Clinical Benefit and Revenues of Drugs Affected by Rare Pediatric Disease Priority Review Vouchers, 2017-2023.

OBJECTIVE: To determine the clinical benefit of drugs that earned or redeemed rare pediatric disease priority review vouchers (PRVs) from 2017 through 2023, and the revenues generated by such drugs. STUDY DESIGN: In this cohort study, Federal Register documents, publicly available health technology agency (HTA) assessments, and financial filings were used to identify drugs that were issued or redeemed using a rare pediatric disease PRV from 2017 through 2023, and to assess their added therapeutic benefit and drug-specific global revenues. RESULTS: Among the 36 drugs whose approval resulted in issuance of a rare pediatric PRV, therapeutic benefit ratings were available for 17 (47%), with 9 (53%) rated as high by at least 1 organization. Mean annual global revenues were $363 million (year 1), $621 million (year 2), and $850 million (year 3). The median annual list price for drugs issued a voucher was $788,705. Vouchers were then redeemed for 15 different drugs; out of 13 drugs with therapeutic benefit ratings, 4 (31%) were high value. CONCLUSIONS: Drugs that treat rare pediatric diseases generate similar revenues compared with other brand drugs, and drugs with high therapeutic benefit tend to generate more revenue than those with low therapeutic benefit. Drugs that earned the rare pediatric disease PRV for their manufacturer generate significant revenues and the voucher may not be necessary to incentivize drug development in the rare pediatric disease space.

Evaluating the reliability of DNA Barcoding for Central American Pacific shallow water echinoderms identification: a molecular taxonomy and database accuracy analysis / Evaluando la fiabilidad del Código de Barras de ADN para la identificación de equinodermos en aguas poco profundas del Pacífico de América Central: un análisis de taxonomía molecular y precisión de bases de datos

Abstract Introduction: Molecular divergence thresholds have been proposed to distinguish recently separated evolutive units, often displaying more accurate putative species assignments in taxonomic research compared to traditional morphological approaches. This makes DNA barcoding an attractive identification tool for a variety of marine invertebrates, especially for cryptic species complexes. Although GenBank and the Barcode of Life Data System (BOLD) are the major sequence repositories worldwide, very few have tested their performance in the identification of echinoderm sequences. Objective: We use COI echinoderm sequences from local samples and the molecular identification platforms from GenBank and BOLD, in order to test their accuracy and reliability in the DNA barcoding identification for Central American shallow water echinoderms, at genus and species level. Methods: We conducted sampling, tissue extraction, COI amplification, sequencing, and taxonomic identification for 475 specimens. The 348 obtained sequences were individually enquired with BLAST in GenBank as well as using the Identification System (IDS) in BOLD. Query sequences were classified depending on the best match result. McNemar's chi-squared, Kruskal-Wallis's and Mann-Whitney's U tests were performed to prove differences between the results from both databases. Additionally, we recorded an updated list of species reported for the shallow waters of the Central American Pacific. Results: We found 324 echinoderm species reported for Central American Pacific shallow waters. Only 118 and 110 were present in GenBank and BOLD databases respectively. We proposed 325 solved morphology-based identities and 21 provisional identifications in 50 putative taxa. GenBank retrieved 348 molecular-based identifications in 58 species, including twelve provisional identifications in tree taxa. BOLD recovered 170 COI identifications in 23 species with one provisional identification. Nevertheless, 178 sequences retrieved unmatched terms (in 34 morphology-based taxa). Only 86 sequences (25 %) were retrieved as correct identifications and 128 (37 %) as identification errors in both platforms. We include 84 sequences for eleven species not represented in GenBank and 65 sequences for ten species in BOLD Echinoderm COI databases. The identification accuracy using BLAST (175 correct and 152 incorrect identifications) was greater than with IDS engine (110 correct and 218 identification errors), therefore GenBank outperforms BOLD (Kruskal-Wallis = 41.625, df = 1, p < 0.001). Conclusions: Additional echinoderm sample references are needed to improve the utility of the evaluated DNA barcoding identification tools. Identification discordances in both databases may obey specific parameters used in each search algorithm engine and the available sequences. We recommend the use of barcoding as a complementary identification source for Central American Pacific shallow water echinoderm species.

