Distinct Hot Spots Research Articles

Identifying overlap between humpback whale foraging grounds and the Antarctic krill fishery

The Antarctic krill fishery is the largest in the southern ocean, but currently operates without fine-scale information on whale movement and behavior. Using a multi-year dataset of satellite-tagged whales, as well as information on krill catch levels, we analyzed the spatial distribution of whales and fisheries effort within the small-scale management units defined by the Convention for the Conservation of Antarctic Marine Living Resources (CCAMLR). Using a Bayesian movement model to partition whale movement into traveling and area-restricted search states, we found that both whale behavior and krill catch effort were spatially clustered, with distinct hotspots of the whale activity in the Gerlache and southern Branfield Straits. These areas align with increases in krill fishing effort, and present potential areas of current and future conflict. We recommend that the Antarctic West and Bransfield Strait West management units merit particular attention when setting fine-scale catch limits and, more broadly, consideration as critical areas for krill predator foraging.

Understanding consumer preferences and demography in order to reduce the domestic trade in wild-caught birds

The wildlife trade is now one of the greatest threats to biodiversity, and birds are among the most commonly traded groups worldwide. The demand for pet birds is especially high in Indonesia, a country with many exploited, imperiled bird species. Finding solutions to the threat that trade poses for birds, and wildlife in general, requires an understanding of its socioeconomic dimensions. We examined consumer demography and preferences of 762 bird owners in Medan, Sumatra, focusing on the differences among owners of birds taken from the wild versus birds bred in captivity. We found that the vast majority of bird owners have at least one wild-caught bird. However, wild-caught bird ownership is not uniformly distributed across Medan; rather, there are distinct hotspots with high proportions of people with wild-caught birds. The main reasons for owning wild-caught birds are lack of access to and the high cost of captive-bred birds, and a perception that captive-bred birds do not sing as well as wild-caught ones. We conclude that captive-breeding programs could reduce the pressure on wild populations, especially if suppliers are able to produce relatively cheap captive-bred birds. However, the perceived poorer song quality of captive-bred individuals might be a problem for the captive breeding of some species, notably the White-rumped Shama, Copsychus malabaricus. Since many owners of this species compete in bird song competitions, establishing competition categories specifically for captive-bred shamas could promote captive-bred bird ownership. Tackling the problem of the wild bird trade in Indonesia and elsewhere will require consideration of both the economic and the social factors that underlie pet ownership.

Structural Analysis of Single Domain Antibodies Bound to a Second Neutralizing Hot Spot on Ricin Toxin's Enzymatic Subunit

Ricin toxin is a heterodimer consisting of RTA, a ribosome-inactivating protein, and RTB, a lectin that facilitates receptor-mediated uptake into mammalian cells. In previous studies, we demonstrated that toxin-neutralizing antibodies target four spatially distinct hot spots on RTA, which we refer to as epitope clusters I-IV. In this report, we identified and characterized three single domain camelid antibodies (VHH) against cluster II. One of these VHHs, V5E1, ranks as one of the most potent ricin-neutralizing antibodies described to date. We solved the X-ray crystal structures of each of the three VHHs (E1, V1C7, and V5E1) in complex with RTA. V5E1 buries a total of 1,133 Å2 of surface area on RTA and makes primary contacts with α-helix A (residues 18-32), α-helix F (182-194), as well as the F-G loop. V5E1, by virtue of complementarity determining region 3 (CDR3), may also engage with RTB and potentially interfere with the high affinity galactose-recognition element that plays a critical role in toxin attachment to cell surfaces and intracellular trafficking. The two other VHHs, E1 and V1C7, bind epitopes adjacent to V5E1 but display only weak toxin neutralizing activity, thereby providing structural insights into specific residues within cluster II that may be critical contact points for toxin inactivation.

