What factors influence the rediscovery of lost tetrapod species?

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.

A quantitative global review of species population monitoring.

Species monitoring, defined here as the repeated, systematic collection of data to detect long-term changes in the populations of wild species, is a vital component of conservation practice and policy. We created a database of nearly 1200 schemes, ranging in start date from 1800 to 2018, to review spatial, temporal, taxonomic, and methodological patterns in global species monitoring. We identified monitoring schemes through standardized web searches, an online survey of stakeholders, in-depth national searches in a sample of countries, and a review of global biodiversity databases. We estimated the total global number of monitoring schemes operating at 3300-15,000. Since 2000, there has been a sharp increase in the number of new schemes being initiated in lower- and middle-income countries and in megadiverse countries, but a decrease in high-income countries. The total number of monitoring schemes in a country and its per capita gross domestic product were strongly, positively correlated. Schemes that were active in 2018 had been running for an average of 21 years in high-income countries, compared with 13 years in middle-income countries and 10 years in low-income countries. In high-income countries, over one-half of monitoring schemes received government funding, but this was less than one-quarter in low-income countries. Data collection was undertaken partly or wholly by volunteers in 37% of schemes, and such schemes covered significantly more sites and species than those undertaken by professionals alone. Birds were by far the most widely monitored taxonomic group, accounting for around half of all schemes, but this bias declined over time. Monitoring in most taxonomic groups remains sparse and uncoordinated, and most of the data generated are elusive and unlikely to feed into wider biodiversity conservation processes. These shortcomings could be addressed by, for example, creating an open global meta-database of biodiversity monitoring schemes and enhancing capacity for species monitoring in countries with high biodiversity. Article impact statement: Species population monitoring for conservation purposes remains strongly biased toward a few vertebrate taxa in wealthier countries.

Una Revisión Global Cuantitativa del Monitoreo Poblacional de Especies Resumen El monitoreo de especies, definido aquí como la recolección sistemática y repetida de datos para detectar cambios a largo plazo en las poblaciones de las especies silvestres, es un componente vital de la práctica y las políticas de la conservación. Generamos una base de datos de casi 1,200 esquemas, con un rango de fecha de inicio desde 1800 hasta 2018, para revisar los patrones espaciales, temporales, taxonómicos y metodológicos en el monitoreo global de especies. Identificamos los esquemas de monitoreo por medio de búsquedas estandarizadas en línea, una encuesta digital realizada a los actores, búsquedas a profundidad en una muestra de países y en una revisión global de las bases de datos sobre la biodiversidad. Estimamos el número total mundial de esquemas funcionales de monitoreo entre 3,300 y 15,000. Desde el 2000, ha habido un fuerte aumento en el número de esquemas nuevos que han iniciado en países de bajo o mediano ingreso y en países megadiversos, pero una disminución en los países de alto ingreso. El número total de esquemas de monitoreo en un país y su producto interno bruto per cápita tuvieron una correlación sólida y positiva. Los esquemas que estaban activos en 2018 lo habían estado en un promedio de 21 años en los países de alto ingreso, comparado con un promedio de 13 años en los países de mediano ingreso y de 10 años en los países de bajo ingreso. En los países de alto ingreso, más de la mitad de los esquemas de monitoreo recibieron financiamiento del gobierno, comparado con menos de un cuarto de los esquemas en los países de bajo ingreso. La recolección de datos se realizó parcial o totalmente por voluntarios en 37% de los esquemas, y dichos esquemas cubrieron significativamente más sitios y especies que aquellos realizados sólo por profesionales. Las aves fueron por mucho el grupo taxonómico más monitoreado, comprendiendo casi la mitad de todos los esquemas, pero este sesgo declinó con el tiempo. El monitoreo en la mayoría de los grupos taxonómicos todavía es disperso y descoordinado, y la mayoría de los datos generados son vagos y tienen poca probabilidad de alimentar procesos más amplios de conservación de biodiversidad. Estas deficiencias podrían abordarse, por ejemplo, creando una meta-base de datos globales abiertos de los esquemas de monitoreo de la biodiversidad y mejorando la capacidad para el monitoreo de especies en los países con alta biodiversidad.

Testing a global standard for quantifying species recovery and assessing conservation impact.

Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard.

