Three‐drug combination antiretroviral therapy (ART) became available in 1996, dramatically improving the prognosis of people living with HIV. The clinical benefits of ART are due to the sustained ...viral load suppression and CD4 T cell gains. Major drawbacks of the first ART regimens were adverse events, and high pill burden, which led to the reduction of drug adherence resulting in frequent treatment discontinuations and the development of drug resistance. Due to increased viral potency of new antiretroviral drugs consideration of a two‐drug combination therapy repositioning occurred in an effort to reduce adverse events, drug‐drug interactions and cost, while maintaining a sustained antiviral effect. Various combinations of two‐drug regimens have been studied, and non‐inferiority compared to a three‐drug regimen has been shown only for some of them. In addition, a two‐drug combination regimen may not be suitable for every patient, especially those who are pregnant, those with tuberculosis or coexisting HBV infection. Furthermore no information has been generated concerning the secondary transmission of HIV from patients who have undetectable plasma viral load on two‐drug regimens. Additional studies of two‐drug combinations are also necessary to evaluate the debated existence of low viral replication in tissues and on immune activation. While there is no urgent need to routinely switch patients to two‐drug combination therapy, due to the availability of drug combinations without significant toxicities, dual regimens represent a suitable option that deserve long‐term evaluation before being introduced to clinical practice.
Stopping declines in biodiversity is critically important, but it is only a first step toward achieving more ambitious conservation goals. The absence of an objective and practical definition of ...species recovery that is applicable across taxonomic groups leads to inconsistent targets in recovery plans and frustrates reporting and maximization of conservation impact. We devised a framework for comprehensively assessing species recovery and conservation success. We propose a definition of a fully recovered species that emphasizes viability, ecological functionality, and representation; and use counterfactual approaches to quantify degree of recovery. This allowed us to calculate a set of 4 conservation metrics that demonstrate impacts of conservation efforts to date (conservation legacy); identify dependence of a species on conservation actions (conservation dependence); quantify expected gains resulting from conservation action in the medium term (conservation gain); and specify requirements to achieve maximum plausible recovery over the long term (recovery potential). These metrics can incentivize the establishment and achievement of ambitious conservation targets. We illustrate their use by applying the framework to a vertebrate, an invertebrate, and a woody and an herbaceous plant. Our approach is a preliminary framework for an International Union for Conservation of Nature (IUCN) Green List of Species, which was mandated by a resolution of IUCN members in 2012. Although there are several challenges in applying our proposed framework to a wide range of species, we believe its further development, implementation, and integration with the IUCN Red List of Threatened Species will help catalyze a positive and ambitious vision for conservation that will drive sustained conservation action. Detener la disminución de la biodiversidad es fundamental, pero es tan solo un primer paso para alcanzar metas de conservación más ambiciosas. La falta de un objetivo y una definición práctica de recuperación de las especies que sea aplicable en grupos taxonómicos causa que los objetivos de los planes de recuperación sean inconsistentes y frustra la posibilidad de informar y maximizar su impacto en la conservación. Hemos ideado un marco para evaluar exhaustivamente la recuperación de las especies y el éxito de conservación. Proponemos una definición de especies completamente recuperadas, el cual enfatiza la viabilidad, la funcionalidad ecológica y la representación y utiliza enfoques contrafactuales para calcular el grado de recuperación. Esto nos permite calcular un conjunto de 4 medidas de conservación que demuestran los impactos de los esfuerzos de conservad ón hasta la fecha (legado de conservación); identifica la dependencia de una especie a las acciones de conservación (dependencia de conservación); calcula las ganancias esperadas a mediano plazo de una acción de conservación (ganancia de conservación) y los requisitos específicos para alcanzar la máxima recuperación posible a largo plazo (potencial de recuperación). Estas medidas pueden incentivar el establecimiento y logro de objetivos ambiciosos de conservación. Ilustramos el uso del marco aplicándolo en un vertebrado, un invertebrado, una planta leñosa y una planta herbácea. Nuestro enfoque representa un marco preliminar para la creación de una Lista Verde Especies de la Unión Internacional para la Conservación de la Naturaleza (UICN), la cual fue ordenada por una resolución de los miembros de la mencionada institución en el 2012. A pesar de que existen varias dificultades para aplicar el marco propuesto en un grupo amplio de especies, creemos que continuar su desarrollo, implementación e integración con la Lista Roja de Especies Amenazadas de la UICN contribuirá a catalizar una visión positiva y ambiciosa de conservación que conducirá a una acción de conservación sostenida. 阻止生物多祥性的減少十分重要，但这仅仅是实现更远大保护目标的第一歩。由于对“物种恢复”的概念 缺少ー个客观实际、适用于各种类群生物的定义，致使恢复计划目标不一致，并且也阻碍了对保护影响力的报告 和最大化。因此，我们设计了一个综合评估物种恢复和保护成功的框架。我们提出了“完全恢复” 物种的定义， 这个定义强调物种的生存能力、生态功能和代表性，我们还运用反事实分析法来量化物种恢复的程度。我们可 以计算这样四个保护指标，包括分析至今为止保护行动的影响カ(保护遗产) 、确定物种对保护行动的依赖性 (保护依赖1É )、量化保护行动在中期的预期目标(保护成效) ，以及指明远期要实现最大可能恢复所需条件(恢 复潜力) 。这些指标可以刺激宏远保护目标的建立和实现。我们将此框架分別用于ー种脊椎动物、无脊椎动 物、木本植物和草本植物, 以说明这些指标的用法。我们提出的方法是〈く世界自然保护联盟物种绿色名录》的 ー个初步框架，这是由IUCN成员在2012年的ー项决议授权下进行的。虽然这个框架在不同物种中大范围的 应用还面临ー些挑战，但我们相信它在未来的发展、实施并与《IUCN受威胁物种红色名录》的整合，可以帮助 催生出ー个积极远大的保护蓝图，以驱动持续的保护行动。
Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent ...tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.