Estimating the spatial distribution and locating hotspots of forest biomass from harvest residues and fire-damaged stands in Canada's managed forests

Strategies for increasing the mobilization of forest biomass supply chains for bioenergy production require continuous assessments of the spatial and temporal availability of biomass feedstock. Using remote sensing products at a 250-m pixel resolution, estimates of theoretical biomass availability from harvest residues and fire-killed trees were computed by combining Canada-wide maps of forest attributes (2001) and of yearly (2002–2011) fires and harvests. At the national scale, biomass availability was estimated at 47 ± 18 M ODT year−1 from fire-killed trees and at 14 ± 2 M ODT year−1 from harvest residues. Mean biomass densities in burned and harvested pixels were estimated at 34 ± 3.0 ODT ha−1 and at 24 ± 1.2 ODT ha−1, respectively. Mean biomass densities also varied dramatically among ecozones, from 14 ODT ha−1 to 206 ODT ha−1 and from 6 ODT ha−1 to 63 ODT ha−1 for burned and harvested pixels, respectively. Spatial averaging with a 100-km radius window shows distinct hotspots of biomass availability across Canada. The largest hotspots from fire-killed trees reached 3.6 M ODT year−1 in the Boreal Shield and the Boreal Plains ecozones of northern Alberta and Saskatchewan, where fires are large and frequent. The largest hotspots from harvest residues reached 1.2 M ODT year−1 in the Montane Cordillera ecozone of British Columbia. The use of spatially explicit remote sensing products yields estimates of theoretical biomass availability that are methodologically consistent across Canada. Future development should include validations with on-the-ground forest inventories as well as the factoring in of environmental, technical and economic considerations to implement operational biomass supply chains.

CO2 methanation: Optimal start‐up control of a fixed‐bed reactor for power‐to‐gas applications

Utilizing volatile renewable energy sources (e.g., solar, wind) for chemical production systems requires a deeper understanding of their dynamic operation modes. Taking the example of a methanation reactor in the context of power‐to‐gas applications, a dynamic optimization approach is used to identify control trajectories for a time optimal reactor start‐up avoiding distinct hot spot formation. For the optimization, we develop a dynamic, two‐dimensional model of a fixed‐bed tube reactor for carbon dioxide methanation which is based on the reaction scheme of the underlying exothermic Sabatier reaction mechanism. While controlling dynamic hot spot formation inside the catalyst bed, we prove the applicability of our methodology and investigate the feasibility of dynamic carbon dioxide methanation. © 2016 American Institute of Chemical Engineers AIChE J, 63: 23–31, 2017

Deep Sequencing Reveals Spatially Distributed Distinct Hot Spot Mutations in DICER1-Related Multinodular Goiter.

Nontoxic multinodular goiter (MNG) occurs frequently, but its genetic etiology is not well established. Familial MNG and MNG occurring with ovarian Sertoli-Leydig cell tumor are associated with germline DICER1 mutations. We recently identified second somatic DICER1 ribonuclease (RNase) IIIb mutations in two MNGs. The objective of the study was to investigate the occurrence of somatic DICER1 mutations and mutational clonality in MNG. MNGs from 15 patients (10 with and five without germline DICER1 mutations) were selected based on tissue availability. Core biopsies/scrapings (n = 70) were obtained, sampling areas of follicular hyperplasia, hyperplasia within colloid pools, unremarkable thyroid parenchyma, and areas of thyroid parenchyma, not classified. After capture with a Fluidigm access array, the coding sequence of DICER1 was deep sequenced using DNA from each core/scraping. All germline DICER1-mutated cases were found to harbor at least one RNase III mutation. Specifically, we identified 12 individually distinct DICER1 RNase IIIb hot spot mutations in 32 of the follicular hyperplasia or hyperplasia within colloid pools cores/scrapings. These mutations are predicted to affect the metal-ion binding residues at positions p.Glu1705, p.Asp1709, p.Gly1809, p.Asp1810, and p.Glu1813. Somatic RNase IIIb mutations were identified in the 10 DICER1 germline mutated MNGs as follows: two cases contained one somatic mutation, five cases contained two mutations, and three cases contained three distinct somatic hot spot mutations. No RNase IIIb mutations were identified in the MNGs from individuals without germline DICER1 mutations. This study demonstrates that nodules within MNG occurring in DICER1 syndrome are associated with spatially distributed somatic DICER1 RNase IIIb mutations.

Fragment Screening of RORγt Using Cocktail Crystallography: Identification of Simultaneous Binding of Multiple Fragments.

