Measuring the Influence of Side Effect Expectations, Beliefs, and Incident Side Effects on the Risk for Drug Discontinuation Among Individuals Starting New Medications, a Cross-sectional Study.

Purpose: To measure the impact of beliefs, expectations, side effects, and their combined effects on the risk for medication nonpersistence. Patients and methods: Using a cross-sectional design, individuals from Saskatchewan, Canada who started a new antihypertensive, cholesterol-lowering, or antihyperglycemic medication were surveyed about risk factors for nonpersistence including: (a) beliefs measured by a composite score of three questions asking about the threat of the condition, importance of the drug, and harm of the drug; (b) incident side effects attributed to treatment; and (c) expectations for side effects before starting treatment. Descriptive statistics and logistic regression models were used to quantify the influence of these risk factors on the outcome of nonpersistence. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results: Among 3,029 respondents, 5.8% (n=177) reported nonpersistence within four months after starting the new drug. After adjustment for numerous covariates representing sociodemographics, health-care providers, medication experiences and beliefs, both negative beliefs (OR: 7.26, 95%CI: 4.98-10.59) and incident side effects (OR: 8.00, 95%CI: 5.49-11.68) were associated with the highest odds of nonpersistence with no evidence of interaction. In contrast, expectations for side effects before starting treatment exhibited an important interaction with incident side effects following treatment initiation. Among respondents with incident side effects (n=741, 24.5%), the risk for early nonpersistence was 11.5% if they indicated an expectation for side effects before starting the medication compared to 23.6% if they did not (adjusted OR: 0.38, 95%CI: 0.25-0.60). Conclusion: Expectations for side effects may be a previously unrecognized but important marker of the probability to persist with treatment. A high percentage of new medication users appeared unprepared for the possibility of side effects from their new medication making them less resilient if side effects occur.

The only "lungless" frog has a glottis and lungs.

Blackburn et al. show using CT-scanning that the only previously reported "lungless" frog retains a glottis and lungs.

Increasing the impact of vertebrate scientific collections through 3D imaging: The openVertebrate (oVert) Thematic Collections Network.

The impact of preserved museum specimens is transforming and increasing by three-dimensional (3D) imaging that creates high-fidelity online digital specimens. Through examples from the openVertebrate (oVert) Thematic Collections Network, we describe how we created a digitization community dedicated to the shared vision of making 3D data of specimens available and the impact of these data on a broad audience of scientists, students, teachers, artists, and more. High-fidelity digital 3D models allow people from multiple communities to simultaneously access and use scientific specimens. Based on our multiyear, multi-institution project, we identify significant technological and social hurdles that remain for fully realizing the potential impact of digital 3D specimens.

Embryonic development of the neotropical pit viper Bothrops atrox (Serpentes: Viperidae: Crotalinae), with emphasis on pit organ morphogenesis and its evolution in snakes.

BACKGROUND: Bothrops atrox is a pit viper with a loreal pit organ, and its embryological development remains undescribed. Here, we provide a comprehensive description of the embryology of B. atrox, focusing on the loreal pit organ and cephalic scales. RESULTS: We characterized 13 developmental stages of B. atrox based on external features consistent with the embryogenesis of previously described snake species. The loreal pit organ originates from the circumorbital region and migrates to its final position. In Crotalinae, the pit organ first becomes visible at stage 28, whereas in Pythonidae labial, pit organs appear at Stage 35. Pit organs evolved independently three times in Serpentes, encompassing Boidae, Pythonidae, and Crotalinae. Boidae lacks embryological information for pit organs. Furthermore, we observed that head scalation onset occurs at Stage 33 in B. atrox, with fusion of scales surrounding the loreal pit organ. CONCLUSIONS: The embryology of pit organs in Pythonidae and Boidae species remains poorly understood. Our detailed embryological descriptions are critical for proposing developmental scenarios for pit organs and guiding future research on these structures.

Parental care contributes to vertical transmission of microbes in a skin-feeding and direct-developing caecilian.

