Clinical trial update: National Cancer Institute of Canada

The Breast Cancer Site Group (BCSG) of the National Cancer Institute of Canada (NCIC) Clinical Trials Group (CTG) has conducted a wide variety of clinical trials focussing on large phase III trials of adjuvant chemotherapy, adjuvant hormonal therapy, and optimal delivery of adjuvant radiation therapy. The Group has also fostered, together with the NCIC CTG Investigational New Drug (IND) Program, a series of phase II and phase I/II studies which will be carried through if possible, into the phase III setting

Relationship between conservation biology and ecology shown through machine reading of 32,000 articles

Conservation biology was founded on the idea that efforts to save nature depend on a scientific understanding of how it works. It sought to apply ecological principles to conservation problems. We investigated whether the relationship between these fields has changed over time through machine reading the full texts of 32,000 research articles published in 16 ecology and conservation biology journals. We examined changes in research topics in both fields and how the fields have evolved from 2000 to 2014. As conservation biology matured, its focus shifted from ecology to social and political aspects of conservation. The 2 fields diverged and now occupy distinct niches in modern science. We hypothesize this pattern resulted from increasing recognition that social, economic, and political factors are critical for successful conservation and possibly from rising skepticism about the relevance of contemporary ecological theory to practical conservation

Recent unrest (2002–2015) imaged by space geodesy at the highest risk Chilean volcanoes: Villarrica, Llaima, and Calbuco (Southern Andes)

Villarrica, Llaima, and Calbuco volcanoes are the most active and dangerous volcanoes in the Southern Andes, and we use Interferometric Synthetic Aperture Radar (InSAR) observations from multiple satellites (ERS-2, ENVISAT, ALOS, RADARSAT-2, COSMO-SkyMed, TerraSAR-X, Sentinel-1A and ALOS-2) to constrain ground deformation that spans episodes of unrest and eruption at all three volcanoes between 2002 and 2015. We find episodes of ground deformation at each volcano, which we invert using analytic elastic half space models to make some of the first geophysical inferences about the source depths of potential magma chambers. At Llaima, we interpret that the VEI 2 April 3, 2009 eruption was preceded by 6–15 cm of precursory ground uplift one month before from a source 5 km below the surface on the western side of the edifice. The VEI 2 March 3, 2015 Villarrica eruption was followed by a short lived uplift of 5 cm in the SE part of the volcano from a source depth of 6 km. The VEI 4 April 22–23, 2015 Calbuco eruption produced 12 cm of coeruptive subsidence from a source depth 8–11 km and offset 2 km S from the summit. Importantly, we do not find clear evidence that the January 1, 2008, the March 3, 2015 and April 22, 2015 eruptions at Llaima, Villarrica and Calbuco volcanoes were preceded by either transient or continuous ground uplift. There are several possible explanations for the lack of precursory deformation at each volcano – it is possible that any precursory deformation occurred only hours before the eruption (e.g., at Calbuco), pre-eruptive inflation was canceled by co-eruptive subsidence (as we inferred happened during the April 2009 Llaima eruption), the pre-eruptive deformation was too small to be detectable in areas with persistent topography correlated phase delays, pressurized source are deep, or that open-vent volcanoes like Villarrica and Llaima do not pressurize. At all three volcanoes, X and C band interferograms decorrelate in a few weeks due to vegetation, snow and ice, and have persistent atmospheric phase delays that we find cannot be reliably removed with available global weather models. The low number of SAR acquisitions therefore makes it challenging to reliably measure unaliased deformation. We recommend a multi-satellite observing strategy with short repeat periods, frequently acquired high-resolution digital elevation models, and with acquisitions during every satellite overflight that may improve the temporal resolution of measurements

Recent unrest (2002–2015) imaged by space geodesy at the highest risk Chilean volcanoes: Villarrica, Llaima, and Calbuco (Southern Andes)