The retinoic-acid-related orphan receptor γ t (RORγt), as a master regulator of Th17 cell pathology, has become an attractive target for small-molecule drug discovery for the treatment of Th17-cell-related autoimmune diseases. A crystallographic fragment screening was carried out for RORγt using the ligand binding domain. An overall hit rate of 5.5 % was obtained by screening 384 compounds in 96 cocktails. Five distinct hotspots were identified, and four regions of anchoring polar interactions were observed. In addition, significant induced fit was found for the binding of several fragments. Strikingly, a simultaneous binding of three fragments was revealed which presents interesting features including π-π stacking, multiple hydrogen bonds to the protein, and significant induced fit. Overall, the results offer a complete mapping of the ligand binding pocket and provide valuable inspiration in structure-based design for RORγt lead generation and optimization. The crystallographic screening also resulted in fragment hits that bind at the surface away from the ligand binding pocket. This surface site is near the plausible dimer interface by analogy with other nuclear receptor systems, which can provide initial hints to explore alternative ways to modulate RORγt through protein-protein interactions.

Abstract 2390: The polyclonal nature of multinodular goitre revealed by DICER1 sequencing

Abstract Nontoxic multinodular goitre (MNG) occurs frequently in the general population and is characterised by nodular enlargement of the thyroid gland. In 2011, Rio Frio et al discovered that familial MNG and MNG occurring with Sertoli-Leydig cell tumours were associated with germ-line mutations in the microRNA-processing gene, DICER1. We recently reported the first instance of biallelic DICER1 mutations in an MNG. This prompted us to further investigate the role of DICER1 mutations in MNG pathogenesis. Given that MNG may either be a monoclonal or polyclonal disease, we set out to investigate whether the molecular landscape was correspondingly heterogeneous. We obtained core biopsies (n = 27) from 9 MNGs. 1mm cores were excised from morphologically distinct regions, including from areas of follicular hyperplasia (FH), hyperplasia within colloid pools (HC) and/or otherwise unremarkable areas. DNA extracted from each core was processed using a custom Fluidigm Access Array followed by deep sequencing. We focused our investigation on the RNase IIIb domain of DICER1 to identify known hotspot mutations. All mutations were validated by Sanger sequencing. We identified 6 individually distinct DICER1 RNase IIIb hotspot mutations in 14 (of 27) cores consisting of FH or HC (Table 1). These mutations affected the metal-ion binding residues at positions 1705, 1709, 1810 & 1813. Two MNGs that arose in individuals without germ-line DICER1 mutations did not carry any RNase IIIb hits. Of the remaining 7 germ-line DICER1-mutated cases, 2 carried 1 RNase IIIb mutation; 4 carried 2 different RNase IIIb mutations and one case did not carry any successfully-validated RNase IIIb mutations. We demonstrate that spatial heterogeneity of RNase IIIb DICER1 mutations exists in MNG. We postulate that cyclic hyperplasia followed by regression over time in response to external stimuli, particularly in germ-line DICER1 mutation carriers, contributes to the polyclonal accumulation of RNase IIIb mutations in MNG. Table 1:DICER1 RNase IIIb Mutation FrequenciesCaseGerm-line DICER1 StatusMorphologyc.5113G>A p.E1705Kc.5125G>A p.D1709Nc.5126A>G p.D1709Gc.5428G>T p.D1810Yc.5429A>T p.D1810Vc.5437G>C p.E1813Q1PositiveHC41.7–––––FH–––––22.12PositiveFH––––––UR––––––HC––––––UR––––––HC––Sanger–––HC––Sanger–––3PositiveHC––––29.2–FH–43.7––––FH–28.8––––4PositiveHC––30.6–––UR––––––HC––33.1–––FH–––52.3––5PositiveHC––––––HC with FH––––––6PositiveFH–––––39.3FH–––––13.1FH––––––7PositiveFH–––41.8––FH28.0–––––8NegativeFH––––––HC––––––9NegativeFH––––––PTC––––––FH––––––Abbreviations: FH, follicular hyperplasia; HC, hyperplasia within colloid pools; UR, unremarkable; PTC, papillary thyroid ca. Notes: Each row corresponds to a separate core. Mutant allele frequencies are indicated in each cell (all >10%); ‘‘–’’ indicates mutation not observed in core DNA; Sanger, indicates mutations previously identified in an independent PCR from bulk MNG DNA, tested by Sanger sequencing. All Fluidigm positives were confirmed by Sanger sequencing from the same DNA that was used to do the Fluidigm analysis. Citation Format: Leanne de Kock, Ismaël Bah, Mona Wu, John R. Priest, Jiannis Ragoussis, William D. Foulkes. The polyclonal nature of multinodular goitre revealed by DICER1 sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2390.