BACKGROUND: Our current understanding of vertebrate skin and gut microbiomes, and their vertical transmission, remains incomplete as major lineages and varied forms of parental care remain unexplored. The diverse and elaborate forms of parental care exhibited by amphibians constitute an ideal system to study microbe transmission, yet investigations of vertical transmission among frogs and salamanders have been inconclusive. In this study, we assess bacteria transmission in Herpele squalostoma, an oviparous direct-developing caecilian in which females obligately attend juveniles that feed on their mother's skin (dermatophagy). RESULTS: We used 16S rRNA amplicon-sequencing of the skin and gut of wild caught H. squalostoma individuals (males, females, including those attending juveniles) as well as environmental samples. Sourcetracker analyses revealed that juveniles obtain an important portion of their skin and gut bacteria communities from their mother. The contribution of a mother's skin to the skin and gut of her respective juveniles was much larger than that of any other bacteria source. In contrast to males and females not attending juveniles, only the skins of juveniles and their mothers were colonized by bacteria taxa Verrucomicrobiaceae, Nocardioidaceae, and Erysipelotrichaceae. In addition to providing indirect evidence for microbiome transmission linked to parental care among amphibians, our study also points to noticeable differences between the skin and gut communities of H. squalostoma and that of many frogs and salamanders, which warrants further investigation. CONCLUSION: Our study is the first to find strong support for vertical bacteria transmission attributed to parental care in a direct-developing amphibian species. This suggests that obligate parental care may promote microbiome transmission in caecilians.

Redefining Possible: Combining Phylogenomic and Supersparse Data in Frogs.

The data available for reconstructing molecular phylogenies have become wildly disparate. Phylogenomic studies can generate data for thousands of genetic markers for dozens of species, but for hundreds of other taxa, data may be available from only a few genes. Can these two types of data be integrated to combine the advantages of both, addressing the relationships of hundreds of species with thousands of genes? Here, we show that this is possible, using data from frogs. We generated a phylogenomic data set for 138 ingroup species and 3,784 nuclear markers (ultraconserved elements [UCEs]), including new UCE data from 70 species. We also assembled a supermatrix data set, including data from 97% of frog genera (441 total), with 1-307 genes per taxon. We then produced a combined phylogenomic-supermatrix data set (a "gigamatrix") containing 441 ingroup taxa and 4,091 markers but with 86% missing data overall. Likelihood analysis of the gigamatrix yielded a generally well-supported tree among families, largely consistent with trees from the phylogenomic data alone. All terminal taxa were placed in the expected families, even though 42.5% of these taxa each had >99.5% missing data and 70.2% had >90% missing data. Our results show that missing data need not be an impediment to successfully combining very large phylogenomic and supermatrix data sets, and they open the door to new studies that simultaneously maximize sampling of genes and taxa.

The smallest of its kind: Description of a new cryptic Amnirana species (Amphibia, Anura, Ranidae) from West African rainforests.

The distribution of the White-Lipped Frog Amnirana albolabris was long assumed to extend from eastern-central to western African rainforests. However, recent molecular phylogenetic analyses revealed that this taxon likely represents several undescribed species. Because the name-bearing types were collected in Gabon, the distantly related West African populations clearly represent an undescribed species that partly occurs in sympatry with Amnirana fonensis. Based on an integrative taxonomic approach, including molecular, morphological, and acoustic data, we describe the 'albolabris' populations from the Upper Guinean Forest Zone as a new species, and redescribe the morphologically similar A. fonensis on the bases of a larger series of genotyped individuals, including the first known females. We also provide new biological information for A. fonensis, including their advertisement call, habitat, and reproductive data. The new species is sister to A. fonensis and the two species differ by 5.8% in the mitochondrial 16S ribosomal RNA gene. Morphologically, males of the new species are smaller and have relatively smaller humeral glands. Females of the new species seem to have shorter legs than A. fonensis. In comparison to A. fonensis, the advertisement call of the new species has a higher dominant frequency and more pronounced frequency modulation. The two species differ in their distribution and habitat preferences, as revealed by environmental niche modelling. Whereas the new species is restricted to the Upper Guinean forests and thus is a true lowland-rainforest inhabitant, A. fonensis lives predominantly in Guinean montane forests in the forest-savanna mosaic zone.