Resumen Introducción: Se han propuesto los umbrales de divergencia molecular para distinguir unidades evolutivas recientemente separadas, que a menudo muestran asignaciones de especies putativas más precisas en la investigación taxonómica en comparación con los enfoques morfológicos tradicionales. Esto hace que los Códigos de Barras de ADN sean una herramienta de identificación atractiva para una variedad de invertebrados marinos, especialmente para complejos de especies crípticas. Aunque GenBank y Barcode of Life Data System (BOLD) son los principales repositorios de secuencias en todo el mundo, muy pocos han probado su desempeño en la identificación de secuencias de equinodermos. Objetivo: Utilizamos secuencias de equinodermos COI de muestras locales y las plataformas de identificación molecular de GenBank y BOLD, para probar su precisión y confiabilidad en la implementación de códigos de barras de ADN para equinodermos de aguas someras de Centroamérica, a nivel de género y especie. Métodos: Realizamos muestreo, extracción de tejido, amplificación de COI, secuenciación e identificación taxonómica de 475 especímenes. Las 348 secuencias obtenidas fueron consultadas individualmente con BLAST en GenBank así como utilizando el Sistema de Identificación (IDS) en BOLD. Las secuencias consultadas se clasificaron según el mejor resultado de coincidencia. Se realizaron las pruebas chi-cuadrado de McNemar, Kruskal-Wallis y U de Mann-Whitney para comprobar diferencias entre los resultados de ambas bases de datos. Además, registramos una lista actualizada de especies reportadas para las aguas someras del Pacífico Centroamericano. Resultados: Encontramos 324 especies de equinodermos reportadas para aguas someras (< 200 m) del Pacífico centroamericano. Sólo 118 y 110 estaban presentes en las bases de datos GenBank y BOLD respectivamente. Propusimos 325 identidades resueltas basadas en morfología y 21 identificaciones provisionales en 50 taxones putativos. GenBank recuperó 348 identificaciones de base molecular en 58 especies, incluidas doce identificaciones provisionales en tres taxones. BOLD recuperó 170 identificaciones de COI en 23 especies con una identificación provisional. Sin embargo, 178 secuencias recuperaron términos no coincidentes (en 34 taxones basados en morfología). Sólo 86 secuencias (25 %) se recuperaron como identificaciones correctas y 128 (37 %) como errores de identificación en ambas plataformas. Incluimos 84 secuencias para once especies no representadas en GenBank y 65 secuencias para diez especies ausentes en las bases de datos BOLD Echinoderm COI. La precisión de la identificación usando BLAST (175 identificaciones correctas y 152 incorrectas) fue mayor que con el motor IDS (110 correctas y 218 errores de identificación), por lo tanto, GenBank supera a BOLD (Kruskal-Wallis = 41.625, df = 1, p < 0.001). Conclusiones: Se necesitan muestras adicionales de equinodermos de referencia para mejorar la utilidad de las herramientas de identificación de códigos de barras de ADN evaluadas. Las discordancias de identificación en ambas bases de datos pueden obedecer a parámetros específicos utilizados en cada algoritmo de búsqueda y a las secuencias disponibles. Recomendamos el uso de códigos de barras como fuente de identificación complementaria para las especies de equinodermos de aguas someras del Pacífico centroamericano.

From species descriptions to diversity patterns: the validation of taxonomic data as a keystone for ant diversity studies reproducibility and accuracy.

Research findings in natural sciences need to be comparable and reproducible to effectively improve our understanding of ecological and behavioural patterns. In this sense, knowledge frontiers in biodiversity studies are directly tied to taxonomic research, especially in species-rich tropical regions. Here we analysed the taxonomic information available in 470 studies on Brazilian ant diversity published in the last 50 years. We aimed to quantify the proportion of studies that provide enough data to validate taxonomic identification, explore the frequency of studies that properly acknowledge their taxonomic background, and investigate the primary resources for ant identification in Brazil. We found that most studies on Brazilian ant diversity (73.6%) explicitly stated the methods used to identify their specimens. However, the proportion of papers that provide complete data for the repository institutions and vouchered specimens is vanishingly small (5.8%). Additionally, only 40.0% of the studies consistently presented taxon authorities and years of description, rarely referencing taxonomic publications correctly. In turn, the number of specialists and institutions consulted for ant identification in Brazil has increased in the last years, along with the number of studies that explicitly provide their taxonomic procedures for ant identification. Our findings highlight a shift between generations regarding the recognition of taxonomy as fundamental science, deepening our understanding of biodiversity.

An update to the inventory of shore-fishes from the Parque Nacional Sistema Arrecifal Veracruzano, Veracruz, México.

