Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment

Surveillance and Control Measures during Smallpox Outbreaks

Targeted surveillance and containment interventions have been successful for outbreak control and should be explored as alternatives to mass vaccination

The spectra and energies of classical double radio lobes

We compare two temporal properties of classical double radio sources: i) radiative lifetimes of synchrotron-emitting particles and ii) dynamical source ages. We discuss how these can be quite discrepant from one another, rendering use of the traditional spectral ageing method inappropriate: we contend that spectral ages give meaningful estimates of dynamical ages only when these ages are << 10^7 years. In juxtaposing the fleeting radiative lifetimes with source ages which are significantly longer, a refinement of the paradigm for radio source evolution is required. The changing spectra along lobes are explained, not predominantly by synchrotron ageing but, by gentle gradients in a magnetic field mediated by a low-gamma matrix which illuminates an energy-distribution of particles, controlled largely by classical synchrotron loss in the high magnetic field of the hotspot. The energy in the particles is an order of magnitude higher than that inferred from the minimum-energy estimate, implying that the jet-power is of the same order as the accretion luminosity produced by the quasar central engine. This refined paradigm points to a resolution of the findings of Rudnick et al (1994) and Katz-Stone & Rudnick (1994) that both the Jaffe-Perola and Kardashev-Pacholczyk model spectra are invariably poor descriptions of the curved spectral shape of lobe emission, and indeed that for Cygnus A all regions of the lobes are characterised by a `universal spectrum'. [abridged]Comment: LaTeX, 4 figures. To appear in A

What Drives Reproductive Maturity and Efficiency in Serotinous Boreal Conifers?

In boreal North America, much of the landscape is covered by fire-adapted forests dominated by serotinous conifers. For these forests, reductions in fire return interval could limit reproductive success, owing to insufficient time for stands to reach reproductive maturity i.e., to initiate cone production. Improved understanding of the drivers of reproductive maturity can provide important information about the capacity of these forests to self-replace following fire. Here, we assessed the drivers of reproductive maturity in two dominant and widespread conifers, semi-serotinous black spruce and serotinous jack pine. Presence or absence of female cones were recorded in approximately 15,000 individuals within old and recently burned stands in two distinct ecozones of the Northwest Territories (NWT), Canada. Our results show that reproductive maturity was triggered by a minimum tree size threshold rather than an age threshold, with trees reaching reproductive maturity at smaller sizes where environmental conditions were more stressful. The number of reproductive trees per plot increased with stem density, basal area, and at higher latitudes (colder locations). The harsh climatic conditions present at these higher latitudes, however, limited the recruitment of jack pine at the treeline ecotone. The number of reproductive black spruce trees increased with deeper soils, whereas the number of reproductive jack pine trees increased where soils were shallower. We examined the reproductive efficiency i.e., the number of seedlings recruited per reproductive tree, linking pre-fire reproductive maturity of recently burned stands and post-fire seedling recruitment (recorded up to 4 years after the fires) and found that a reproductive jack pine can recruit on average three times more seedlings than a reproductive black spruce. We suggest that the higher reproductive efficiency of jack pine can explain the greater resilience of this species to wildfire compared with black spruce. Overall, these results help link life history characteristics, such as reproductive maturity, to variation in post-fire recruitment of dominant serotinous conifers

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

Evolution of chloroplast retrograde signaling facilitates green plant adaptation to land

Chloroplast retrograde signaling networks are vital for chloroplast biogenesis, operation, and signaling, including excess light and drought stress signaling. To date, retrograde signaling has been considered in the context of land plant adaptation, but not regarding the origin and evolution of signaling cascades linking chloroplast function to stomatal regulation. We show that key elements of the chloroplast retrograde signaling process, the nucleotide phosphatase (SAL1) and 3'-phosphoadenosine-5'-phosphate (PAP) metabolism, evolved in streptophyte algae-the algal ancestors of land plants. We discover an early evolution of SAL1-PAP chloroplast retrograde signaling in stomatal regulation based on conserved gene and protein structure, function, and enzyme activity and transit peptides of SAL1s in species including flowering plants, the fern Ceratopteris richardii, and the moss Physcomitrella patens Moreover, we demonstrate that PAP regulates stomatal closure via secondary messengers and ion transport in guard cells of these diverse lineages. The origin of stomata facilitated gas exchange in the earliest land plants. Our findings suggest that the conquest of land by plants was enabled by rapid response to drought stress through the deployment of an ancestral SAL1-PAP signaling pathway, intersecting with the core abscisic acid signaling in stomatal guard cells

A physical map for the Amborella trichopoda genome sheds light on the evolution of angiosperm genome structure