Physician influence on medication adherence, evidence from a population-based cohort.

BACKGROUND: The overall impact of physician prescribers on population-level adherence rates are unknown. We aimed to quantify the influence of general practitioner (GP) physician prescribers on the outcome of optimal statin medication adherence. METHODS: We conducted a retrospective cohort study using health administrative databases from Saskatchewan, Canada. Participants included physician prescribers and their patients beginning a new statin medication between January 1, 2012 and December 31, 2017. We grouped prescribers based on the prevalence of optimal adherence (i.e., proportion of days covered ≥ 80%) within their patient group. Also, we constructed multivariable logistic regression analyses on optimal statin adherence using two-level non-linear mixed-effects models containing patient and prescriber-level characteristics. An intraclass correlation coefficient was used to estimate the physician effect. RESULTS: We identified 1,562 GPs prescribing to 51,874 new statin users. The median percentage of optimal statin adherence across GPs was 52.4% (inter-quartile range: 35.7% to 65.5%). GP prescribers with the highest patient adherence (versus the lowest) had patients who were older (median age 61.0 vs 55.0, p<0.0001) and sicker (prior hospitalization 39.4% vs 16.4%, p<0.001). After accounting for patient-level factors, only 6.4% of the observed variance in optimal adherence between patients could be attributed to GP prescribers (p<0.001). The majority of GP prescriber influence (5.2% out of 6.4%) was attributed to the variance unexplained by patient and prescriber variables. INTERPRETATION: The overall impact of GP prescribers on statin adherence appears to be very limited. Even "high-performing" physicians face significant levels of sub-optimal adherence among their patients.

Diversity and function of the fused anuran radioulna.

In tetrapods, fusion between elements of the appendicular skeleton is thought to facilitate rapid movements during running, flying, and jumping. Although such fusion is widespread, frogs stand out because adults of all living species exhibit fusion of the zeugopod elements (radius and ulna, tibia and fibula), regardless of jumping ability or locomotor mode. To better understand what drives the maintenance of limb bone fusion in frogs, we use finite element modeling methods to assess the functional consequences of fusion in the anuran radioulna, the forearm bone of frogs that is important to both locomotion and mating behavior (amplexus). Using CT scans of museum specimens, measurement tools, and mesh-editing software, we evaluated how different degrees of fusion between the radius and ulna affect the von Mises stress and bending resistance of the radioulna in three loading scenarios: landing, amplexus, and long-axis loading conditions. We find that the semi-fused state observed in the radioulna exhibits less von Mises stress and more resistance to bending than unfused or completely fused models in all three scenarios. Our results suggest that radioulna morphology is optimized to minimize von Mises stress across different loading regimes while also minimizing volume. We contextualize our findings in an evaluation of the diversity of anuran radioulnae, which reveals unique, permanent pronation of the radioulna in frogs and substantial variation in wall thickness. This work provides new insight into the functional consequences of limb bone fusion in anuran evolution.

A new genus and species of frog from the Kem Kem (Morocco), the second neobatrachian from Cretaceous Africa.

Neobatrachia, a clade representing the majority of extant anuran diversity, is thought to have emerged and diversified during the Cretaceous. Most of the early diversification of neobatrachians occurred in southern Gondwana, especially the regions that are today South America and Africa. Whereas five extinct neobatrachians have been described from the Cretaceous of South America in the last decade, only one is known from Africa. This difference in the known extinct diversity is linked to the lack of well-preserved specimens, understudy of fragmentary remains, and lack of known Cretaceous sites in Africa. Study of fragmentary anuran remains from Africa could allow for the identification of previously unknown neobatrachians, allowing for a better understanding of their early diversification. We reanalysed several previously described anuran specimens from the well-known Kem Kem beds, including using CT-scanning. Through our osteological study, we determined that several cranial bones and vertebrae represent a new hyperossified taxon for which we provide a formal description. Comparison to other hyperossified anurans revealed similarities and affinity of this new taxon with the neobatrachians Beelzebufo (extinct) and Ceratophrys (extant). Phylogenetic analyses supported this affinity, placing the new taxon within Neobatrachia in an unresolved clade of Ceratophryidae. This taxon is the oldest neobatrachian from Africa, and reveals that neobatrachians were already widespread throughout southern Gondwana during the earliest Late Cretaceous.

