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1.  Educational treasures in Radiology: A free online program for Radiology Boards preparation 
Purpose
An objective tool is desired, which optimally prepares for Radiology boards examination. Such program should prepare examinees with pertinent radiological contents and simulations as expected in the real examination.
Background
Many countries require written boards examinations for Radiology certification eligibility. No objective measure exists to tell if the examinee is ready to pass the exam or not. Time pressure and computer environment might be unfamiliar to examinees. Traditional preparation lectures don't simulate the "real" Radiology exam because they don't provide the special environment with multiple choice questions and timing.
Materials and Methods
This online program consists of 4 parts. The entry section allows to create questions with additional fields for comprehensive information. Sections include Pediatrics/Mammography/GI/IR/Nucs/Thoracic/Musculoskeletal/GU/Neuro/Ultrasound/Cardiac/OB/GYN and Miscellaneous. Experienced radiologists and educators evaluate and release/delete these entries in the administrator section. In the exam section users can create (un)timed customized exams for individual needs and learning pace. Exams can either include all sections or only specific sections to gear learning towards areas with weaker performance. Comprehensive statistics unveil the user's strengths and weaknesses to help focussing on "weak" areas. In the search section a comprehensive search and review can be performed by searching the entire database for keywords/topics or only searching within specific sections.
Conclusion
www.RadiologyBoards.org is a new working concept of Radiology boards preparation to detect and improve the examinee's weaknesses and finally to increase the examinee's confidence level for the final exam. It is beneficial for Radiology residents and also board certified radiologists to refresh/maintain radiological knowledge.
doi:10.3941/jrcr.v5i2.732
PMCID: PMC3303428  PMID: 22470779
Radiology boards; Radiology exam; exam preparation; Radiology examination
2.  DNA motif alignment by evolving a population of Markov chains 
BMC Bioinformatics  2009;10(Suppl 1):S13.
Background
Deciphering cis-regulatory elements or de novo motif-finding in genomes still remains elusive although much algorithmic effort has been expended. The Markov chain Monte Carlo (MCMC) method such as Gibbs motif samplers has been widely employed to solve the de novo motif-finding problem through sequence local alignment. Nonetheless, the MCMC-based motif samplers still suffer from local maxima like EM.
Therefore, as a prerequisite for finding good local alignments, these motif algorithms are often independently run a multitude of times, but without information exchange between different chains. Hence it would be worth a new algorithm design enabling such information exchange.
Results
This paper presents a novel motif-finding algorithm by evolving a population of Markov chains with information exchange (PMC), each of which is initialized as a random alignment and run by the Metropolis-Hastings sampler (MHS). It is progressively updated through a series of local alignments stochastically sampled. Explicitly, the PMC motif algorithm performs stochastic sampling as specified by a population-based proposal distribution rather than individual ones, and adaptively evolves the population as a whole towards a global maximum. The alignment information exchange is accomplished by taking advantage of the pooled motif site distributions. A distinct method for running multiple independent Markov chains (IMC) without information exchange, or dubbed as the IMC motif algorithm, is also devised to compare with its PMC counterpart.
Conclusion
Experimental studies demonstrate that the performance could be improved if pooled information were used to run a population of motif samplers. The new PMC algorithm was able to improve the convergence and outperformed other popular algorithms tested using simulated and biological motif sequences.
doi:10.1186/1471-2105-10-S1-S13
PMCID: PMC2648755  PMID: 19208112
3.  Evolving Concepts Related to Achieving Benefit Sharing for Custodians of Traditional Knowledge* 
In the context of evolving intellectual property law, defining ownership of traditional knowledge can be challenging when claims of origin are conflicting and requires accepting parameters of how uniqueness is defined and patent law is applied to protect this information. For purposes of this paper, the complexities of evolving benefit sharing for custodians of traditional knowledge are discussed in relationship to the use of medicinal plants. Parameters of ownership can vary not only by the perception of individuals that lay claim to the information but also by international, regional and national laws that govern how benefits should be fairly appropriated. Examples are provided to exemplify the wide variation that presently exists in this evolving process with illustrations of how this information, novel or otherwise, can be utilized to optimize its commercial worth.