Villarrica, Llaima, and Calbuco volcanoes are the most active and dangerous volcanoes in the Southern Andes, and we use Interferometric Synthetic Aperture Radar (InSAR) observations from multiple satellites (ERS-2, ENVISAT, ALOS, RADARSAT-2, COSMO-SkyMed, TerraSAR-X, Sentinel-1A and ALOS-2) to constrain ground deformation that spans episodes of unrest and eruption at all three volcanoes between 2002 and 2015. We find episodes of ground deformation at each volcano, which we invert using analytic elastic half space models to make some of the first geophysical inferences about the source depths of potential magma chambers. At Llaima, we interpret that the VEI 2 April 3, 2009 eruption was preceded by 6–15 cm of precursory ground uplift one month before from a source 5 km below the surface on the western side of the edifice. The VEI 2 March 3, 2015 Villarrica eruption was followed by a short lived uplift of 5 cm in the SE part of the volcano from a source depth of 6 km. The VEI 4 April 22–23, 2015 Calbuco eruption produced 12 cm of coeruptive subsidence from a source depth 8–11 km and offset 2 km S from the summit. Importantly, we do not find clear evidence that the January 1, 2008, the March 3, 2015 and April 22, 2015 eruptions at Llaima, Villarrica and Calbuco volcanoes were preceded by either transient or continuous ground uplift. There are several possible explanations for the lack of precursory deformation at each volcano – it is possible that any precursory deformation occurred only hours before the eruption (e.g., at Calbuco), pre-eruptive inflation was canceled by co-eruptive subsidence (as we inferred happened during the April 2009 Llaima eruption), the pre-eruptive deformation was too small to be detectable in areas with persistent topography correlated phase delays, pressurized source are deep, or that open-vent volcanoes like Villarrica and Llaima do not pressurize. At all three volcanoes, X and C band interferograms decorrelate in a few weeks due to vegetation, snow and ice, and have persistent atmospheric phase delays that we find cannot be reliably removed with available global weather models. The low number of SAR acquisitions therefore makes it challenging to reliably measure unaliased deformation. We recommend a multi-satellite observing strategy with short repeat periods, frequently acquired high-resolution digital elevation models, and with acquisitions during every satellite overflight that may improve the temporal resolution of measurements

Synthesis of global satellite observations of magmatic and volcanic deformation: implications for volcano monitoring & the lateral extent of magmatic domains

Global Synthetic Aperture Radar (SAR) measurements made over the past decades provide insights into the lateral extent of magmatic domains, and capture volcanic process on scales useful for volcano monitoring. Satellite-based SAR imagery has great potential for monitoring topographic change, the distribution of eruptive products and surface displacements (InSAR) at subaerial volcanoes. However, there are challenges in applying it routinely, as would be required for the reliable operational assessment of hazard. The deformation detectable depends upon satellite repeat time and swath widths, relative to the spatial and temporal scales of volcanological processes. We describe the characteristics of InSAR-measured volcano deformation over the past two decades, highlighting both the technique’s capabilities and its limitations as a monitoring tool. To achieve this, we draw on two global datasets of volcano deformation: the Smithsonian Institution Volcanoes of the World database and the Centre for the Observation and Modelling of Earthquakes, Volcanoes and Tectonics volcano deformation catalogue, as well as compiling some measurement characteristics and interpretations from the primary literature. We find that a higher proportion of InSAR observations capture non-eruptive and non-magmatic processes than those from ground-based instrument networks, and that both transient ( 5 years) deformation episodes are under-represented. However, satellite radar is already used to assess the development of extended periods of unrest and long-lasting eruptions, and improved spatial resolution and coverage have resulted in the detection of previously unrecognised deformation at both ends of the spatial scale (~ 10 to > 1000 km²). ‘Baseline’ records of past InSAR measurements, including ‘null’ results, are fundamental for any future interpretation of interferograms in terms of hazard‚ both by providing information about past deformation at an individual volcano, and for assessing the characteristics of deformation that are likely to be detectable (and undetectable) using InSAR. More than half of all InSAR deformation signals attributed to magmatic processes have sources in the shallow crust (< 5 km depth). While the depth distribution of InSAR-derived deformation sources is affected by measurement limitations, their lateral distribution provides information about the extent of active magmatic domains. Deformation is common (24% of all potentially magmatic events) at loci ≥5 km away from the nearest active volcanic vent. This demonstrates that laterally extensive active magmatic domains are not exceptional, but can comprise the shallowest part of trans-crustal magmatic systems in a range of volcanic settings

Analysis of Population Structure: A Unifying Framework and Novel Methods Based on Sparse Factor Analysis

We consider the statistical analysis of population structure using genetic data. We show how the two most widely used approaches to modeling population structure, admixture-based models and principal components analysis (PCA), can be viewed within a single unifying framework of matrix factorization. Specifically, they can both be interpreted as approximating an observed genotype matrix by a product of two lower-rank matrices, but with different constraints or prior distributions on these lower-rank matrices. This opens the door to a large range of possible approaches to analyzing population structure, by considering other constraints or priors. In this paper, we introduce one such novel approach, based on sparse factor analysis (SFA). We investigate the effects of the different types of constraint in several real and simulated data sets. We find that SFA produces similar results to admixture-based models when the samples are descended from a few well-differentiated ancestral populations and can recapitulate the results of PCA when the population structure is more “continuous,” as in isolation-by-distance models