Semicircular canal size constrains vestibular function in miniaturized frogs.

Miniaturization has evolved repeatedly in frogs in the moist leaf litter environments of rainforests worldwide. Miniaturized frogs are among the world's smallest vertebrates and exhibit an array of enigmatic features. One area where miniaturization has predictable consequences is the vestibular system, which acts as a gyroscope, providing sensory information about movement and orientation. We investigated the vestibular system of pumpkin toadlets, Brachycephalus (Anura: Brachycephalidae), a clade of miniaturized frogs from Brazil. The semicircular canals of miniaturized frogs are the smallest recorded for adult vertebrates, resulting in low sensitivity to angular acceleration due to insufficient displacement of endolymph. This translates into a lack of postural control during jumping in Brachycephalus and represents a physical constraint resulting from Poiseuille's law, which governs movement of fluids within tubes.

Bridging the Research Gap between Live Collections in Zoos and Preserved Collections in Natural History Museums.

Zoos and natural history museums are both collections-based institutions with important missions in biodiversity research and education. Animals in zoos are a repository and living record of the world's biodiversity, whereas natural history museums are a permanent historical record of snapshots of biodiversity in time. Surprisingly, despite significant overlap in institutional missions, formal partnerships between these institution types are infrequent. Life history information, pedigrees, and medical records maintained at zoos should be seen as complementary to historical records of morphology, genetics, and distribution kept at museums. Through examining both institution types, we synthesize the benefits and challenges of cross-institutional exchanges and propose actions to increase the dialog between zoos and museums. With a growing recognition of the importance of collections to the advancement of scientific research and discovery, a transformational impact could be made with long-term investments in connecting the institutions that are caretakers of living and preserved animals.

An integrated continuity of care measure improves performance in models predicting medication adherence using population-based administrative data.

OBJECTIVES: Continuity of care (COC) is considered an important determinant of medication adherence based on measures such as the usual provider continuity index (UPCI) that are derived exclusively from physician visit claims. This study aimed to: a) determine if high UPCI values predict physicians who deliver different clinical services; and b) compare UPCI with an integrated COC measure capturing physician visits, prescribing, and a complete medical examination in a multivariable model of patients receiving statin medications. METHODS: This was a retrospective cohort study of new statin users between 2012 and 2017 in Saskatchewan, Canada. We calculated sensitivity/specificity of a high UPCI value for predicting physicians who were prescribers of statins and/or providers of complete medical examinations. Next, we used logistic regression models to test two measures of COC (high UPCI value or an integrated COC measure) on the outcome of optimal statin adherence (proportion of days covered ≥80%). The DeLong test was used to compare predictive performance of the two models. RESULTS: Among 55,144 new statin users, a high UPCI was neither a sensitive or specific marker of physicians who prescribed statins or performed a complete medical examination. The integrated COC measure had a stronger association with optimal adherence [adjusted odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.50 to 1.63] than UPCI (adjusted OR = 1.23, 95% CI 1.19 to 1.28), and improved predictive performance of the adherence model. CONCLUSION: The number of physician visits alone appears to be insufficient to represent COC. An integrated measure improves predictive performance for optimal medication adherence in patients initiating statins.

Cost-related nonadherence can be explained by a general nonadherence framework.