PMCID: PMC2816506  PMID: 20161913
Ethnobotany; traditional knowledge; trade marks; patents
4.  Objectivity and ethics in environmental health science. 
Environmental Health Perspectives  2003;111(14):1809-1818.
During the past several decades, philosophers of science and scientists themselves have become increasingly aware of the complex ways in which scientific knowledge is shaped by its social context. This awareness has called into question traditional notions of objectivity. Working scientists need an understanding of their own practice that avoids the naïve myth that science can become objective by avoiding social influences as well as the reductionist view that its content is determined simply by economic interests. A nuanced perspective on this process can improve research ethics and increase the capacity of science to contribute to equitable public policy, especially in areas such as environmental and occupational health, which have direct implications for profits, regulation, legal responsibility, and social justice. I discuss research into health effects of the 1979 accident at Three Mile Island near Harrisburg, Pennsylvania, USA, as an example of how scientific explanations are shaped by social concepts, norms, and preconceptions. I describe how a scientific practice that developed under the influence of medical and nuclear physics interacted with observations made by exposed community members to affect research questions, the interpretation of evidence, inferences about biological mechanisms in disease causation, and the use of evidence in litigation. By considering the history and philosophy of their disciplines, practicing researchers can increase the rigor, objectivity, and social responsibility of environmental health science.
PMCID: PMC1241729  PMID: 14594636
5.  Ability of laboratory methods to predict in-use efficacy of antimicrobial preservatives in an experimental cosmetic. 
Applied and Environmental Microbiology  1994;60(12):4553-4558.
The abilities of nine antimicrobial systems to preserve an experimental water-based cosmetic formulation were evaluated by six microbiological challenge tests: the U.S. Pharmacopeia test; the British Pharmacopeia test; the Cosmetic, Toiletry, and Fragrance Association test; the rapid screen test; the sequential challenge test; and the post-use test. The antimicrobial systems contained various combinations and amounts of two parabens and a quaternary compound in order to provide a broad range of preservation. The results obtained were compared with the abilities of the formulations to support maintenance and growth of microorganisms in microfloras obtained from human axilla areas and finger skin during an 8-week simulated in-use test. Without statistical analysis all of the tests predicted the results obtained with well-preserved or poorly preserved formulations. The rapid screen test was the best test for predicting differences at intermediate levels of preservation. Statistically, all of the tests were equivalent predictors of preservation efficacy in the in-use test (P = 0.05). At the P = 0.10 level, only the U.S. Pharmacopeia, British Pharmacopeia, rapid screen, Cosmetic, Toiletry, and Fragrance Association tests were significantly predictive. The results of prediction by a test, based on the preservative levels used, agreed well with the in-use test results (P = 0.01). A total of 20% of the formulations that contained excessive microbial levels contained human axilla microorganisms. The levels of preservation in failed products were similar to the levels of preservation in unused controls.
PMCID: PMC202018  PMID: 7811091
6.  A Molecular Portrait of Arabidopsis Meiosis 
Meiosis is essential for eukaryotic sexual reproduction and important for genetic diversity among individuals. Efforts during the last decade in Arabidopsis have greatly expanded our understanding of the molecular basis of plant meiosis, which has traditionally provided much information about the cytological description of meiosis. Through both forward genetic analysis of mutants with reduced fertility and reverse genetic studies of homologs of known meiotic genes, we now have a basic knowledge about genes important for meiotic recombination and its relationship to pairing and synapsis, critical processes that ensure proper homolog segregation. In addition, several genes affecting meiotic progression, spindle assembly, chromosome separation, and meiotic cytokinesis have also been uncovered and characterized. It is worth noting that Arabidopsis molecular genetic studies are also revealing secrets of meiosis that have not yet been recognized elsewhere among eukaryotes, including gene functions that might be unique to plants and those that are potentially shared with animals and fungi. As we enter the post-genomics era of plant biology, there is no doubt that the next ten years will see an even greater number of discoveries in this important area of plant development and cell biology.