RESUMEN: Reconociendo que era imperativo evaluar la recuperación de especies y el impacto de la conservación, la Unión Internacional para la Conservación de la Naturaleza (UICN) convocó en 2012 al desarrollo de una "Lista Verde de Especies" (ahora el Estatus Verde de las Especies de la UICN). Un marco de referencia preliminar de una Lista Verde de Especies para evaluar el progreso de las especies hacia la recuperación, publicado en 2018, proponía 2 componentes separados pero interconectados: un método estandarizado (i.e., medición en relación con puntos de referencia de la viabilidad de especies, funcionalidad y distribución antes del impacto) para determinar el estatus de recuperación actual (puntuación de recuperación de la especie) y la aplicación de ese método para estimar impactos en el pasado y potenciales de conservación basados en 4 medidas (legado de conservación, dependencia de conservación, ganancia de conservación y potencial de recuperación). Probamos el marco de referencia con 181 especies representantes de diversos taxa, historias de vida, biomas, y categorías (riesgo de extinción) en la Lista Roja de la IUCN. Con base en la distribución observada de la puntuación de recuperación de las especies, proponemos las siguientes categorías de recuperación de la especie: totalmente recuperada, ligeramente mermada, moderadamente mermada, mayormente mermada, gravemente mermada, extinta en estado silvestre, e inderterminada. Cincuenta y nueve por ciento de las especies se consideraron mayormente o gravemente mermada. Aunque hubo una relación negativa entre el riesgo de extinción y la puntuación de recuperación de la especie, la variación fue considerable. Algunas especies en las categorías de riesgo bajas fueron evaluadas como más lejos de recuperarse que aquellas con alto riesgo. Esto enfatiza que la recuperación de especies es diferente conceptualmente al riesgo de extinción y refuerza la utilidad del Estado Verde de las Especies de la UICN para comprender integralmente el estatus de conservación de especies. Aunque el riesgo de extinción no predijo el legado de conservación, la dependencia de conservación o la ganancia de conservación, se correlacionó positivamente con la potencial de recuperación. Solo 1.7% de las especies probadas fue categorizado como cero en los 4 indicadores de impacto de la conservación, lo que indica que la conservación ha jugado, o jugará, un papel en la mejoría o mantenimiento del estatus de la especie la gran mayoría de ellas. Con base en nuestros resultados, diseñamos una versión actualizada del marco de referencia para la evaluación que introduce la opción de utilizar una línea de base dinámica para evaluar los impactos futuros de la conservación en el corto plazo y redefine corto plazo como 10 años.

A strategy for the next decade to address data deficiency in neglected biodiversity.

Measuring progress toward international biodiversity targets requires robust information on the conservation status of species, which the International Union for Conservation of Nature (IUCN) Red List of Threatened Species provides. However, data and capacity are lacking for most hyperdiverse groups, such as invertebrates, plants, and fungi, particularly in megadiverse or high-endemism regions. Conservation policies and biodiversity strategies aimed at halting biodiversity loss by 2020 need to be adapted to tackle these information shortfalls after 2020. We devised an 8-point strategy to close existing data gaps by reviving explorative field research on the distribution, abundance, and ecology of species; linking taxonomic research more closely with conservation; improving global biodiversity databases by making the submission of spatially explicit data mandatory for scientific publications; developing a global spatial database on threats to biodiversity to facilitate IUCN Red List assessments; automating preassessments by integrating distribution data and spatial threat data; building capacity in taxonomy, ecology, and biodiversity monitoring in countries with high species richness or endemism; creating species monitoring programs for lesser-known taxa; and developing sufficient funding mechanisms to reduce reliance on voluntary efforts. Implementing these strategies in the post-2020 biodiversity framework will help to overcome the lack of capacity and data regarding the conservation status of biodiversity. This will require a collaborative effort among scientists, policy makers, and conservation practitioners.

Una Estrategia para la Siguiente Década para Enfrentar la Deficiencia de Datos de la Biodiversidad Ignorada Resumen La medida del avance hacia los objetivos internacionales para la biodiversidad requiere información sólida sobre el estado de conservación de las especies, la cual proporciona la Lista Roja de Especies Amenazadas de la Unión Internacional para la Conservación de la Naturaleza (UICN). Sin embargo, los grupos más hiperdiversos, como los invertebrados, las plantas y los hongos, carecen de datos y capacidad, particularmente en regiones megadiversas o de endemismo alto. Las políticas de conservación y las estrategias de biodiversidad dirigidas hacia el cese de la pérdida de biodiversidad para el 2020 necesitan ser adaptadas para solucionar estas insuficiencias de información para después del año 2020. Diseñamos una estrategia de ocho puntos para cerrar las brechas existentes en los datos mediante la reactivación de la investigación exploratoria en el campo sobre la distribución, abundancia y ecología de las especies; la vinculación más cercana entre la investigación taxonómica y la conservación; la mejora a las bases de datos mundiales sobre biodiversidad mediante la presentación obligatoria de datos espacialmente explícitos para las publicaciones científicas; el desarrollo de una base mundial de datos espaciales sobre las amenazas para la biodiversidad para facilitar las valoraciones de la Lista Roja de la UICN; la automatización de las preevaluaciones mediante la integración de datos de distribución y datos de amenazas espaciales; el desarrollo de la capacidad en la taxonomía, la ecología y el monitoreo de la biodiversidad en países con una gran riqueza de especies o endemismos; la creación de programas de monitoreo de especies para los taxones menos conocidos; el desarrollo de suficientes mecanismos de financiamiento para reducir la dependencia de los esfuerzos voluntarios. La implementación de estas estrategias en el marco de trabajo para la biodiversidad posterior al 2020 ayudará a superar la falta de capacidad y datos con respecto al estado de conservación de la biodiversidad. Lo anterior requerirá de un esfuerzo colaborativo entre científicos, formuladores de políticas y practicantes de la conservación.