Data on marine and brackish-water fishes recorded in the area of the Parque Nacional Sistema Arrecifal Veracruzano in the southwest Gulf of Mexico were extracted from online aggregators of georeferenced location records, the recent ichthyological literature reviewed, and collections and observations made to provide a more complete faunal inventory for that park. Those actions added 95 species to a comprehensive inventory published in 2013, and brought the total to 472 species, an increase of 22%. Seventy-four percent of the additions came from online aggregators of georeferenced species records, which clearly demonstrates the value of reviewing and incorporating such data into species inventories. However, different aggregators recorded different sets of species, and some of their data were linked to outdated taxonomy or included identification errors. Hence individual records from multiple aggregators need to be obtained and reviewed for such issues when using such data to compile and revise faunal inventories. Existing lists also need to be carefully reviewed to ensure that errors are not perpetuated during updates.

Error cascade in taxonomy: The case of Cardiomya perrostrata (Mollusca: Bivalvia: Cuspidariidae) in Brazilian waters.

Successions of erroneous taxonomic identifications in biodiversity studies are an undesirable but not rare phenomenon. Such cascades of errors frequently involve taxa with few, polymorphic diagnostic characters, such as representatives of the cuspidariid genus Cardiomya. Four species of the genus are believed to live in Brazilian waters: C. cleryana (d'Orbigny, 1842), C. ornatissima (d'Orbigny, 1853), C. striata (Jeffreys, 1876) and C. perrostrata (Dall, 1881). Many reported occurrences of these species are based on misidentifications, but the error cascade of incorrect records of C. perrostrata is by far the most extensive. Although the species has been reported to live in Brazilian waters for about half a century, all previous records seem to be based on a succession of mistaken identifications. This paper redescribes C. perrostrata based on an analysis of the type series, several lots of museum vouchers and new material collected in the Campos Basis (Rio de Janeiro, Brazil). Ontogenetic changes in shell outline and ultrastructural details of the hinge plate, periostracal surface and larval shell are described and illustrated for the first time. Based on a critical appraisal of the literature, we present an updated geographic and bathymetric distribution of the species. Cardiomya perrostrata displays a gradual increase in the relative length of the rostrum during its ontogeny and in larger specimens the rostrum is more prominently curved upwards. The larval shell is of type 2D, measuring about 215-235 µm in length. The periostracum is minutely pitted and a lithodesma is present. Its distribution is Western Atlantic, ranging from 42°N to 30°S, in depths of 18 to 1646-1829 m. Cardiomya knudseni (Allen & Morgan, 1981), a possibly related amphi-Atlantic species whose type material has been lost, is regarded herein as a nomen dubium.

Impact of two policy interventions on dietary diversity in Ecuador.

OBJECTIVE: To differentiate the effects of food vouchers and training in health and nutrition on consumption and dietary diversity in Ecuador by using an experimental design. DESIGN: Interventions involved enrolling three groups of approximately 200 randomly selected households per group in three provinces in Ecuador. Power estimates and sample size were computed using the Optimal Design software, with a power of 80 %, at 5 % of significance and with a minimum detectable effect of 0·25 (sd). The first group was assigned to receive a monthly food voucher of $US 40. The second group was assigned to receive the same $US 40 voucher, plus training on health and nutrition issues. The third group served as the control. Weekly household values of food consumption were converted into energy intake per person per day. A simple proxy indicator was constructed for dietary diversity, based on the Food Consumption Score. Finally, an econometric model with three specifications was used for analysing the differential effect of the interventions. SETTING: Three provinces in Ecuador, two from the Sierra region (Carchi and Chimborazo) and one from the Coastal region (Santa Elena). SUBJECTS: Members of 773 households randomly selected (n 4343). RESULTS: No significant impact on consumption for any of the interventions was found. However, there was evidence that voucher systems had a positive impact on dietary diversity. No differentiated effects were found for the training intervention. CONCLUSIONS: The most cost-effective intervention to improve dietary diversity in Ecuador is the use of vouchers to support family choice in food options.

Short-run effects of accountability pressures on teacher policies and practices in the voucher system in Santiago, Chile.

This research analyzes the impact of the Adjusted Voucher Laws school rankings on low-performing schools in Santiago, Chile, and provides evidence on the effects of the pressures of accountability systems on teacher policies and practices. The empirical strategy is based on the fact that schools are ranked according to their position on a set of thresholds. We used a generalization of the traditional regression discontinuity design for the case where treatment assignment is determined by n variables. To gather information on teacher policies and practices, we conducted a survey of 4th-grade teachers in the Greater Santiago area. The results indicate that low-performing schools responded to the treatment by implementing policies that seek to improve their results in the short term. We also found no significant effects on teaching practices, suggesting that many of these changes are implemented top down from the school administrators, without involving teachers in the process.