Abbreviations: DAPI, 4′,6-diamidino-2-phenylindole; DSB, double strand break; DSBR, double strand break repair; SC, synaptonemal complex; TEM, transmission electron microscopy
doi:10.1199/tab.0095
PMCID: PMC3243380  PMID: 22303228
pairing; recombination; synapsis; crossover formation; interference; spindle assembly
7.  Evaluating the Risk of Re-identification of Patients from Hospital Prescription Records 
Background:
Pharmacies often provide prescription records to private research firms, on the assumption that these records are de-identified (i.e., identifying information has been removed). However, concerns have been expressed about the potential that patients can be re-identified from such records. Recently, a large private research firm requested prescription records from the Children’s Hospital of Eastern Ontario (CHEO), as part of a larger effort to develop a database of hospital prescription records across Canada.
Objective:
To evaluate the ability to re-identify patients from CHEO’S prescription records and to determine ways to appropriately de-identify the data if the risk was too high.
Methods:
The risk of re-identification was assessed for 18 months’ worth of prescription data. De-identification algorithms were developed to reduce the risk to an acceptable level while maintaining the quality of the data.
Results:
The probability of patients being re-identified from the original variables and data set requested by the private research firm was deemed quite high. A new de-identified record layout was developed, which had an acceptable level of re-identification risk. The new approach involved replacing the admission and discharge dates with the quarter and year of admission and the length of stay in days, reporting the patient’s age in weeks, and including only the first character of the patient’s postal code. Additional requirements were included in the data-sharing agreement with the private research firm (e.g., audit requirements and a protocol for notification of a breach of privacy).
Conclusions:
Without a formal analysis of the risk of re-identification, assurances of data anonymity may not be accurate. A formal risk analysis at one hospital produced a clinically relevant data set that also protects patient privacy and allows the hospital pharmacy to explicitly manage the risks of breach of patient privacy.
PMCID: PMC2826964  PMID: 22478909
privavy; de-identification; re-identification risk; data anonymity; secondary use of data; vie privée; dépersonnalisation; risque de reconstitution de l’identité; anonymat des données; utilisation secondaire des données
8.  Treasure or White Elephant? * 
Small libraries have problems with accepting gifts of older material. Older textbooks are probably worthless, while real rarities may belong elsewhere. The usefulness of the book to the collection must be considered. While textbooks age, monographs have a longer life, and history and biography last forever. Ephemeral pamphlets have historical value. Condition of the book also affects its value. A library should always keep publications about its own institution.
Suggestions are given on whether to discard or sell, with warnings about pitfalls in selling.
PMCID: PMC197472  PMID: 5424515
9.  Non-coding RNA and Antisense RNA. Nature's Trash or Treasure? 
Biochimie  2011;93(11):1922-1927.
Although control of cellular function has classically been considered the responsibility of proteins, research over the last decade has elucidated many roles for RNA in regulation of not only the proteins that control cellular functions but also for the cellular functions themselves. In parallel to this advancement in knowledge about the regulatory roles of RNA there has been an explosion of knowledge about the role that epigenetics plays in controlling not only long-term cellular fate but also the short-term regulatory control of genes. Of particular interest is the crossover between these two worlds, a world where RNA can act out its part and subsequently elicit chromatin modifications that alter cellular function. Two main categories of RNA are examined here, non-coding RNA and antisense RNA both of which perform vital functions in controlling numerous genes, proteins and RNA itself. As the activities of non-coding and antisense RNA in both normal and aberrant cellular function are elucidated, so does the number of possible targets for pharmacopeic intervention.