BACKGROUND: A conceptual framework has been developed specifically for cost-related nonadherence (CRNA) that differs from models proposed for general medication nonadherence. OBJECTIVE: This study aimed to demonstrate that CRNA studies are best explained by a conceptual framework developed for general medication nonadherence. METHODS: A systematic literature review was conducted using MEDLINE via PubMed, CINAHL, ScienceDirect, and Google Scholar databases from 2008 to 2020. Articles were considered for inclusion if they were research studies, used a self-reported measure for CRNA, and provided self-reported data on factors associated with CRNA. RESULTS: A total of 58 studies were identified and included in the review. Factors related to financial pressures were consistently associated with CRNA corresponding to conceptual frameworks for both CRNA and general medication nonadherence. However, noneconomic factors, classified as moderators in the CRNA framework (i.e., patient factors, disease factors, clinician factors), consistently demonstrated independent effects, often with similar strength of association compared with economic factors. Overall, the pattern of risk factors identified in CRNA studies was consistent with general nonadherence except for indicators of poor health. Poor health was often associated with an increased risk of CRNA, whereas the inverse association is generally observed in general nonadherence studies (i.e., nonadherence higher in primary prevention vs. secondary prevention). However, the apparent disagreement was likely caused by the general population studied rather than a unique causal pathway for CRNA. CONCLUSION: Financial difficulties are extremely common among people who take prescription medications. However, current evidence is insufficient to support a conceptual framework that differs from general medication nonadherence.

Factors associated with early nonpersistence among patients experiencing side effects from a new medication.

BACKGROUND: Drug discontinuation (i.e., nonpersistence) is often attributed to the emergence of adverse effects. However, it is not known whether other factors increase the risk of nonpersistence when adverse effects occur. OBJECTIVES: To identify factors associated with early nonpersistence among patients experiencing adverse effects from newly prescribed medications. METHODS: A questionnaire was mailed to new users of antihypertensive, antihyperglycemic, and lipid-lowering medications in Saskatchewan, Canada, between 2019 and 2020. Only respondents experiencing adverse effects were included. Responses were compared between the nonpersistent group (i.e., people who had discontinued their medication) and the persistent group (i.e., those who were taking their medication at the time of the survey). Statistically significant factors were tested in multivariable logistic regression models. Odds ratios (ORs) and 95% CIs were reported. RESULTS: Of the 3973 returned questionnaires, 813 respondents experienced adverse -effects from their new medication and were included in the study. Of these, 143 respondents (17.5%) had stopped their medication at the time of survey completion; most discontinuations (72.1%) occurred within 1 month of the first dose. Nonpersistent patients were older, had lower income, and were less likely to be taking an antihyperglycemic medication. After covariate adjustment, 6 factors were independently associated with nonpersistence: age less than 65 years (OR 1.56 [95% CI 1.01-2.41]), female sex (1.67 [1.08-2.59]), health condition not considered dangerous (2.09 [1.25-3.51]), medication not considered important for health (6.90 [4.40-10.84]), failure to expect adverse effects before starting medication (2.67 [1.74-4.10]), and taking 2 or more medications (0.45 [0.27-0.73]). CONCLUSION: Despite the strong link between the emergence of adverse effects and early nonpersistence, our findings confirm that this association is highly influenced by several factors external to the physical experiences caused by the new medication.

The Impact of Age and Sex Concordance Between Patients and Physicians on Medication Adherence: A Population-Based Study.

PURPOSE: Age or sex concordance (same sex or same age range) may also be associated with medication adherence but was not fully investigated. We aim to quantify the impact of age and sex concordance on optimal adherence to statin medications. PATIENTS AND METHODS: A retrospective cohort study was conducted using population-based health administrative data from Saskatchewan, Canada. Participants were individuals newly initiated on statin medications between January 1, 2012, and December 31, 2017. The outcome was optimal adherence (proportion of days covered ≥ 80%) measured at one year after the first statin claim. The independent variables were sex and age concordance (age within five years) between patients and prescribers. The association between adherence outcome and sex/age concordance was analyzed by multivariable logistic regression models using generalized estimating equations controlled by a package of potential confounding factors. RESULTS: Among 51,874 new statin users, 20.6% (n = 10,710) were age concordant with prescriber. The vast majority of age concordance occurred in patients younger than 66 years (88.6%, 9,486/10,710). Sex concordance was observed in 62.8% (n = 32,551) of patients and age-sex combined concordance in 13.2% (n = 6,856). Among patients younger than 66 years (n = 36,641/51,874, 70.6%), age concordance did not have a significant impact on optimal adherence [adjusted OR (aOR) = 1.02, 95% CI 0.97 to 1.07]. Weak association between sex concordance (aOR = 1.05, 95% CI 1.00 to 1.11), and age-sex combined concordance (aOR = 1.05, 95% CI 0.99 to 1.12) was observed. CONCLUSION: Age and sex concordance were not statistically significant predictors of optimal statin adherence. However, a weak association was detected for sex concordance. Future studies should examine this factor in different health care settings.