Time variability of Io's volcanic activity from near-IR adaptive optics observations on 100 nights in 2013–2015

Jupiter’s moon Io is a dynamic target, exhibiting extreme and time-variable volcanic activity powered by tidal forcing from Jupiter. We have conducted a campaign of high-cadence observations of Io with the goal of characterizing its volcanic activity. Between Aug 2013 and the end of 2015, we imaged Io on 100 nights in the near-infrared with adaptive optics on the Keck and Gemini N telescopes, which resolve emission from individual volcanic hot spots. During our program, we made over 400 detections of 48 distinct hot spots, some of which were detected 30+ times. We use these observations to derive a timeline of global volcanic activity on Io, which exhibits wide variability from month to month. The timelines of thermal activity at individual volcanic centers have geophysical implications, and will permit future characterization by others. We evaluate hot spot detection limits and give a simple parameterization of the minimum detectable intensity as a function of emission angle, which can be applied to other analyses.We detected three outburst eruptions in August 2013, but no other outburst-scale events were observed in the subsequent ∼90 observations. Either the cluster of events in August 2013 was a rare occurrence, or there is a mechanism causing large events to occur closely-spaced in time. We also detected large eruptions (though not of outburst scale) within days of one another at Kurdalagon Patera and Sethlaus/Gabija Paterae in 2015. As was also seen in the Galileo dataset, the hot spots we detected can be separated into two categories based on their thermal emission: those that are persistently active for 1 year or more at moderate intensity, and those that are only briefly active, are time-variable, and often reach large intensities. A small number of hot spots in the latter category appear and subside in a matter of days, reaching particularly high intensities; although these are not bright enough to qualify as outbursts, their thermal signatures follow the same pattern, suggesting that a similar mechanism may be responsible for these events though at a smaller scale.Two eruptions seen at Kurdalagon Patera in January and April 2015 occurred simultaneously with a brightening of the neutral cloud and plasma torus which are sourced from Io’s atmosphere. A plume at Kurdalagon Patera, such as was seen by New Horizons in 2007, could have been responsible for the influx of material that caused these brightenings.

High-Resolution Mapping of Crossover and Non-crossover Recombination Events by Whole-Genome Re-sequencing of an Avian Pedigree.

Recombination is an engine of genetic diversity and therefore constitutes a key process in evolutionary biology and genetics. While the outcome of crossover recombination can readily be detected as shuffled alleles by following the inheritance of markers in pedigreed families, the more precise location of both crossover and non-crossover recombination events has been difficult to pinpoint. As a consequence, we lack a detailed portrait of the recombination landscape for most organisms and knowledge on how this landscape impacts on sequence evolution at a local scale. To localize recombination events with high resolution in an avian system, we performed whole-genome re-sequencing at high coverage of a complete three-generation collared flycatcher pedigree. We identified 325 crossovers at a median resolution of 1.4 kb, with 86% of the events localized to <10 kb intervals. Observed crossover rates were in excellent agreement with data from linkage mapping, were 52% higher in male (3.56 cM/Mb) than in female meiosis (2.28 cM/Mb), and increased towards chromosome ends in male but not female meiosis. Crossover events were non-randomly distributed in the genome with several distinct hot-spots and a concentration to genic regions, with the highest density in promoters and CpG islands. We further identified 267 non-crossovers, whose location was significantly associated with crossover locations. We detected a significant transmission bias (0.18) in favour of ‘strong’ (G, C) over ‘weak’ (A, T) alleles at non-crossover events, providing direct evidence for the process of GC-biased gene conversion in an avian system. The approach taken in this study should be applicable to any species and would thereby help to provide a more comprehensive portray of the recombination landscape across organism groups.

