Olfactory subsystems in the peripheral olfactory organ of anuran amphibians.

Anuran amphibians (frogs and toads) typically have a complex life cycle, involving aquatic larvae that metamorphose to semi-terrestrial juveniles and adults. However, the anuran olfactory system is best known in Xenopus laevis, an animal with secondarily aquatic adults. The larval olfactory organ contains two distinct sensory epithelia: the olfactory epithelium (OE) and vomeronasal organ (VNO). The adult organ contains three: the OE, the VNO, and a "middle cavity" epithelium (MCE), each in its own chamber. The sensory epithelia of Xenopus larvae have overlapping sensory neuron morphology (ciliated or microvillus) and olfactory receptor gene expression. The MCE of adults closely resembles the OE of larvae, and senses waterborne odorants; the adult OE is distinct and senses airborne odorants. Olfactory subsystems in other (non-pipid) anurans are diverse. Many anuran larvae show a patch of olfactory epithelium exposed in the buccal cavity (bOE), associated with a grazing feeding mode. And other anuran adults do not have a sensory MCE, but many have a distinct patch of epithelium adjacent to the OE, the recessus olfactorius (RO), which senses waterborne odorants. Olfaction plays a wide variety of roles in the life of larval and adult anurans, and some progress has been made in identifying relevant odorants, including pheromones and feeding cues. Increased knowledge of the diversity of olfactory structure, of odorant receptor expression patterns, and of factors that affect the access of odorants to sensory epithelia will enable us to better understand the adaptation of the anuran olfactory system to aquatic and terrestrial environments.

TRAQ Changes: Improving the Measurement of Transition Readiness by the Transition Readiness Assessment Questionnaire.

OBJECTIVE: The purpose of the current study was improving the measurement precision of the Transition Readiness Assessment Questionnaire (TRAQ 5.0-20 item) in order to gain better decimation of transition readiness skills across the 5 Stages of Change-from Precontemplation to Mastery. METHODS: In stage 1, starting with the TRAQ 5.0 20-item, 5 domain subscale questionnaire, we eliminated the five lowest discriminating items using Item response theory (IRT) in MPlus v7.4,which eliminated the domain subscale Managing Daily Activities, and we e added 15 more difficult and better discriminating items. We added items to both to the remaining 4 domain subscales and created a new domain subscale entitled Future Planning. The revised 30-item TRAQ was piloted among 386 youth between 16 and 24 years old (mean = 20 years; 54% female; 87% White). RESULTS: After examining the model fit, discrimination and difficulty coefficients, and modification indices, we eliminated 10 items and the new Future Planning domain subscale we eliminated. The resulting questionnaire has 4 domain subscales and 20 items. It exhibited good to excellent fit to the data, χ2(164) = 887.239, p < .001, CFI = 0.943, TLI = 0.93, RMSEA = 0.0942 (90% CI: 0.090, 0.114), WRMR = 1.111. All items have acceptable discrimination coefficients. Each of the 4 domain subscales have improved reliability as compared with the original TRAQ 5.0 20 item scale. CONCLUSIONS: The revised 20-itemTRAQ 6.0 has 4 domains subscales; Managing medications, keeping appointment, tracking health issues, and Talking with providers and has good construct validity as demonstrated by model fit. By adding more difficult items to the 4 resulting domain subscales, we have demonstrated improved item discrimination and difficulty, and therefore can better measure acquisition of transition readiness skills across the five stages of change from pre-contemplation to contemplation to initiation to action and finally to mastery.

A systematic review of transition readiness and transfer satisfaction measures for adolescents with chronic illness.