An inventory of biodiversity data sources for conservation monitoring.

Many conservation managers, policy makers, businesses and local communities cannot access the biodiversity data they need for informed decision-making on natural resource management. A handful of databases are used to monitor indicators against global biodiversity goals but there is no openly available consolidated list of global data sets to help managers, especially those in high-biodiversity countries. We therefore conducted an inventory of global databases of potential use in monitoring biodiversity states, pressures and conservation responses at multiple levels. We uncovered 145 global data sources, as well as a selection of global data reports, links to which we will make available on an open-access website. We describe trends in data availability and actions needed to improve data sharing. If the conservation and science community made a greater effort to publicise data sources, and make the data openly and freely available for the people who most need it, we might be able to mainstream biodiversity data into decision-making and help stop biodiversity loss.

Assessing ecological function in the context of species recovery.

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.

Quantifying species recovery and conservation success to develop an IUCN Green List of Species.

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.

A comparative approach to assess drivers of success in mammalian conservation recovery programs.

The outcomes of species recovery programs have been mixed; high-profile population recoveries contrast with species-level extinctions. Each conservation intervention has its own challenges, but to inform more effective management it is imperative to assess whether correlates of wider recovery program success or failure can be identified. To contribute to evidence-based improvement of future conservation strategies, we conducted a global quantitative analysis of 48 mammalian recovery programs. We reviewed available scientific literature and conducted semistructured interviews with conservation professionals involved in different recovery programs to investigate ecological, management, and political factors associated with population recoveries or declines. Identifying and removing threats was significantly associated with increasing population trend and decreasing conservation dependence, emphasizing that populations are likely to continue to be compromised in the absence of effective threat mitigation and supporting the need for threat monitoring and adaptive management in response to new and potential threats. Lack of habitat and small population size were cited as limiting factors in 56% and 42% of recovery programs, respectively, and both were statistically associated with increased longer term dependence on conservation intervention, demonstrating the importance of increasing population numbers quickly and restoring and protecting habitat. Poor stakeholder coordination and management were also regularly cited by respondents as key weaknesses in recovery programs, indicating the importance of effective leadership and shared goals and management plans. Project outcomes were not influenced by biological or ecological variables such as body mass or habitat, which suggests that these insights into correlates of conservation success and failure are likely to be generalizable across mammals.

Sunitinib in combination with gemcitabine for advanced solid tumours: a phase I dose-finding study.

BACKGROUND: This phase I, dose-finding study determined the maximum tolerated dose (MTD), safety, and pharmacokinetics of sunitinib plus gemcitabine in patients with advanced solid tumours. METHODS: Two schedules with sunitinib (25-50 mg per day) and IV gemcitabine (750-1250 mg m(-2)) in escalating doses were studied. First, patients received sunitinib on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2) plus gemcitabine on days 1, 8, 22, and 29. Second, patients received sunitinib on a 2-weeks-on-1-week-off schedule (Schedule 2/1) plus gemcitabine on days 1 and 8. The primary endpoint was determination of MTD and tolerability. RESULTS: Forty-four patients received the combination (Schedule 4/2, n=8; Schedule 2/1, n=36). With no dose-limiting toxicities (DLTs) at maximum dose levels on Schedule 2/1, MTD was not reached. Grade 4 treatment-related AEs and laboratory abnormalities included cerebrovascular accident, hypertension, and pulmonary embolism (n=1 each), and neutropenia (n=3), thrombocytopenia and increased uric acid (both n=2), and lymphopenia (n=1). There were no clinically significant drug-drug interactions. Antitumor activity occurred across dose levels and tumour types. In poor-risk and/or high-grade renal cell carcinoma patients (n=12), 5 had partial responses and 7 stable disease ≥ 6 weeks. CONCLUSION: Sunitinib plus gemcitabine on Schedule 2/1 with growth factor support was well tolerated and safely administered at maximum doses of each drug, without significant drug-drug interactions.