doi:10.1016/j.biochi.2011.07.031
PMCID: PMC3195647  PMID: 21843589
antisense RNA; non-coding RNA; epigenetic; transcription; gene silencing
10.  Phylogenetic biodiversity assessment based on systematic nomenclature 
Biodiversity assessment demands objective measures, because ultimately conservation decisions must prioritize the use of limited resources for preserving taxa. The most general framework for the objective assessment of conservation worth are those that assess evolutionary distinctiveness, e.g. Genetic (Crozier 1992) and Phylogenetic Diversity (Faith 1992), and Evolutionary History (Nee & May 1997). These measures all attempt to assess the conservation worth of any scheme based on how much of the encompassing phylogeny of organisms is preserved. However, their general applicability is limited by the small proportion of taxa that have been reliably placed in a phylogeny. Given that phylogenizaton of many interesting taxa or important is unlikely to occur soon, we present a framework for using taxonomy as a reasonable surrogate for phylogeny. Combining this framework with exhaustive searches for combinations of sites containing maximal diversity, we provide a proof-of-concept for assessing conservation schemes for systematized but un-phylogenised taxa spread over a series of sites. This is illustrated with data from four studies, on North Queensland flightless insects (Yeates et al. 2002), ants from a Florida Transect (Lubertazzi & Tschinkel 2003), New England bog ants (Gotelli & Ellison 2002) and a simulated distribution of the known New Zealand Lepidosauria (Daugherty et al. 1994). The results support this approach, indicating that species, genus and site numbers predict evolutionary history, to a degree depending on the size of the data set.
PMCID: PMC2658867  PMID: 19325850
Evolutionary history; phylogenetic diversity; genetic diversity; biodiversity; phylogeny; systematic nomenclature
11.  The treasure trove of yeast genera and species described by Johannes van der Walt (1925–2011) 
IMA Fungus  2012;3(2):179-187.
Yeast taxonomy and systematics have in recent years been dealt with intensively primarily by a small group of individual researchers with particular expertise. Amongst these was Johannes P. van der Walt, who had a major role in shaping our current understanding of yeast biodiversity and taxonomy. Van der Walt based his taxonomic studies not only on available cultures, but also by going into the field to isolate yeasts from various substrates. This pioneering work led to the discovery of many new genera and species, which were deposited in the Centraalbureau voor Schimmelcultures (CBS) collections for future studies in taxonomy, genomics, and industrial uses. These treasures collected during more than 60 years provide an outstanding legacy to the yeast community and will continue to exist in his absence. This contribution provides a comprehensive overview of the current nomenclatural and taxonomic status of the yeast genera and species introduced by van der Walt during his career.
doi:10.5598/imafungus.2012.03.02.10
PMCID: PMC3539321  PMID: 23355971
South Africa; biodiversity; taxonomy
12.  SNP and Mutation Data on the Web – Hidden Treasures for Uncovering 
SNP data has grown exponentially over the last two years, SNP database evolution has matched this growth, as initial development of several independent SNP databases has given way to one central SNP database, dbSNP. Other SNP databases have instead evolved to complement this central database by providing gene specific focus and an increased level of curation and analysis on subsets of data, derived from the central data set. By contrast, human mutation data, which has been collected over many years, is still stored in disparate sources, although moves are afoot to move to a similar central database. These developments are timely, human mutation and polymorphism data both hold complementary keys to a better understanding of how genes function and malfunction in disease. The impending availability of a complete human genome presents us with an ideal framework to integrate both these forms of data, as our understanding of the mechanisms of disease increase, the full genomic context of variation may become increasingly significant.
doi:10.1002/cfg.131
PMCID: PMC2447234  PMID: 18628874
13.  Educational treasures in Radiology: Radiolopolis – an international Radiology community 
This article focuses on a relatively new concept in the Internet: “Social networking” and especially on one program that successfully found a unique way to provide a social network for Radiology: Radiolopolis. Radiolopolis (www.Radiolopolis.com) is an international Radiology network to promote education, research and clinical practice in Radiology. What makes this Radiology community unique and special is that the founders of Radiolopolis implemented multiple educational and clinical/practical programs which have been developed over the past years.