Species interactions matter to conservation. Setting an ambitious recovery target for a species requires considering the size, density, and demographic structure of its populations such that they ...fulfill the interactions, roles, and functions of the species in the ecosystems in which they are embedded. A recently proposed framework for an International Union for Conservation of Nature Green List of Species formalizes this requirement by defining a fully recovered species in terms of representation, viability, and functionality. Defining and quantifying ecological function from the viewpoint of species recovery is challenging in concept and application, but also an opportunity to insert ecological theory into conservation practice. We propose 2 complementary approaches to assessing a species’ ecological functions: confirmation (listing interactions of the species, identifying ecological processes and other species involved in these interactions, and quantifying the extent to which the species contributes to the identified ecological process) and elimination (inferring functionality by ruling out symptoms of reduced functionality, analogous to the red‐list approach that focuses on symptoms of reduced viability). Despite the challenges, incorporation of functionality into species recovery planning is possible in most cases and it is essential to a conservation vision that goes beyond preventing extinctions and aims to restore a species to levels beyond what is required for its viability. This vision focuses on conservation and recovery at the species level and sees species as embedded in ecosystems, influencing and being influenced by the processes in those ecosystems. Thus, it connects and integrates conservation at the species and ecosystem levels.
Evaluación de la Función Ecológica en el Contexto de Recuperación de Especies
Resumen
Las interacciones entre especies son de importancia para la conservación. La definición de una meta ambiciosa de recuperación para una especie requiere considerar el tamaño, la densidad y la estructura demográfica de sus poblaciones de tal manera que lleven a cabo las interacciones, papeles y funciones de las especies en los ecosistemas donde viven. Un marco de referencia propuesto recientemente para una Lista Verde de Especies de la Unión Internacional para la Conservación de la Naturaleza (UICN)formaliza este requerimiento mediante la definición de una especie completamente recuperada en términos de su representación, viabilidad y funcionalidad. La definición y cuantificación de la función ecológica desde la perspectiva de la recuperación de especies es un reto conceptual y de aplicación, pero también es un oportunidad para insertar la teoría ecológica en la práctica de la conservación. Proponemos 2 métodos complementarios para evaluar las funciones ecológicas de una especie: confirmación (listado de interacciones de la especie, identificación de procesos ecológicos y otras especies involucradas en estas interacciones) y eliminación (inferencia de la funcionalidad descartando los síntomas de reducción en la funcionalidad, análogo al método de la lista roja que enfoca los síntomas de reducción en la viabilidad). A pesar de los retos, la incorporación de la funcionalidad en la planificación de la recuperación de especies es posible en la mayoría de los casos y es esencial para una visión de la conservación que vaya más allá de la prevención de extinciones y que tenga como objetivo restaurar a una especie a niveles más allá de lo que se requiere para su viabilidad. Su visión se centra en la conservación y recuperación a nivel de especies y ve a las especies como componentes de los ecosistemas, influyendo y siendo influenciadas por los procesos en esos ecosistemas. Así, conecta e integra la conservación a nivel de especies y ecosistemas.
摘要
物种间的相互作用对保护至关重要。设定远大的物种恢复目标需要考虑其种群大小、密度和种群统计结构, 以确保物种能在其所处的生态系统中实现种间互作和物种自身的作用与功能。最近提出的《国际自然保护联盟 (IUCN) 绿色物种名录》框架正式纳入了这项需求, 提出从代表性、生存力和功能性三个方面来定义完全恢复的物种。从物种恢复的角度来定义和量化其生态功能, 在概念和应用上都具有挑战性, 但这也是在保护实践中引入生态学理论的重要机遇。我们提出了两种互补的方法来评估物种的生态功能: 一是直接确认, 即列出物种的互作、确定互作中涉及的生态学过程和其它物种, 并量化物种对该生态过程的贡献;二是消除法, 即通过排除功能性受损后的症状来推断功能, 这与红色名录中关注生存力降低后的症状的方法类似。虽然还存在上述挑战, 但在大多数情况下将功能性纳入物种恢复计划是可行的, 而且这对于不仅旨在防止灭绝、更要将物种恢复到生存所需水平的保护愿景来说至关重要。这一愿景强调物种水平的保护和恢复, 将物种视为生态系统的一部分, 影响着生态系统过程的同时也受其影响。因此, 它也连接和整合了物种及生态系统水平的保护。【翻译: 胡怡思; 审校: 聂永刚】
Article impact statement: The ecological functionality concept is applicable to species conservation and supports an ambitious definition of species recovery.