An ex vivo culture model for orthodontically induced root resorption.

OBJECTIVES: Root resorption is a ubiquitous although undesirable sequela to orthodontic treatment. Current methods to investigate the pathophysiology have certain limitations. In pursuit to understand and develop treatment modalities for orthodontically induced root resorption, the ability to manipulate cells within their natural extracellular matrix in a three dimensional organotypic model is invaluable. The study aimed to develop a laboratory-based organotypic model to investigate the effect of orthodontic forces on the periodontium. METHODS: Mandibular slices of male Wistar rats were maintained in Trowel-typed cultures at 37°C in 5% carbon dioxide in air for 7 days with test specimens subjected to compressive forces at 50 g and 100g by stainless steel springs. Tissue architecture and cell viability were maintained under culture conditions. RESULTS: Osteoclast numbers increased significantly in both test groups whilst odontoclasts increased in the 50 g group. Immunohistochemistry demonstrated increased dentine sialoprotein expression in both test groups, suggesting changes in mineralization-related activity due to mechanical strain. CONCLUSION: The study showed initial cellular and molecular changes of key markers that relate to root resorption in response to mechanical loading. CLINICAL SIGNIFICANCE: Severe root resorption may occur when forces applied are heavy or transmitted over an extended period and could lead to mobility and tooth loss. This ex vivo model can be used to investigate cellular and molecular processes during orthodontic tooth movement which may advance the clinical management of root resorption.

Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure.

AIMS: To assess the antitumour activity, safety, pharmacokinetics and pharmacodynamics of continuous daily sunitinib dosing in patients with imatinib-resistant/intolerant gastrointestinal stromal tumour (GIST) and to assess morning dosing versus evening dosing. PATIENTS AND METHODS: In this open-label phase II study, patients were randomised to receive morning or evening dosing of sunitinib 37.5mg/day. The primary end-point was clinical benefit rate (CBR; percent complete responses+partial responses [PRs]+stable disease [SD] 24 weeks). Secondary end-points included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters and plasma biomarker levels. RESULTS: Sixty of 61 planned patients received treatment (30 per dosing group); 26 completed the study. Overall, the CBR was 53% (95% exact CI, 40-66): eight patients (13%) achieved objective PRs; 24 (40%) achieved SD 24 weeks. Median PFS was 34 weeks (95% CI, 24-49); median OS was 107 weeks (95% CI, 72 - not yet calculable). Most adverse events (AEs) were of grade 1 or 2 in severity, and were manageable through dose modification or standard interventions. No new AEs were apparent compared with the approved intermittent dosing schedule. Antitumour activity and safety were generally similar with morning and evening dosing. Continuous daily sunitinib dosing achieved and sustained effective drug concentrations without additional accumulation across cycles. Decreases from baseline in plasma levels of soluble KIT after 20 and 24 weeks of dosing correlated with longer OS. CONCLUSION: For patients with imatinib-resistant/intolerant GIST, continuous daily sunitinib dosing appears to be an active alternative dosing strategy with acceptable safety.

Development and genetic mapping of sequence-tagged microsatellites (STMs) in bread wheat (Triticum aestivum L.).

The density of SSRs on the published genetic map of bread wheat (Triticum aestivum L.) has steadily increased over the last few years. This has improved the efficiency of marker-assisted breeding and certain types of genetic research by providing more choice in the quality of SSRs and a greater chance of finding polymorphic markers in any cross for a chromosomal region of interest. Increased SSR density on the published wheat genetic map will further enhance breeding and research efforts. Here, sequence-tagged microsatellite profiling (STMP) is demonstrated as a rapid technique for the economical development of anonymous genomic SSRs to increase marker density on the wheat genetic map. A total of 684 polymorphic sequence-tagged microsatellites (STMs) were developed, and 380 were genetically mapped in three mapping populations, with 296 being mapped in the International Triticeae Mapping Initiative W7984 x Opata85 recombinant inbred cross. Across the three populations, a total of 479 STM loci were mapped. Several technological advantages of STMs over conventional SSRs were also observed. These include reduced marker deployment costs for fluorescent-based SSR analysis, and increased genotyping throughput by more efficient electrophoretic separation of STMs and a high amenability to multiplex PCR.

A wide-aperture dynamically focusing sagittal monochromator for X-ray spectroscopy and diffraction.