Effect of climate data on simulated carbon and nitrogen balances for Europe

AbstractIn this study, we systematically assess the spatial variability in carbon and nitrogen balance simulations related to the choice of global circulation models (GCMs), representative concentration pathways (RCPs), spatial resolutions, and the downscaling methods used as calculated with LPJ‐GUESS. We employed a complete factorial design and performed 24 simulations for Europe with different climate input data sets and different combinations of these four factors. Our results reveal that the variability in simulated output in Europe is moderate with 35.6%–93.5% of the total variability being common among all combinations of factors. The spatial resolution is the most important factor among the examined factors, explaining 1.5%–10.7% of the total variability followed by GCMs (0.3%–7.6%), RCPs (0%–6.3%), and downscaling methods (0.1%–4.6%). The higher‐order interactions effect that captures nonlinear relations between the factors and random effects is pronounced and accounts for 1.6%–45.8% to the total variability. The most distinct hot spots of variability include the mountain ranges in North Scandinavia and the Alps, and the Iberian Peninsula. Based on our findings, we advise to conduct the application of models such as LPJ‐GUESS at a reasonably high spatial resolution which is supported by the model structure. There is no notable gain in simulations of ecosystem carbon and nitrogen stocks and fluxes from using regionally downscaled climate in preference to bias‐corrected, bilinearly interpolated CMIP5 projections.

Groundwater, Acid and Carbon Dioxide Dynamics Along a Coastal Wetland, Lake and Estuary Continuum

Coastal wetlands are hotspots for biodiversity and biological productivity, yet the hydrology and carbon cycling within these systems remains poorly understood due to their complex nature. By using a novel spatiotemporal approach, this study quantified groundwater discharge and the related inputs of acidity and CO2 along a continuum of a modified coastal acid sulphate soil (CASS) wetland, a coastal lake and an estuary under highly contrasting hydrological conditions. To increase the resolution of spatiotemporal data and advance upon previous methodologies, we relied on automated observations from four simultaneous time-series stations to develop multiple radon mass balance models to estimate groundwater discharge and related groundwater inputs of acidity and dissolved inorganic carbon (DIC), along with surface water to atmosphere CO2 fluxes. Spatial surveys indicated distinct acid hotspots with minimum surface water pH of 2.91 (dry conditions) and 2.67 (flood conditions) near a non-remediated (drained) CASS area. Under flood conditions, groundwater discharge accounted for ∼14.5 % of surface water entering the lake. During the same period, acid discharge from the acid sulphate soil section of the continuum produced ∼4.8 kg H2SO4 ha−1 day−1, a rate much higher than previous studies in similar systems. During baseflow conditions, the low pH water was rapidly buffered within the estuarine lake, with the pH increasing from 4.22 to 6.07 over a distance of ∼250 m. The CO2 evasion rates within the CASS were extremely high, averaging 2163 ± 125 mmol m−2 day−1 in the dry period and 4061 ± 259 mmol m−2 day−1 under flood conditions. Groundwater input of DIC could only account for 0.4 % of this evasion in the dry conditions and ∼5 % during the flood conditions. We demonstrated that by utilising a spatiotemporal (multiple time-series stations) approach, the study was able to isolate distinct zones of differing hydrology and biogeochemistry, whilst providing more reasonable groundwater acid input estimates and air–water CO2 flux estimates than some traditional sampling designs. This study highlights the notion that modified CASS wetlands can release large amounts of CO2 to the atmosphere because of high groundwater acid inputs and extremely low surface water pH.

Differential climate impacts for policy-relevant limits to global warming: the case of 1.5 °C and 2 °C