Background: Recent phylogenetic analyses have identified Amborella trichopoda, an understory tree species endemic to the forests of New Caledonia, as sister to a clade including all other known flowering plant species. The Amborella genome is a unique reference for understanding the evolution of angiosperm genomes because it can serve as an outgroup to root comparative analyses. A physical map, BAC end sequences and sample shotgun sequences provide a first view of the 870 Mbp Amborella genome.Results: Analysis of Amborella BAC ends sequenced from each contig suggests that the density of long terminal repeat retrotransposons is negatively correlated with that of protein coding genes. Syntenic, presumably ancestral, gene blocks were identified in comparisons of the Amborella BAC contigs and the sequenced Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera and Oryza sativa genomes. Parsimony mapping of the loss of synteny corroborates previous analyses suggesting that the rate of structural change has been more rapid on lineages leading to Arabidopsis and Oryza compared with lineages leading to Populus and Vitis. The gamma paleohexiploidy event identified in the Arabidopsis, Populus and Vitis genomes is shown to have occurred after the divergence of all other known angiosperms from the lineage leading to Amborella.Conclusions: When placed in the context of a physical map, BAC end sequences representing just 5.4% of the Amborella genome have facilitated reconstruction of gene blocks that existed in the last common ancestor of all flowering plants. The Amborella genome is an invaluable reference for inferences concerning the ancestral angiosperm and subsequent genome evolution

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

A Pipeline Strategy for Grain Crop Domestication

In the interest of diversifying the global food system, improving human nutrition, and making agriculture more sustainable, there have been many proposals to domesticate wild plants or complete the domestication of semidomesticated orphan crops. However, very few new crops have recently been fully domesticated. Many wild plants have traits limiting their production or consumption that could be costly and slow to change. Others may have fortuitous preadaptations that make them easier to develop or feasible as high-value, albeit low-yielding, crops. To increase success in contemporary domestication of new crops, we propose a pipeline approach, with attrition expected as species advance through the pipeline. We list criteria for ranking domestication candidates to help enrich the starting pool with more preadapted, promising species. We also discuss strategies for prioritizing initial research efforts once the candidates have been selected: developing higher value products and services from the crop, increasing yield potential, and focusing on overcoming undesirable traits. Finally, we present new-crop case studies that demonstrate that wild species’ limitations and potential (in agronomic culture, shattering, seed size, harvest, cleaning, hybridization, etc.) are often only revealed during the early phases of domestication. When nearly insurmountable barriers were reached in some species, they have been (at least temporarily) eliminated from the pipeline. Conversely, a few species have moved quickly through the pipeline as hurdles, such as low seed weight or low seed number per head, were rapidly overcome, leading to increased confidence, farmer collaboration, and program expansion.Fil: DeHaan, Lee R.. The Land Institute; Estados UnidosFil: Van Tassel, David L.. The Land Institute; Estados UnidosFil: Anderson, James A.. University of Minnesota; Estados UnidosFil: Asselin, Sean R.. University of Manitoba; CanadáFil: Barnes, Richard. University of Minnesota; Estados UnidosFil: Baute, Gregory J.. University of British Columbia; CanadáFil: Cattani, Douglas J.. University of Manitoba; CanadáFil: Culman, Steve W.. Ohio State University; Estados UnidosFil: Dorn, Kevin M.. University of Minnesota; Estados UnidosFil: Hulke, Brent S.. United States Department of Agriculture. Agriculture Research Service; Estados UnidosFil: Kantar, Michael. University of British Columbia; CanadáFil: Larson, Steve. Forage and Range Research Laboratory; Estados UnidosFil: David Marks, M.. University of Minnesota; Estados UnidosFil: Miller, Allison J.. Saint Louis University; Estados UnidosFil: Poland, Jesse. Kansas State University; Estados UnidosFil: Ravetta, Damián Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Rude, Emily. University of Wisconsin; Estados UnidosFil: Ryan, Matthew R.. Cornell University; Estados UnidosFil: Wyse, Don. University of Minnesota; Estados UnidosFil: Zhang, Xiaofei. University of Minnesota; Estados Unido

Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children

Objectives: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis. Methods: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10-12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left-sided and proctosigmoiditis). Results: Mean age was 12.7 years; 49.6% (n = 212) were girls, and 83% (n = 351) were Caucasian. Severe total Mayo score was present in 28% (n = 120), mean PUCAI score was 49.8 ± 20.1, and 33% (n = 142) had severe mucosal disease with extensive involvement in 82% (n = 353). Classification and regression trees identified white blood cell count, erythrocyte sedimentation rate, and platelet count (PLT) as the set of 3 best blood laboratory tests to predict disease extent and severity. For mucosal severity, albumin (Alb) replaced PLT. Classification models for PUCAI and total Mayo provided sensitivity of at least 0.65 using standard clinical cut-points with misclassification rates of approximately 30%. Conclusions: A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores