Las especies amenazadas son indicadoras de los puntos calientes de la regulación trófica en sentido descendente

Se ha considerado la introducción de mesopredadores y herbívoros extranjeros como el principal desencadenante de la extinción de mamíferos australianos. Estudios recientes sugieren que los efectos devastadores de las especies invasoras quedan mitigados por los superpredadores. Por lo tanto, la supervivencia de muchas especies amenazadas puede depender de la presencia y funcionalidad ecológica de los grandes predadores. El superpredador australiano, el dingo (Canis lupus dingo) ha sido muy perseguido por todo el continente, y es extremadamente raro encontrar poblaciones de dingos que no estén sujetas a un control letal. En este estudio pronosticamos que la presencia de especies amenazadas señala los lugares donde las poblaciones de dingos están relativamente intactas, y que su ausencia puede indicar que los dingos son raros o que sus poblaciones están socialmente fracturadas. La comparación entre un lugar que alberga a un marsupial amenazado, el kowari o rata marsupial de cola de pincel (Dasyuroides byrnei), y un lugar vecino, de donde falta el kowari, es concordante con el patrón que sugerimos. Palabras clave: Envenenamiento con 1080, Canis lupus dingo, Dasyuroides byrnei, Especie invasora, Control por predador, Superpredador.The introduction of alien mesopredators and herbivores has been implicated as the main driver of mammalian extinction in Australia. Recent studies suggest that the devastating effects of invasive species are mitigated by top–order predators. The survival of many threatened species may therefore depend on the presence and ecological functioning of large predators. Australia’s top predator, the dingo (Canis lupus dingo), has been intensively persecuted across the continent and it is extremely rare to find dingo populations that are not being subjected to lethal control. We predicted that the presence of threatened species point out places where dingo populations are relatively intact, and that their absence may indicate that dingoes are either rare or socially fractured. A comparison of a site which harbors a threatened marsupial, the kowari (Dasyuroides byrnei), and a neighboring site where the kowari is absent, offers support for this suggested pattern. Key words: 1080 poison–baiting, Canis lupus dingo, Dasyuroides byrnei, Invasive species, Predator control, Top predator.Se ha considerado la introducción de mesopredadores y herbívoros extranjeros como el principal desencadenante de la extinción de mamíferos australianos. Estudios recientes sugieren que los efectos devastadores de las especies invasoras quedan mitigados por los superpredadores. Por lo tanto, la supervivencia de muchas especies amenazadas puede depender de la presencia y funcionalidad ecológica de los grandes predadores. El superpredador australiano, el dingo (Canis lupus dingo) ha sido muy perseguido por todo el continente, y es extremadamente raro encontrar poblaciones de dingos que no estén sujetas a un control letal. En este estudio pronosticamos que la presencia de especies amenazadas señala los lugares donde las poblaciones de dingos están relativamente intactas, y que su ausencia puede indicar que los dingos son raros o que sus poblaciones están socialmente fracturadas. La comparación entre un lugar que alberga a un marsupial amenazado, el kowari o rata marsupial de cola de pincel (Dasyuroides byrnei), y un lugar vecino, de donde falta el kowari, es concordante con el patrón que sugerimos. Palabras clave: Envenenamiento con 1080, Canis lupus dingo, Dasyuroides byrnei, Especie invasora, Control por predador, Superpredador

Threatened species indicate hot-spots of top-down regulation

The introduction of alien mesopredators and herbivores has been implicated as the main driver of mammalian extinction in Australia. Recent studies suggest that the devastating effects of invasive species are mitigated by top-order predators. The survival of many threatened species may therefore depend on the presence and ecological functioning of large predators. Australia’s top predator, the dingo (Canis lupus dingo), has been intensively persecuted across the continent and it is extremely rare to find dingo populations that are not being subjected to lethal control. We predicted that the presence of threatened species point out places where dingo populations are relatively intact, and that their absence may indicate that dingoes are either rare or socially fractured. A comparison of a site which harbors a threatened marsupial, the kowari (Dasyuroides byrnei), and a neighboring site where the kowari is absent, offers support for this suggested pattern

Four-qubit entanglement from string theory

We invoke the black hole/qubit correspondence to derive the classification of four-qubit entanglement. The U-duality orbits resulting from timelike reduction of string theory from D=4 to D=3 yield 31 entanglement families, which reduce to nine up to permutation of the four qubits.Comment: 4 pages, 1 figure, 2 tables, revtex; minor corrections, references adde

The US Food and Drug Administration’s expedited approval programs: addressing premarket flexibility with enhanced postmarket evidence generation

When the editors of Clinical Trials solicited our review on the U.S. Food and Drug Administration’s (FDA) expedited development and review programs, we anticipated there would be accompanying commentaries from other academics with differing opinions, or perhaps from the perspectives of industry or venture capital. We hardly expected to initiate a discussion among the former Commissioner of the FDA, the current Director of the Center for Drug Evaluation and Research (CDER), and the Chief Medical Officer of the American Society of Clinical Oncology on the advantages and disadvantages to patients and clinicians of FDA’s expedited approval programs. But we appreciate the opportunity to have done so. To be clear, the goal of our review was to engage in constructive dialogue, discussing the implications of expedited approval programs on premarket and postmarket evidence generation, highlighting some specific concerns, and offering our recommendations for robust medical product evaluations that ensure high-quality clinical evidence is available to inform patient care and clinical decision-making. The FDA faces the challenging task of striking the right balance between ensuring that novel therapeutics are safe and effective and allowing promising new drugs to enter the market as quickly as possible. We agree with Dr. Califf that FDA’s regulatory approach should not ‘revert back to the strategy of the 1970s’.2 Likely in response to the desires frequently expressed by patients and clinicians, the U.S. Congress has enacted laws requiring the FDA to develop expedited development and review pathways to accelerate the availability of novel therapeutics. Some of these pathways necessarily offer potential flexibility with respect to the evidentiary standards that are required to demonstrate medical product safety and effectiveness and secure approval. Accordingly, we believe there is a need for corresponding efforts to strengthen the clinical evidence that is generated after market approval

The US Food and Drug Administration’s expedited approval programs: Evidentiary standards, regulatory trade-offs, and potential improvements

The United States Food and Drug Administration (FDA) has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of drugs approved by the FDA in recent years are associated with expedited programs. In this paper, we provide an overview of the evidentiary standards required by FDA’s expedited development and approval programs, summarize the findings of the recent academic literature demonstrating some of the limitations of these programs, and outline potential opportunities to address these limitations. Recent evidence suggests that therapeutic agents in the FDA’s expedited programs are approved on the basis of fewer and smaller studies that may lack comparator groups and random allocation, and rather than focusing on clinical outcomes for study endpoints, rely instead on surrogate markers of disease. Once on the market, agents receiving expedited approvals are often quickly incorporated into clinical practice and evidence generated in the postmarketing period may not necessarily address the evidentiary limitations at the time of market entry. Furthermore, not all pathways require additional postmarketing studies. Evidence suggests that drugs in expedited approval programs are associated with a greater likelihood that FDA will take a safety action following market entry. There are several opportunities to improve the timeliness, information value, and validity of the pre-and postapproval studies of drugs receiving expedited approvals. When use of nonrandomized and uncontrolled studies cannot be avoided prior to market entry, randomized trials should be mandatory in the postapproval period, unless there are strong justifications for not carrying out such studies. In the premarket period, validity of the surrogate markers can be improved by more rigorously evaluating their correlation with patient-relevant clinical outcomes. Opportunities to reduce the duration, complexity, and cost of postmarketing randomized trials should not compromise their validity and instead incorporate pragmatic ‘real-world’ design elements. Despite recent enthusiasm for widely using real world evidence, adaptive designs, and pragmatic trials in the regulatory setting, caution is warranted until large scale empirical evaluations demonstrate their validity compared to more traditional trial design

Introduced megafauna are rewilding the Anthropocene

© 2017 The Authors Large herbivorous mammals, already greatly reduced by the late-Pleistocene extinctions, continue to be threatened with decline. However, many herbivorous megafauna (body mass ≥ 100 kg) have populations outside their native ranges. We evaluate the distribution, diversity and threat status of introduced terrestrial megafauna worldwide and their contribution towards lost Pleistocene species richness. Of 76 megafauna species, 22 (∼29%) have introduced populations; of these eleven (50%) are threatened or extinct in their native ranges. Introductions have increased megafauna species richness by between 10% (Africa) and 100% (Australia). Furthermore, between 15% (Asia) and 67% (Australia) of extinct species richness, from the late Pleistocene to today, have been numerically replaced by introduced megafauna. Much remains unknown about the ecology of introduced herbivores, but evidence suggests that these populations are rewilding modern ecosystems. We propose that attitudes towards introduced megafauna should allow for broader research and management goals

Uniqueness of Bessel models: the archimedean case

In the archimedean case, we prove uniqueness of Bessel models for general linear groups, unitary groups and orthogonal groups.Comment: 22 page