doi:10.3941/jrcr.v3i9.256
PMCID: PMC3303334  PMID: 22470687
Radiology community; Radiology network; social networking; Radiology education; research; training; clinical practice; information exchange; teaching; Radiolopolis
14.  Barley grain for ruminants: A global treasure or tragedy 
Barley grain (Hordeum vulgare L.) is characterized by a thick fibrous coat, a high level of ß-glucans and simply-arranged starch granules. World production of barley is about 30 % of that of corn. In comparison with corn, barley has more protein, methionine, lysine, cysteine and tryptophan. For ruminants, barley is the third most readily degradable cereal behind oats and wheat. Due to its more rapid starch fermentation rate compared with corn, barley also provides a more synchronous release of energy and nitrogen, thereby improving microbial nutrient assimilation. As a result, feeding barley can reduce the need for feeding protected protein sources. However, this benefit is only realized if rumen acidity is maintained within an optimal range (e.g., > 5.8 to 6.0); below this range, microbial maintenance requirements and wastage increase. With a low pH, microbial endotoxines cause pro-inflammatory responses that can weaken immunity and shorten animal longevity. Thus, mismanagement in barley processing and feeding may make a tragedy from this treasure or pearl of cereal grains. Steam-rolling of barley may improve feed efficiency and post-rumen starch digestion. However, it is doubtful if such processing can improve milk production and feed intake. Due to the need to process barley less extensively than other cereals (as long as the pericarp is broken), consistent and global standards for feeding and processing barley could be feasibly established. In high-starch diets, barley feeding reduces the need for capacious small intestinal starch assimilation, subsequently reducing hindgut starch use and fecal nutrient loss. With its nutritional exclusivities underlined, barley use will be a factual art that can either matchlessly profit or harm rumen microbes, cattle production, farm economics and the environment.
doi:10.1186/2049-1891-3-22
PMCID: PMC3436651  PMID: 22958810
Barley; Cereal; Ruminant; Starch; Treasure
15.  Alkaptonuria: Leading to the Treasure in Exceptions 
JIMD Reports  2011;5:49-57.
The brilliant geneticist, William Bateson, a formidable English experimentalist, was the first to recognize the nature of the “inborn” in Archibald Garrod’s errors of metabolism. Bateson’s advice to young scientists: “Treasure your exceptions!” summarizes much of the vigorous empiricism associated with the study of rare disorders.
The first inborn error of metabolism to be so recognized was alkaptonuria, and it is only recently that a proper understanding of this condition as a disease, rather than a biochemical curiosity, has emerged. Abnormal excretion of the reactive tyrosine metabolite, homogentisic acid, not only provides a tangible biomarker of alkaptonuria, but also a focus for detailed mechanistic understanding.
Currently, there is no proven treatment for alkaptonuria but emergence of orphan drug legislation internationally has promoted the licensing of nitisinone (Orfadin™) for an equally rare disorder of tyrosine metabolism – hereditary tyrosinaemia type 1. Nitisinone, a triketone competitive inhibitor of a proximal step leading to the formation of homogentisic acid, has potent therapeutic effects in hereditary tyrosinemia and rapidly ameliorates the primary biochemical abnormality in patients with alkaptonuria.
Here, we discuss the context in which nitisinone should be further explored for the treatment of alkaptonuria. This exceptional disease is a paradigm case, which opens up unusual opportunities for basic and applied research. In modern times, it also shows how the conflation of orphan drug legislation and the emerging power and commitment of patient organizations can synergize effectively to advance basic research and therapeutic development in ultra-orphan diseases.
doi:10.1007/8904_2011_93
PMCID: PMC3509923  PMID: 23430917
16.  Contribution of serum IL-4 and IgE to the early prediction of horse serum allergies in guinea pigs 
Asia Pacific Allergy  2012;2(4):264-268.
Background
Horse serum (HS) was a strong allergen for xenogeneic animals. However, the methods of test for allergen didn't authorized in Pharmacopeia of the United States, European Pharmacopeia, Japanese Pharmacopeia and British Pharmacopeia. Thus, new methods of test for allergen are required to control drug allergy.
Objective
To propose a new method for detecting horse serum induced allergic reactions of guinea pigs earlier.
Methods
Guinea pigs were sensitized successively by injecting different concentration of HS intravenously once a day for three times, serum level of IL-4 and total IgE were detected by method of enzyme linked immunosorbent assay (ELISA) before guinea pigs were challenged by injecting HS intravenously only once, and the results were compared with routine method of sensitization by injecting HS intraperitoneally every other day for three times.