We created a database of lost and rediscovered tetrapod species, identified patterns in their distribution and factors influencing rediscovery. Tetrapod species are being lost at a faster rate than ...they are being rediscovered, due to slowing rates of rediscovery for amphibians, birds and mammals, and rapid rates of loss for reptiles. Finding lost species and preventing future losses should therefore be a conservation priority. By comparing the taxonomic and spatial distribution of lost and rediscovered tetrapod species, we have identified regions and taxa with many lost species in comparison to those that have been rediscovered—our results may help to prioritise search effort to find them. By identifying factors that influence rediscovery, we have improved our ability to broadly distinguish the types of species that are likely to be found from those that are not (because they are likely to be extinct). Some lost species, particularly those that are small and perceived to be uncharismatic, may have been neglected in terms of conservation effort, and other lost species may be hard to find due to their intrinsic characteristics and the characteristics of the environments they occupy (e.g. nocturnal species, fossorial species and species occupying habitats that are more difficult to survey such as wetlands). These lost species may genuinely await rediscovery. However, other lost species that possess characteristics associated with rediscovery (e.g. large species) and that are also associated with factors that negatively influence rediscovery (e.g. those occupying small islands) are more likely to be extinct. Our results may foster pragmatic search protocols that prioritise lost species likely to still exist.
Lost species tend to be highly threatened, but we cannot protect them effectively because we do not know where they are, or even if they still exist. This study reveals patterns in their distribution, and factors that influence their rediscovery—it will help to prioritise search effort to find them.
Thermoforming, a commonly used method to manufacture components from fibre reinforced thermoplastic laminates, involves heating the composite to its melt/softening temperature and then applying ...suitable forces to mould the composite to the required shape. Acquiring complex curvature shapes involves flow phenomena such as interply slip, intraply shear and squeeze flow. To date, the intraply shear mechanism is the least well understood. Approaches have been made to determine both longitudinal and transverse steady intraply shear viscosities of molten unidirectional continuous fibre-reinforced composites in the past but with conflicting results. No truly comprehensive characterisation has been carried out on these materials under a steady shear rate deformation mode. The present study concentrated on experimentally establishing the intraply shear behaviour of carbon fibre reinforced polyetheretherketone (APC-2). Two basic orientations were considered, one where the fibres in the lay-up were parallel to the pull-out direction and the other where the fibres were perpendicular to the pull-out direction. Values of longitudinal and transverse shear viscosities were determined for shear rates between 0.002 and 0.02
s
−1. The viscosity was highly shear-rate dependent, and was best modelled using a ‘power-law’. At a rate of 0.01
s
−1 the longitudinal viscosity was in the 1
MPa
s range, and approximately 2.5 times the transverse value. These values are several orders of magnitude greater than those determined using more traditional means, such as torsional rheometry, but agree with results obtained using a picture frame test method.
A survey of fecal samples found enterococcal excretion in 82% of 388 bank voles (Clethrionomys glareolus), 92% of 131 woodmice (Apodemus sylvaticus), and 75% of 165 badgers (Meles meles). ...Vancomycin-resistant enterococci, all Enterococcus faecium of vanA genotype, were excreted by 4.6% of the woodmice and 1.2% of the badgers, but by none of the bank voles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
The aim of the study was to evaluate the predictive value of clinical and molecular risk factors, including peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA) and ...mitochondrial RNA (mtRNA), for the development of lactic acidosis (LA) and symptomatic hyperlactataemia (SHL).
Methods
In a substudy of a large multicentre, randomized trial of three antiretroviral regimens, all containing didanosine (ddI) and stavudine (d4T), in antiretroviral‐naïve, HIV‐1‐infected patients, patients with LA/SHL (‘cases’) were compared with those without LA/SHL in a univariate analysis, with significant parameters analysed in a multivariate model. In a molecular substudy, PBMC mtDNA and mtRNA from cases and matched controls at baseline and time of event were examined.
Results
In 911 subjects followed for a median of 192 weeks, 24 cases were identified (14 SHL and 10 LA). In univariate analysis, cases were more likely to be female (P=0.05) and to have a high body mass index (BMI) (P=0.02). In multivariate analyses, only BMI remained an independent predictor of the development of LA/SHL (P=0.03). Between cases and controls there was no significant difference in mtDNA copy number at baseline (389 vs. 411 copies/cell, respectively; P=0.60) or at time of event (329 vs. 474 copies/cell, respectively; P=0.21), in the change in mtDNA copy number from baseline to event (−65 vs. +113 copies/cell, respectively; P=0.12), in mtRNA expression at baseline or time of event, or in the change in mtRNA expression from baseline to event.
Conclusion
The development of LA/SHL was associated with increased BMI, but PBMC mtDNA and mtRNA did not predict LA/SHL. This demonstrates the ineffectiveness of routine measurement of PBMC mtDNA in patients on ddI and d4T as a means of predicting development of LA/SHL.
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