Synthesizing multi-sensor, multi-satellite, multi-decadal datasets for global volcano monitoring

Owing to practical limitations less than half of Earth's 1400 subaerial volcanoes have no ground monitoring and few are monitored consistently. Earth-observing satellite missions provide global and frequent measurements of volcanic activity that are closing these gaps in coverage. We compare databases of global, satellite-detections of ground deformation (1992–2016), SO₂ emissions (1978–2016), and thermal features (2000–2016) that together include 306 volcanoes. Each database has limitations in terms of spatial and temporal resolution but each technique contributed 45–86 unique detections of activity that were not detected by other techniques. Integration of these three databases shows that satellites detected ~10² volcanic activities per year before the year 2000 and ~103 activities per year after the year 2000. We find that most of the 54 erupting volcanoes without satellite-detections are associated with low volcano explosivity index eruptions and note that many of these eruptions (71%, 97/135) occurred in the earliest decades of remote sensing (pre-2000) when detection thresholds were high. From 1978 to 2016 we conduct a preliminary analysis of the timing between the onset of satellite-detections of deformation (N = 154 episodes, N = 71 volcanoes), thermal features (N = 16,544 episodes, N = 99 volcanoes), and SO₂ emissions (N = 1495 episodes, N = 116 volcanoes) to eruption start dates. We analyze these data in two ways: first, including all satellite-detected volcanic activities associated with an eruption; and second, by considering only the first satellite-detected activity related to eruption. In both scenarios, we find that deformation is dominantly pre-eruptive (47% and 57%) whereas available databases of thermal features and SO₂ emissions utilizing mainly low-resolution sensors are dominantly co-eruptive (88% and 76% for thermal features, 97% and 96% for SO₂ emissions)

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention

Background: A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders.&lt;p&gt;&lt;/p&gt; Aims: To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students.&lt;p&gt;&lt;/p&gt; Method: Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes.&lt;p&gt;&lt;/p&gt; Results: Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p&#60;.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating.&lt;p&gt;&lt;/p&gt; Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention

A mammalian functional-genetic approach to characterizing cancer therapeutics

Supplementary information is available online at http://www.nature.com/naturechemicalbiology/. Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/.Identifying mechanisms of drug action remains a fundamental impediment to the development and effective use of chemotherapeutics. Here we describe an RNA interference (RNAi)–based strategy to characterize small-molecule function in mammalian cells. By examining the response of cells expressing short hairpin RNAs (shRNAs) to a diverse selection of chemotherapeutics, we could generate a functional shRNA signature that was able to accurately group drugs into established biochemical modes of action. This, in turn, provided a diversely sampled reference set for high-resolution prediction of mechanisms of action for poorly characterized small molecules. We could further reduce the predictive shRNA target set to as few as eight genes and, by using a newly derived probability-based nearest-neighbors approach, could extend the predictive power of this shRNA set to characterize additional drug categories. Thus, a focused shRNA phenotypic signature can provide a highly sensitive and tractable approach for characterizing new anticancer drugs.National Institute of Mental Health (U.S.) (grant RO1 CA128803-03)American Association for Cancer ResearchMassachusetts Institute of Technology. Dept. of BiologyNational Cancer Institute (U.S.). Integrative Cancer Biology Program (grant 1-U54-CA112967

Patterns of polymorphism and linkage disequilibrium in cultivated barley

We carried out a genome-wide analysis of polymorphism (4,596 SNP loci across 190 elite cultivated accessions) chosen to represent the available genetic variation in current elite North West European and North American barley germplasm. Population sub-structure, patterns of diversity and linkage disequilibrium varied considerably across the seven barley chromosomes. Gene-rich and rarely recombining haplotype blocks that may represent up to 60% of the physical length of barley chromosomes extended across the ‘genetic centromeres’. By positioning 2,132 bi-parentally mapped SNP markers with minimum allele frequencies higher than 0.10 by association mapping, 87.3% were located to within 5 cM of their original genetic map position. We show that at this current marker density genetically diverse populations of relatively small size are sufficient to fine map simple traits, providing they are not strongly stratified within the sample, fall outside the genetic centromeres and population sub-structure is effectively controlled in the analysis. Our results have important implications for association mapping, positional cloning, physical mapping and practical plant breeding in barley and other major world cereals including wheat and rye that exhibit comparable genome and genetic features