Giant Tree Frog diversification in West and Central Africa: Isolation by physical barriers, climate, and reproductive traits.

Secondary sympatry amongst sister lineages is strongly associated with genetic and ecological divergence. This pattern suggests that for closely related species to coexist in secondary sympatry, they must accumulate differences in traits that mediate ecological and/or reproductive isolation. Here, we characterized inter- and intraspecific divergence in three giant tree frog species whose distributions stretch across West and Central Africa. Using genome-wide single-nucleotide polymorphism data, we demonstrated that species-level divergence coincides temporally and geographically with a period of large-scale forest fragmentation during the late Pliocene. Our environmental niche models further supported a dynamic history of climatic suitability and stability, and indicated that all three species occupy distinct environmental niches. We found modest morphological differentiation amongst the species with significant divergence in tympanum diameter and male advertisement call. In addition, we confirmed that two species occur in secondary sympatry in Central Africa but found no evidence of hybridization. These patterns support the hypothesis that cycles of genetic exchange and isolation across West and Central Africa have contributed to globally significant biodiversity. Furthermore, divergence in both ecology and reproductive traits appear to have played important roles in maintaining distinct lineages. At the intraspecific level, we found that climatic refugia, precipitation gradients, marine incursions, and potentially riverine barriers generated phylogeographic structure throughout the Pleistocene and into the Holocene. Further studies examining phenotypic divergence and secondary contact amongst these geographically structured populations may demonstrate how smaller scale and more recent biogeographic barriers contribute to regional diversification.

La sympatrie secondaire parmi les espèces sœurs est fortement associée à la divergence génétique et écologique. Ce modèle suggère que pour que des espèces étroitement liées coexistent en sympatrie secondaire, elles doivent accumuler des différences dans les traits qui contribuent à l'isolement écologique ou reproductif. Ici, nous avons caractérisé la divergence inter- et intra-spécifique chez trois espèces de grenouilles arboricoles géantes dont les distributions s'étendent à travers l'Afrique de l'Ouest et Centrale. Avec des données génétiques, nous avons démontré que la divergence au niveau des espèces coïncide temporellement et géographiquement avec une période de fragmentation forestière à la fin du Pliocène. Nos modèles de niches environnementales ont soutenu une histoire dynamique de stabilité climatique, et ont indiqué que les trois espèces occupent des niches environnementales distinctes. Nous avons trouvé une différenciation morphologique modeste parmi les trois espèces mais une divergence significative dans le diamètre du tympan et les cris des mâles. De plus, nous avons confirmé que deux espèces sont présentes en sympatrie secondaire en Afrique Centrale mais n'avons trouvé aucune preuve d'hybridation. Ces résultats soutiennent l'hypothèse que les cycles d'échange génétique et d'isolement à travers l'Afrique de l'Ouest et Centrale ont contribué à une profonde concentration de biodiversité dans la région. De plus, la divergence des traits écologiques et reproducteurs semble avoir joué un rôle important dans le maintien de lignées distinctes. Au niveau intra-spécifique, nous avons constaté que les refuges climatiques, les gradients de précipitation, les incursions marines et potentiellement les barrières fluviales ont généré une structure phylogéographique pendant le Pléistocène et jusqu'à l'Holocène. Des études examinant la divergence phénotypique et le contact secondaire entre ces populations géographiquement structurées pourraient démontrer comment des barrières biogéographiques à échelle plus petite et plus récentes contribuent à la diversification régionale.