A scanning dynamically focusing sagittal X-ray monochromator accepting 7 mrad of the fan from a 6 T wiggler is in routine use on beamline 16.5 (ultra-dilute spectroscopy) of the SRS at CCLRC Daresbury Laboratory, UK. The energy range covered is 7-27 keV, with a horizontal spot size of <1.1 mm FWHM. Measured monochromatic flux from a Si 220 crystal pair is 1 x 10(11) photons s(-1) (100 mA)(-1) at 9 keV. This level of flux, usually associated with an insertion device on a third-generation source, permits collection of EXAFS data on concentrations at or below 10 ppm.

High levels of genetic diversity throughout the range of the Portuguese wheat landrace 'Barbela'.

BACKGROUND AND AIMS: Landrace populations represent an important intra-crop reservoir of biodiversity and source of novel gene alleles for use in breeding programmes. Here the aim was to measure the diversity of a wheat landrace, 'Barbela', from the north of Portugal. METHODS: DNA was extracted from 59 accessions of Barbela collected across its geographical range. Diversity was measured by microsatellite length polymorphisms using 27 primer pairs amplifying 34 polymorphic microsatellite loci. KEY RESULTS: High levels of polymorphism were found, with an average polymorphism information content of 0.52; an average of 4.77 alleles (range 2-11) were present at each locus, and half of these loci showed an additional allele in the reference variety 'Chinese Spring'. CONCLUSIONS: 'Barbela' is maintained from seeds collected by farmers, but it maintains high allelic variation, and no groupings of accessions were detected when analysed by geographical region, farm or climate, indicating that the wheat landrace is a homogeneous entity. The diversity within the farmer-maintained landrace demonstrates the importance of characterization and maintenance of landrace collections before valuable genetic combinations are lost as uniform commercial crops are introduced.

A new approach to extending the wheat marker pool by anchored PCR amplification of compound SSRs.

A study was undertaken to determine the utility in bread wheat of anchored PCR for the development of single locus SSR markers targeted at compound repeat motifs. In anchored PCR, microsatellite amplification is achieved using a single primer complementary to the flanking sequence, and one which anchors to the repeat junction of the compound SSR. The recovery rate of useable markers was found to be similar (43%) to that reported for conventionally generated SSRs. Thus, anchored PCR can be used to reduce the costs of marker development, since it requires that only half the number of primers be synthesised. Where fluorescence-based platforms are used, marker deployment costs are lower, since only the anchoring primers need to be labelled. In addition, anchored PCR improves the recovery of useful markers, as it allows assays to be generated from microsatellite clones with repeat sequences located close to their ends, a situation where conventional PCR amplification fails as two flanking primers cannot be designed. Strategies to permit the large-scale development of compound SSR markers amplified by anchored PCR are discussed.

A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).

BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.

Modelling femoral curvature in the sagittal plane: a cadaveric study.

This study examined the possibility of representing the mid third of the human femur with two straight sections. This portion of the femur visually has a distinct curvature, which can potentially present problems when considering implant stem designs to be introduced in this region. Sixteen femora were sectioned at 10 mm intervals along the femoral shaft in the mid third region (35-65 per cent of femoral length). Photographic records were obtained of each section against a consistent axis system to which all coordinates were referenced. The position of the centre of the medullary canal cross-sectional area along the femur, in relation to fixed orthogonal planes, has been analysed; the outer anterior cortex was also modelled. The results showed that the medullary centre of area plots and the anterior cortex coordinates are suitably modelled as two straight lines. For each bone it was possible to define the intersection point between the two straight sections (point of angulation), and the subtended angle between these sections (angle of incidence). The average point of angulation for the medullary plots occurred at 57 per cent along the femur, while the mean angle of incidence was 6.5 degrees. The anterior surface had an average point of angulation at 58 per cent along the femur with the mean angle of incidence being 22.2 degrees. The centre-line of the medulla was also found to be almost parallel to the outer anterior surface for sections distal to the point of angulation. It is proposed therefore, that this difference in angulation is the result of medullary expansion/cortical thinning towards the proximal extremity of the femur, causing the straight-line model of the medulla to angulate less than the outer anterior cortex.

Supervised teaching practice: a system for teacher support and quality assurance.

Supervised teaching practice is practical supervision of teaching under the tutelage of an established teacher. It is proposed as a cost-effective integrated approach to linking the support and development of teachers with quality assurance. In modern undergraduate medical curricula increasing value is placed on teaching and teacher-training. The response to the General Medical Council's demand for a new style of undergraduate medical education requires a system of practical and continuous training which will ensure the highest standard among teachers. Supervised teaching practice offers such a system.