BACKGROUND: The transition from pediatric to adult health care can be challenging for adolescents with chronic illnesses. As a result, many adolescents are unable to transfer to adult health care successfully. Adequate measurement of transition readiness and transfer satisfaction with disease management is necessary in order to determine areas to target for intervention towards improving transfer outcomes. OBJECTIVES: This study aims to systematically review and critically appraise research on transition readiness and transfer satisfaction measures for adolescents with chronic illnesses as well as to assess the psychometric quality of these measures. METHODS: Electronic searches were conducted in MEDLINE, EMBASE, CINAHL, PsychINFO, ERIC, and ISI Web of Knowledge for transition readiness and transfer satisfaction measures for adolescents with chronic health conditions. Two reviewers independently selected articles for review and assessed methodological quality. RESULTS: In all, eight readiness and six satisfaction measures met the inclusion criteria, for a total of 14 studies, which were included in the final analysis. None of these measures have well-established evidence of reliability and validity. Most of the measures were developed ad hoc by the study investigators, with minimal to no evidence of reliability and/or validity using the Cohen criteria and COSMIN checklist. CONCLUSION: This research indicates a major gap in our knowledge of transitional care in this population, because there is currently no well-validated questionnaire that measures readiness for transfer to adult health care. Future research must focus on the development of well-validated transition readiness questionnaires, the validation of existing measures, and reaching consensus on outcomes of successful transfer.

Your business in court and at Federal agencies: 2011-2012.

FDA transparency effort continued, including the Secretary's adopting eight measures to improve access to Agency information and activities. A continuing problem was shortages of prescription drugs, which probably was enhanced by increased manufacturing recalls. FDA issued more device Guidances for regulatory clarity. Enforcement involving drugs and devices increased, including GMP and GLP enforcement and surveillance of internet claims. The Supreme Court decided generic drug manufacturers may cause the FDA to revise incorrectly listed use codes, and pharmaceutical detailers may not receive overtime payments. FDA initiated implementation of the Food Safety and Modernization Act, including two pilot tracking systems for supply chain tracing and to determine how quickly data can be gathered. The Agency issued guidance for new dietary supplements. FDA failed to impose graphic labeling requirements on the tobacco industry, but established it can regulate electronic cigarettes as tobacco. The Agency issued guidelines for the use of nanomaterials in cosmetics, and reviewed the effectiveness of sunscreen products. FDA is being given more authority over larger areas of the U.S. economy, but its resources are not increased proportionately. The pharmaceutical industry made major payments for alleged violations of the Drug Rebate Statute, Anti-Kickback Statute, Wholesale Price and Off-Label Use prohibitions. The government continues using the Responsible Corporate Officer doctrine to make company managers responsible for corporate conduct about which they had no knowledge. Companies should have a robust compliance program in effect. The FTC and the SEC continue their oversight activities, including SEC's enforcement of the Foreign Corrupt Practices Act. The defense of product liability litigation continues grappling with federal preemption of state laws.

Your business in court and at federal agencies: 2010 - 2011.

This year the government aggressively pursued Manufacturers under the enhanced provisions of the False Claims Act (FCA), as well as under the provisions of the Food, Drug and Cosmetics Act (FDCA). In addition, the government pursued actions against individual executives under the Responsible Corporate Officer Doctrine ("RCO Doctrine") because it does not believe sanctions against the companies provide sufficient deterrence to inappropriate behavior. Companies need to focus on implementing effective compliance programs in order to prevent the occurrence of allegedly improper activity. It should be noted that the existence of an effective program will not protect executives from liability under the RCO Doctrine if improper behavior takes place. The Food and Drug Administration's (FDA's) has undertaken a number of initiatives during the past year in an attempt to counter claims that its review processes for domestic products is driving the development of drugs and devices to overseas markets. The Agency also has improved its capacity to review products imported from overseas by undertaking initiatives with foreign agencies and stationing more FDA employees in foreign countries. The FDA increased the number of warning letters and other enforcement actions. The FDA added two new topics of enhanced authority during the year. One was an expansion of its regulatory authority over foods, and the second was new authority to regulate certain tobacco products. The former is being subjected to some review by the courts, and the scope of its authority over tobacco is the subject of ongoing major litigation. The Federal Trade Commission (FTC) and Securities and Exchange Commission (SEC) are unlikely to experience significant change regarding their regulation of Manufacturers. The FTC, as it has for many years, continues to try to prevent "reverse" payments to generic drug manufacturers by Innovator Manufacturers to diminish generic drug competition, and proposed legislation is before Congress. The SEC still appears focused on the Foreign Corporate Practices Act with respect to enforcement against pharmaceutical and device manufacturers. Federal preemption of State law continues to be a topic of concern, with Court's taking different positions on the effect of the various Supreme Court decisions made in the last two years.