Results
Serum level of IL-4 and total IgE increased significantly before guinea pigs were challenged, either in day 8 after intravenous sensitization (10%HS, 0.5 mL) or in day 14 and day 21 after intraperitoneal sensitization (10%HS, 0.5 mL), and allergic reactions occurred in all guinea pigs after challenged by injecting HS (10%, 1.0 mL) only once.
Conclusion
It provides a new way to predict whether HS or other drugs can provoke allergic reactions earlier by detecting the serum level of IL-4 and total IgE in d8 after intravenous sensitization, this has a good application value in drug emergency test.
doi:10.5415/apallergy.2012.2.4.264
PMCID: PMC3486971  PMID: 23130332
IL-4; Total IgE; Horse serum; Allergic reactions; Detection
17.  CALCULATING THE COST OF ACTING IN FRONTAL CORTEX 
In order to be able to make informed and successful decisions, it is vital to be able to evaluate whether the expected benefits of a course of action make it worth tolerating the costs incurred to obtain them. The frontal lobe has been implicated in several aspects of goal-directed action selection, social interaction and optimal choice behavior. However, its exact contribution has remained elusive. Here, we discuss a series of studies in rats and primates examining the effect of discrete lesions on different aspects of cost-benefit decision making. Rats with excitotoxic lesions of the anterior cingulate cortex became less willing to invest effort for reward but showed no change when having to tolerate delays. Orbitofrontal cortex-lesioned rats, by contrast, became more impulsive, yet were just as prepared as normal animals to expend energy to obtain reward. The sulcal region of primate anterior cingulate cortex was also shown to be essential for dynamically integrating over time the recent history of choices and outcomes. Selecting a particular course of action may also come at the expense of gathering important information about other individuals. Evaluating social information when deciding whether to respond was demonstrated to be a function of the anterior cingulate gyrus. Taken together, this indicates that there may be dissociable pathways in the frontal lobe for managing different types of response cost and for gathering social information.
doi:10.1196/annals.1390.009
PMCID: PMC2519032  PMID: 17360802
Anterior cingulate cortex; Orbitofrontal cortex; Decision making; Effort; Delay; Risk; Social
18.  Hormonal Regulation Of Hepatic Glucose Production In Health And Disease 
Cell metabolism  2011;14(1):9-19.
We review mechanisms that regulate production of glucose by the liver, focusing on areas of budding consensus, and endeavoring to provide a candid assessment of lingering controversies. We also attempt to reconcile data from tracer studies in humans and large animals with the growing compilation of mouse knockouts that display changes in glucose production. A clinical hallmark of diabetes, excessive glucose production remains key to its treatment. Hence, we attempt to integrate emerging pathways into the broader goal to rejuvenate the staid anti-diabetic pharmacopeia.
doi:10.1016/j.cmet.2011.06.003
PMCID: PMC3131084  PMID: 21723500
19.  To what extent can traditional medicine contribute a complementary or alternative solution to malaria control programmes? 
Malaria Journal  2011;10(Suppl 1):S6.
Recent studies on traditional medicine (TM) have begun to change perspectives on TM effects and its role in the health of various populations. The safety and effectiveness of some TMs have been studied, paving the way to better collaboration between modern and traditional systems. Traditional medicines still remain a largely untapped health resource: they are not only sources of new leads for drug discoveries, but can also provide lessons and novel approaches that may have direct public-health and economic impact. To optimize such impact, several interventions have been suggested, including recognition of TM's economic and medical worth at academic and health policy levels; establishing working relationships with those prescribing TM; providing evidence for safety and effectiveness of local TM through appropriate studies with malaria patients; spreading results for clinical recommendations and health policy development; implementing and evaluating results of new health policies that officially integrate TM.
doi:10.1186/1475-2875-10-S1-S6
PMCID: PMC3059464  PMID: 21411017
20.  On Immunologists and Microbiologists: Ground Zero in the Battle for Interdisciplinary Knowledge 
mBio  2010;1(5):e00260-10.
