 and 1970., (excerpt)

Max Wertheimer, the chief founder of an experimentally based Gestalt psychology, conducted his pioneering studies in motion perception on new theoretical grounds. Since the influence of this approach may be greater in today's cognitive psychology than it has ever been during the half-century of introspectionism and radical behaviorism, it is appropriate to review the actual roots of Wertheimer's (1912) seminal publication and his continuing research on apparent and real motion perception in the light of past and recent work. Illustrative examples, especially of Wertheimer's early research, are provided in this paper. The implications of his experimentation and biopsychological theorizing are still of major interest for present psychological inquiry. Nevertheless, the need for more future systematic comparative research on motion perception must be emphasized. The Epilogue of this paper examines why important parts of Wertheimer's experimental contributions to psychology may have been underrated or neglected by many contemporary psychologists.

In recent years, energy exchange has come to be accepted as the causative agent in accidental injuries. This paper focuses on two fundamental characteristics of accidental workplace injuries, their frequency, and their severity. I propose that the frequency of injuries is determined largely by the nature of the interactions between workers and production processes, while the severity of the occurring injuries will be more strongly affected by the maximum possible harm the production process can cause. Other aspects of the design of the production process may also affect the severity of injuries. Using aggregate national data for manufacturing industries in the US for 1972, the rate of injuries per 100 employees per year and the average number of lost work days per injury (a common measure of severity) were regressed against a number of econometric variables. Eighty percent of the variation in injury frequency rates among 61 industries was explained by seven variables. Among them were the rate of new hires, the productivity of energy and of labor, the average hourly wage, and the percentage of the workforce that was unionized. Four variables explained 69% of the variation in the severity of injuries among industries. Nearly half of this effect was caused by just one variable, the amount of energy consumed per worker. These results provide tentative confirmation for the models of injury frequency and severity that were proposed, and suggest the need for another study using less aggregated data.

"This paper presents and tests a regression-based model of black interstate migration. Explanatory variables include characteristics of origins and destinations, distance, and two migrant stock measures. The model is tested using black interstate migration flows published by the U.S. Bureau of the Census for 1965-70 and 1975-80." The emphasis is on the determinants of black migration, particularly for the period 1975-1980., (excerpt)

"This paper examines the impact of age on migration by providing estimates of identically specified migration equations for each of six age groups. Hypothesized effects of age on the relative importance of various explanatory variables are developed from a model viewing migration as an investment decision." This model is then tested empirically using U.S. data on inter-regional migration between 1965 and 1970. "The effects of economic opportunity differentials on migration are found to decline sharply with age. Lagged migration, the 'friends and relatives effect,' is found to be the most significant explanatory variable in all age group equations. Past migration is the only variable found to significantly influence the migration of persons over 65.", (excerpt)