Measuring the transition readiness of youth with special healthcare needs: validation of the TRAQ--Transition Readiness Assessment Questionnaire.

OBJECTIVE: The aim of this study was to develop the Transition Readiness Assessment Questionnaire (TRAQ), a measure of readiness for transition from pediatric to adult healthcare for youth with special health care needs (YSHCN). METHODS: We administered TRAQ to 192 YSHCN aged 16-26 years in three primary diagnostic categories, conducted factor analysis, and assessed differences in TRAQ scores by age, gender, race, and primary diagnosis type. RESULTS: Factor analysis identified two TRAQ domains with high internal consistency: Skills for Self-Management and Skills for Self-Advocacy. Each domain had high internal consistency. In multivariate regression models, older age and a primary diagnosis of an activity limiting physical condition were associated with higher scores in Self-Management, and female gender and a primary diagnosis of an activity limiting physical condition were associated with higher scores in Self-Advocacy. CONCLUSIONS: Our initial validation study suggests the TRAQ is a useful tool to assess transition readiness in YSHCN and to guide educational interventions by providers to support transition.

Your business in court: 2009-2010.

During this period, FDA focused considerable effort on its transparency initiative, which is likely to continue into the coming year, as well as continuing to ramp up its enforcement activities, as we predicted last year. The scope of the agency's ability to pre-empt state laws in product liability litigation involving pharmaceutical products still is developing post-Levine, and we are likely to see new decisions in the coming year. Fraud and abuse enforcement still is a major factor facing the industry, with the added threat of personal exposure to criminal sentences, fines and debarment from participation in federal and state programs under the Responsible Corporate Officer doctrine, or under the authorities exercised by the Department of Health and Human Services Office of the Inspector General. Consequently, it is increasingly important that senior corporate officers ensure active oversight of an effective compliance program which should mitigate these risks. The Federal Trade Commission continues to battle consumer fraud, particularly respecting weight loss programs, and it appears to be fighting a losing battle in its effort to prevent "reverse" payments to generic manufacturers by Innovator Manufacturers to delay the introduction of generics to the market. The Securities and Exchange Commission continues to be actively enforcing the Foreign Corrupt Practices Act. The Supreme Court gave shareholders more leeway in bringing stockholder suits in situations where a company conceals information that, if revealed, could have a negative effect on stock prices.

The ontogeny of the olfactory system in ceratophryid frogs (Anura, Ceratophryidae).

The aquatic-to-terrestrial shift in the life cycle of most anurans suggests that the differences between the larval and adult morphology of the nose are required for sensory function in two media with different physical characteristics. However, a better controlled test of specialization to medium is to compare adult stages of terrestrial frogs with those that remain fully aquatic as adults. The Ceratophryidae is a monophyletic group of neotropical frogs whose diversification from a common terrestrial ancestor gave rise to both terrestrial (Ceratophrys, Chacophrys) and aquatic (Lepidobatrachus) adults. So, ceratophryids represent an excellent model to analyze the morphology and possible changes related to a secondary aquatic life. We describe the histomorphology of the nose during the ontogeny of the Ceratophryidae, paying particular attention to the condition in adult stages of the recessus olfactorius (a small area of olfactory epithelium that appears to be used for aquatic olfaction) and the eminentia olfactoria (a raised ridge on the floor of the principal cavity correlated with terrestrial olfaction). The species examined (Ceratophrys cranwelli, Chacophrys pierottii, Lepidobatrachus laevis, and L. llanensis) share a common larval olfactory organ composed by the principal cavity, the vomeronasal organ and the lateral appendix. At postmetamorphic stages, ceratophryids present a common morphology of the nose with the principal, middle, and inferior cavities with characteristics similar to other neobatrachians at the end of metamorphosis. However, in advanced adult stages, Lepidobatrachus laevis presents a recessus olfactorius with a heightened (peramorphic) development and a rudimentary (paedomorphic) eminentia olfactoria. Thus, the adult nose in Lepidobatrachus laevis arises from a common developmental 'terrestrial' pathway up to postmetamorphic stages, when its ontogeny leads to a distinctive morphology related to the evolutionarily derived, secondarily aquatic life of adults of this lineage.

Disease associated with integumentary and cloacal parasites in tadpoles of northern red-legged frog Rana aurora aurora.

A total of 6830 northern red-legged frog Rana aurora aurora tadpoles were examined under a dissecting microscope for oral disc, integumentary, and cloacal abnormalities in 13 ponds in and near Redwood National Park in northern California. Of these, 163 tadpoles were collected for histopathological investigation, including 115 randomly collected individuals, 38 collected with oral disc abnormalities, and 10 collected due to severe morbidity of unknown etiology. The tadpoles were infected with 8 parasites, including Batrachochytrium dendrobatidis (the amphibian chytrid), trematodes, leeches, and protozoa. Chytridiomycosis was detected at an overall prevalence of 6.4%, but prevalence was higher in tadpoles with oral disc lesions than in those with normal oral discs (43.5% versus 6.1%). Interestingly, infection was associated with some environmental and co-infection risk factors. Individual tadpoles possessed 0 to 5 species of parasites in varying intensities. Apiosoma sp. was the most prevalent (66%) and widespread. Tadpoles infected with B. dendrobatidis had a lower diversity of oral parasites than those uninfected. During the field portion of the study, a large number (approximately 500) of moribund and dead tadpoles was seen occurring at multiple locations within and surrounding Redwood National Park. Ten animals were collected for histological examination and a diverse protozoal infection was discovered, including some known pathogens of fish. This study is the first reporting parasitism and disease in natural populations of northern red-legged frogs.

Quantitative comparative analysis of the nasal chemosensory organs of anurans during larval development and metamorphosis highlights the relative importance of chemosensory subsystems in the group.

The anuran peripheral olfactory system is composed of a number of subsystems, represented by distinct neuroepithelia. These include the main olfactory epithelium and vomeronasal organ (found in most tetrapods) and three specialized epithelia of anurans: the buccal-exposed olfactory epithelium of larvae, and the olfactory recess and middle chamber epithelium of postmetamorphic animals. To better characterize the developmental changes in these subsystems across the life cycle, morphometric changes of the nasal chemosensory organs during larval development and metamorphosis were analyzed in three different anuran species (Rhinella arenarum, Hypsiboas pulchellus, and Xenopus laevis). We calculated the volume of the nasal chemosensory organs by measuring the neuroepithelial area from serial histological sections at four different stages. In larvae, the vomeronasal organ was relatively reduced in R. arenarum compared with the other two species; the buccal-exposed olfactory epithelium was absent in X. laevis, and best developed in H. pulchellus. In postmetamorphic animals, the olfactory epithelium (air-sensitive organ) was relatively bigger in terrestrial species (R. arenarum and H. pulchellus), whereas the vomeronasal and the middle chamber epithelia (water-sensitive organs) was best developed in X. laevis. A small olfactory recess (likely homologous with the middle chamber epithelium) was found in R. arenarum juveniles, but not in H. pulchellus. These results support the association of the vomeronasal and middle chamber epithelia with aquatic olfaction, as seen by their enhanced development in the secondarily aquatic juveniles of X. laevis. They also support a role for the larval buccal-exposed olfactory epithelium in assessment of oral contents: it was absent in X. laevis, an obligate suspension feeder, while present in the two grazing species. These initial quantitative results give, for the first time, insight into the functional importance of the peripheral olfactory subsystems across the anuran life cycle.

Transition and transfer from pediatric to adult care of the young adult with complex congenital heart disease.

This article focuses first on the process of transition and transfer of care of young adults with complex congenital heart disease. It defines the transition process and briefly discusses its history. It reviews the important aspects of transition, outlines the key elements of a successful transition program, and provides a curriculum appropriate for the young adult with congenital heart disease. Finally, it identifies the barriers to transfer of care, discusses the importance of a policy on timing, outlines the components of adult provider services that may be needed, and reviews the steps to an orderly transfer process.

Olfactory metamorphosis in the Coastal Giant Salamander (Dicamptodon tenebrosus).

This study examined the gross morphology and ultrastructure of the olfactory organ of larvae, neotenic adults, and terrestrial adults of the Coastal Giant Salamander (Dicamptodon tenebrosus). The olfactory organ of all aquatic animals (larvae and neotenes) is similar in structure, forming a tube extending from the external naris to the choana. A nonsensory vestibule leads into the main olfactory cavity. The epithelium of the main olfactory cavity is thrown into a series of transverse valleys and ridges, with at least six dorsal and nine ventral valleys lined with olfactory epithelium, and separated by ridges of respiratory epithelium. The ridges enlarge with growth, forming large flaps extending into the lumen in neotenes. The vomeronasal organ is a diverticulum off the ventrolateral side of the main olfactory cavity. In terrestrial animals, by contrast, the vestibule has been lost. The main olfactory cavity has become much broader and dorsoventrally compressed. The prominent transverse ridges are lost, although small diagonal ridges of respiratory epithelium are found in the lateral region of the ventral olfactory epithelium. The posterior and posteromedial wall of the main olfactory cavity is composed of respiratory epithelium, in contrast to the olfactory epithelium found here in aquatic forms. The vomeronasal organ remains similar to that in large larvae, but is now connected to the mouth by a groove that extends back through the choana onto the palate. Bowman's glands are present in the main olfactory cavity at all stages, but are most abundant and best developed in terrestrial adults. They are lacking in the lateral olfactory epithelium of the main olfactory cavity. At the ultrastructural level, in aquatic animals receptor cells of the main olfactory cavity can have cilia, short microvilli, a mix of the two, or long microvilli. Supporting cells are of two types: secretory supporting cells with small, electron-dense secretory granules, and ciliated supporting cells. Receptor cells of the vomeronasal organ are exclusively microvillar, but supporting cells are secretory or ciliated, as in the main olfactory cavity. After metamorphosis two distinct types of sensory epithelium occur in the main olfactory cavity. The predominant epithelium, covering most of the roof and the medial part of the floor, is characterized by supporting cells with large, electron-lucent vesicles. The epithelium on the lateral floor of the main olfactory cavity, by contrast, resembles that of aquatic animals. Both types have both microvillar and ciliated receptor cells. No important changes are noted in cell types of the vomeronasal organ after metamorphosis. A literature survey suggests that some features of the metamorphic changes described here are characteristic of all salamanders, while others appear unique to D. tenebrosus.

The market for new diabetes products and the role of third-party payors.

Diabetes devices and supplies ("Products") are paid for differently when used in different patient care settings, and when paid for by different third-party payors ("Payors"). Manufacturers of a Product need to understand the different markets defined by the Payors. Payors cover different population groups with different risks of experiencing diabetes. The Payors determine whether or not particular products will be made available to their eligible population. The Payors decide how much to pay for products that they decide to cover. Medicare is a good example of how product markets are determined by Payor decisions. Medicare makes national coverage decisions, binding across the United States, and permits local coverage decisions when there is no national decision. Manufacturers need to understand this process in order to determine whether to try to obtain national decisions or local decisions. Manufacturers also need to understand the payment methodologies used in different patient care settings in order to identify how they should market their Products in each of those settings.