The individual disciplines of microbiology and immunology are exploding with new information necessary for understanding host-pathogen relationships, infectious diseases, cancer, and autoimmunity. Because of overlapping scientific interests, immunologists and microbiologists often share common academic affiliations. The coexistence is uneasy. Significant problems arise because the groups have evolved different intellectual traditions. Pressures are intensified by sporadic changes in perceptions of their relative worth. As the mixing of microbiologists and immunologists can be likened to ground zero in the fight for interdisciplinary knowledge, it is useful, at this time of escalating data acquisition and growing appreciation for multidisciplinary research, to examine their histories, the challenges to amalgamation, and the advantages of their association for the advancement of knowledge and the delivery of protection against disease. The exploration supports a recommitment to integration of the disciplines and a proposal to facilitate this by inclusion of expertise bridging the areas.
doi:10.1128/mBio.00260-10
PMCID: PMC2975366  PMID: 21103040
21.  Nuremberg and Tuskegee: lessons for contemporary American medicine. 
The activities of German doctors during the Nazi regime are well known and documented. They include efforts at eugenic sterilization and euthanasia, gruesome medical experimentation, and contributions to genocide. The German medical profession embraced the Nazi ideology of racial superiority. Nazi doctors enthusiastically perverted traditional medical mores of viewing each patient as a full individual towards a misguided sense of protecting the racial well-being of the nation from the perceived threat of certain groups of people. Similarly, some 20th-century American physicians engaged in activities prompted by a misguided sense of patients' worth as individuals. This essay will examine the ethical problems of Nazi medicine and ethical missteps in the United States in the context of challenges for contemporary physicians, particularly the way in which we refer to our patients.
PMCID: PMC2594827  PMID: 14717481
22.  The Malpractice Feud 
The propriety of an immediate resolution of the malpractice feud rests on the strong thesis that law and medicine cannot be mutually exclusive if both shall continue to remain true to their traditional pledges. The common need to serve, primarily, the human being and, secondarily, the client or patient is a sufficient basis for much compromise. It should always be remembered that if there were no life there would be no rights to defend; nor would life be worth its very name, if legal rights were nil.
This paper assesses some of the basic differences between law and medicine, identifies the historical and recent events that precipitated the current malpractice feud, and offers some ameliorative measures for resolving the uneasy state.
PMCID: PMC2552646  PMID: 7218368
23.  Analysis of 72-Hour Sterility of Common Pediatric Continuous Intravenous Infusions 
OBJECTIVES
Patient morbidity and mortality associated with contaminated and improperly prepared sterile products has captured national attention. In response, both the United States Pharmacopeia (USP) and Centers for Disease Control (CDC) have published recommendations in an effort to minimize the risk of infection. While the CDC recommends that administration sets are not changed more frequently than every 72 hours, the USP recommends a maximum beyond use date of 48 hours. Neither organization provides specific guidance on expiration dating once the intravenous drug is dispensed. Likewise, neither addresses the length of time that a bag containing medication for continuous infusion may hang once administration to the patient has begun. We evaluated the sterility of medications that are commonly administered by continuous infusion to pediatric patients. Because frequent manipulation of infusion and administration sets may predispose the patient to adverse events, we evaluated sterility for extended beyond use dating up to 72 hours.
METHODS
Thirty-five common intravenous (IV) continuous infusions using 94 standard concentrations and diluents were identified. IV solutions were mixed using sterile technique in the laminar flow hood in accordance with USP guidelines. Medications were excluded for short stability, short durations of use or high cost. A sample from each solution was tested for contamination or bacterial growth at 72 hours. Any visible discoloration suggesting physical instability was also evaluated.
RESULTS
None of the syringes or chambers resulted in contamination, bacterial growth or discoloration after 72 hours.