Rapid phenotypic change in a polymorphic salamander over 43 years.

Color polymorphic animals offer a unique system for studying intraspecific phenotypic responses to climate change. Discrete color morphs are easy to identify, and correlated trait responses of morphs can indicate how climate warming may facilitate long-term maintenance of polymorphisms. We use a historical dataset spanning 43 years to examine temporal shifts in color morph frequency and body size in response to climate in the Eastern Red-backed Salamander, Plethodon cinereus, which contains a widespread striped/unstriped color polymorphism. We created a pipeline to extract high-throughput trait data from fluid-preserved museum specimens where we batch-photographed salamanders, de-aggregated individual specimens from photographs, and solicited help of community scientists to score color morphs. We used a linear modeling framework that includes information about spatial population structure to demonstrate that color morph frequency and body size vary in response to climate, elevation, and over time, with an overall trend of higher frequency and decreased body size of the striped morph, but increased size of the unstriped morph. These surprising results suggest that morphs may be responding to multiple climate and geographic drivers through co-adapted morphological changes. This work highlights new practices of extracting trait data from museum specimens to demonstrate species phenotypes response to climate change.

Re-evaluating the morphological evidence for the re-evolution of lost mandibular teeth in frogs.

Dollo's law of irreversibility states that once a complex structure is lost, it cannot be regained in the same form. Several putative exceptions to Dollo's law have been identified using phylogenetic comparative methods, but the anatomy and development of these traits are often poorly understood. Gastrotheca guentheri is renowned as the only frog with teeth on the lower jaw. Mandibular teeth were lost in the ancestor of frogs more than 200 million years ago and subsequently regained in G. guentheri. Little is known about the teeth in this species despite being a frequent example of trait "re-evolution," leaving open the possibility that it may have mandibular pseudoteeth. We assessed the dental anatomy of G. guentheri using micro-computed tomography and histology and confirmed the longstanding assumption that true mandibular teeth are present. Remarkably, the mandibular teeth of G. guentheri are nearly identical in gross morphology and development to upper jaw teeth in closely related species. The developmental genetics of tooth formation are unknown in this possibly extinct species. Our results suggest that an ancestral odontogenic pathway has been conserved but suppressed in the lower jaw since the origin of frogs, providing a possible mechanism underlying the re-evolution of lost mandibular teeth.

A Randomized Controlled Trial of a Pretransplant Educational Intervention in Kidney Patients.

Poor patient knowledge about transplantation is a significant problem following kidney transplant. A video-based educational intervention was developed to supplement standard education provided by transplant teams. METHODS: A multicenter randomized controlled trial tested the intervention delivered to patients undergoing assessment or waitlisted for kidney transplant. Adult participants were randomized to the control (standard education) or the intervention group, consisting of electronic access to the videos (or digital video disks if no internet) plus standard education. Differences between groups in changes in transplant knowledge (measured by the Kidney Transplant Understanding Tool), education satisfaction, self-efficacy, and quality of life (secondary outcomes) were evaluated by a preintervention and postintervention survey. Video viewing habits were tracked and described for patients in the intervention group. RESULTS: One hundred sixty-two patients were enrolled, with 132 completing both questionnaires (n = 64 intervention and n = 68 control), with similar enrollment from 3 Canadian sites. Video viewing statistics in the complete cases indicated that 78% (50/64) watched the videos, with 70% (45/64) viewing them electronically, while 8% (5/64) received digital video disks and self-reported participation. Baseline knowledge scores in the intent-to-treat population were 55.4 ± 6.5 and 55.7 ± 7.1 in the intervention and control, respectively. The mean knowledge change in the intervention (2.1 ± 3.6) was significantly higher than in the control group (0.8 ± 3.4, P < 0.02). In the per-protocol analysis (patients with objective evidence of watching at least 80% of the videos), the knowledge improvements were 3.4 ± 3.8. Video group participants reported higher satisfaction with education (P < 0.02) and expressed positive comments in open-ended feedback. CONCLUSIONS: Electronic video education in the pretransplant setting improved knowledge and satisfaction.