How to get paid for a new diabetes product.

Manufacturers of diabetes devices and supplies ("Products") should consider developing information during the Products' clinical trials that will assist in the later marketing of their Products. Manufacturers should engage in the clinical trials of their Products physicians who may be able to provide future assistance in obtaining appropriate reimbursement codes for the Products. Manufacturers should develop during the clinical trial process cost-effectiveness information that can be used to pursue coverage and reimbursement decisions from third-party payors in the future. Different Product reimbursement codes are developed by the American Medical Association and by the Centers for Medicare and Medicaid Services. For both these organizations there is a long time frame to get any code established. Manufacturers can develop information in a way that will make these time periods shorter if the appropriate strategy is developed early in the Product development process.

Say goodbye and say hello: the transition from pediatric to adult gastroenterology.

Pediatric and adult gastroenterologists have identified an important issue to be addressed which entails the process of transition of care for youth affected by chronic gastrointestinal disorders. The adolescent years are a time of change and development, and may be significantly affected by conditions such as Crohn's disease or ulcerative colitis. Health care providers need to advocate and provide comprehensive, developmentally appropriate care for youth and families to facilitate the transition from the pediatric to the adult setting. The present article will review important aspects of the transition from the pediatric to the adult care health system.

The phylogeny of amphibian metamorphosis.

Frogs have one of the most extreme metamorphoses among vertebrates. How did this metamorphosis evolve? By combining the methods previously proposed by Mabee and Humphries (1993) and Velhagen (1997), I develop a phylogenetic method suited for rigorous analysis of this question. In a preliminary analysis using 12 transformation sequence characters and 36 associated event sequence characters, all drawn from the osteology of the skull, the evolution of metamorphosis is traced on an assumed phylogeny. This phylogeny has lissamphibians (frogs, salamanders, and caecilians) monophyletic, with frogs the sister group of salamanders. Successive outgroups used are temnospondyls and discosauriscids, both of which are fossil groups for which ontogenetic data are available. In the reconstruction of character evolution, an unambiguous change (synapomorphy) along the branch leading to lissamphibians is a delay in the lengthening of the maxilla until metamorphosis, in accordance with my previous suggestion (Reiss, 1996). However, widening of the interpterygoid vacuity does not appear as a synapomophy of lissamphibians, due to variation in the character states in the outgroups. From a more theoretical perspective, the reconstructed evolution of amphibian metamorphosis involves examples of heterochrony, through the shift of ancestral premetamorphic events to the metamorphic period, caenogenesis, through the origin of new larval features, and terminal addition, through the origin of new adult features. Other changes don't readily fit these categories. This preliminary study provides evidence that metamorphic changes in frogs arose as further modifications of changes unique to lissamphibians, as well as a new method by which such questions can be examined.

Teaching health care students about disability within a cultural competency context.

The training of health care providers has been identified as key to resolving the health disparities experienced by persons with disabilities. We contend that: 1) cultural competency provides a useful conceptual framework for teaching disability-related content to health professions students; 2) educational experiences can be structured to reflect the socio-cultural complexity of the 'disability culture;' 3) desired competencies associated with culture can be defined with regard to professionals' approach to patients with disabilities; 4) exposure to persons who have disabilities in their homes allows the student to make connections between the nuances of daily life with a disability and one's health care needs; 5) the framework allows the disability culture to be integrated with other cultural contexts, including race and ethnicity; and 6) the framework acknowledges the potential impact of providers' conscious or unconscious recognition of their potential membership in the disability culture on their approach to patients with disabilities.