CONCLUSIONS
This study provides sufficient data that these compounded sterile products may be stored using a beyond use date up to 72 hours for a number of commonly used continuous IV infusions in pediatric patients. In our institution, this allows for a more convenient and consistent change of both administration sets and continuous infusions at 72 hours to potentially minimize adverse events, workload and cost.
doi:10.5863/1551-6776-14.1.25
PMCID: PMC3461993  PMID: 23055888
continuous infusions; expiration; pediatric; sterility
24.  Tales from the New Frontier: Pioneers' Experiences with Consumer-Driven Health Care 
Health Services Research  2004;39(4 Pt 2):1071-1090.
Objective
To conduct site visits to study the early experiences of firms offering consumer-driven health care (CDHC) plans to their employees and firms that provide CDHC products.
Data Sources/Study Setting
A convenience sample of three firms offering CDHC products to their employees, one of which is also a large insurer, and one firm offering an early CDHC product to employers.
Study Design
We conducted onsite interviews of four companies during the spring and summer of 2003. These four cases were not selected randomly. We contacted organizations that already had a consumer-driven plan in place by January 2002 so as to provide a complete year's worth of experience with CDHC.
Principal Findings
The experience of the companies we visited indicated that favorable selection tends to result when a CDHC plan is introduced alongside traditional preferred provider organization (PPO) and health maintenance organization (HMO) plan offerings. Two sites demonstrated substantial cost-savings. Our case studies also indicate that the more mundane aspects of health care benefits are still crucial under CDHC. The size of the provider network accessible through the CDHC plan was critical, as was the role of premium contributions in the benefit design. Also, companies highlighted the importance of educating employees about new CDHC products: employees who understood the product were more likely to enroll.
Conclusions
Our site visits suggest the peril (risk selection) and the promise (cost savings) of CDHC. At this point there is still far more that we do not know about CDHC than we do know. Little is known about the extent to which CDHC changes people's behavior, the extent to which quality of care is affected by CDHC, and whether web-based information and tools actually make patients become better consumers.
doi:10.1111/j.1475-6773.2004.00274.x
PMCID: PMC1361054  PMID: 15230912
Employer-sponsored health insurance; health reimbursement arrangement; cost sharing
25.  The cosmological model of eternal inflation and the transition from chance to biological evolution in the history of life 
Biology Direct  2007;2:15.
Background
Recent developments in cosmology radically change the conception of the universe as well as the very notions of "probable" and "possible". The model of eternal inflation implies that all macroscopic histories permitted by laws of physics are repeated an infinite number of times in the infinite multiverse. In contrast to the traditional cosmological models of a single, finite universe, this worldview provides for the origin of an infinite number of complex systems by chance, even as the probability of complexity emerging in any given region of the multiverse is extremely low. This change in perspective has profound implications for the history of any phenomenon, and life on earth cannot be an exception.
Hypothesis
Origin of life is a chicken and egg problem: for biological evolution that is governed, primarily, by natural selection, to take off, efficient systems for replication and translation are required, but even barebones cores of these systems appear to be products of extensive selection. The currently favored (partial) solution is an RNA world without proteins in which replication is catalyzed by ribozymes and which serves as the cradle for the translation system. However, the RNA world faces its own hard problems as ribozyme-catalyzed RNA replication remains a hypothesis and the selective pressures behind the origin of translation remain mysterious. Eternal inflation offers a viable alternative that is untenable in a finite universe, i.e., that a coupled system of translation and replication emerged by chance, and became the breakthrough stage from which biological evolution, centered around Darwinian selection, took off. A corollary of this hypothesis is that an RNA world, as a diverse population of replicating RNA molecules, might have never existed. In this model, the stage for Darwinian selection is set by anthropic selection of complex systems that rarely but inevitably emerge by chance in the infinite universe (multiverse).
Conclusion
The plausibility of different models for the origin of life on earth directly depends on the adopted cosmological scenario. In an infinite universe (multiverse), emergence of highly complex systems by chance is inevitable. Therefore, under this cosmology, an entity as complex as a coupled translation-replication system should be considered a viable breakthrough stage for the onset of biological evolution.
Reviewers
This article was reviewed by Eric Bapteste, David Krakauer, Sergei Maslov, and Itai Yanai.
doi:10.1186/1745-6150-2-15
PMCID: PMC1892545  PMID: 17540027

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