Abstract. Robust appraisals of climate impacts at different levels of global-mean temperature increase are vital to guide assessments of dangerous anthropogenic interference with the climate system. The 2015 Paris Agreement includes a two-headed temperature goal: "holding the increase in the global average temperature to well below 2 °C above pre-industrial levels and pursuing efforts to limit the temperature increase to 1.5 °C". Despite the prominence of these two temperature limits, a comprehensive overview of the differences in climate impacts at these levels is still missing. Here we provide an assessment of key impacts of climate change at warming levels of 1.5 °C and 2 °C, including extreme weather events, water availability, agricultural yields, sea-level rise and risk of coral reef loss. Our results reveal substantial differences in impacts between a 1.5 °C and 2 °C warming that are highly relevant for the assessment of dangerous anthropogenic interference with the climate system. For heat-related extremes, the additional 0.5 °C increase in global-mean temperature marks the difference between events at the upper limit of present-day natural variability and a new climate regime, particularly in tropical regions. Similarly, this warming difference is likely to be decisive for the future of tropical coral reefs. In a scenario with an end-of-century warming of 2 °C, virtually all tropical coral reefs are projected to be at risk of severe degradation due to temperature-induced bleaching from 2050 onwards. This fraction is reduced to about 90 % in 2050 and projected to decline to 70 % by 2100 for a 1.5 °C scenario. Analyses of precipitation-related impacts reveal distinct regional differences and hot-spots of change emerge. Regional reduction in median water availability for the Mediterranean is found to nearly double from 9 % to 17 % between 1.5 °C and 2 °C, and the projected lengthening of regional dry spells increases from 7 to 11 %. Projections for agricultural yields differ between crop types as well as world regions. While some (in particular high-latitude) regions may benefit, tropical regions like West Africa, South-East Asia, as well as Central and northern South America are projected to face substantial local yield reductions, particularly for wheat and maize. Best estimate sea-level rise projections based on two illustrative scenarios indicate a 50 cm rise by 2100 relative to year 2000-levels for a 2 °C scenario, and about 10 cm lower levels for a 1.5 °C scenario. In a 1.5 °C scenario, the rate of sea-level rise in 2100 would be reduced by about 30 % compared to a 2 °C scenario. Our findings highlight the importance of regional differentiation to assess both future climate risks and different vulnerabilities to incremental increases in global-mean temperature. The article provides a consistent and comprehensive assessment of existing projections and a good basis for future work on refining our understanding of the difference between impacts at 1.5 °C and 2 °C warming.

Abstract IA12: Mechanisms of tumorigenesis due to somatic mutations in DICER1 and DROSHA in childhood kidney cancers

Abstract Wilms tumor is the most common pediatric kidney cancer and the fourth most common childhood cancer overall. Wilms tumor is treated with a combination of surgery, chemotherapy, and radiation, and, while most children are cured, patients suffer adverse late effects of therapy and survival remains poor in those with advanced-stage disease. Known driver mutations (in WT1, WTX, and β-catenin) account for only one-third of Wilms tumor cases. To better define the genomic landscape of Wilms tumor, we performed whole-exome sequencing of 44 Wilms tumors to identify somatic mutations. Through this approach, we identified recurrent somatic mutations in MYCN, DROSHA, and DICER1, which were mutually exclusive with known Wilms tumor driver mutations in WT1 and β-catenin. DROSHA and DICER1 somatic hotspot mutations occur at or near critical metal-binding residues in RNase III domains and partially or completely disrupt enzyme activity. Examination of miRNA expression in tumors, in vitro processing assays, and genomic editing in human cells demonstrate that DICER1 and DROSHA mutations influence miRNA processing through distinct mechanisms. While DICER1 RNase IIIB mutations preferentially impair processing of miRNAs that derive from the 5′ arm of pre-miRNA hairpins, DROSHA RNase IIIB mutations globally inhibit miRNA biogenesis through a dominant-negative mechanism. Despite their distinct mechanisms of action, DROSHA and DICER1 mutations result in decreased expression of several common tumor-suppressing miRNAs, including multiple members of the let-7 and miR-15/16 families. We also identified a patient carrying a germline DICER1 loss-of-function allele who subsequently developed multiple malignancies with distinct DICER1 RNase IIIB somatic hotspot mutations, suggesting that DICER1 can act as both a tumor-suppressor and an oncogene depending on the nature of the mutation. These results provide new insights into the mechanisms through which mutations in miRNA biogenesis components reprogram miRNA expression in human cancer and suggest that mutations causing impairment of miRNA processing define a distinct subclass of Wilms tumors. Citation Format: Kenneth S. Chen, Dinesh Rakheja, Yangjian Liu, Abhay A. Shukla, Joshua T. Mendell, James F. Amatruda. Mechanisms of tumorigenesis due to somatic mutations in DICER1 and DROSHA in childhood kidney cancers. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr IA12.

Epidemiology & risk factors of scrub typhus in south India.

Background & objectives:Scrub typhus is a major public health threat in South and Southeastern Asian countries including India. Understanding local patterns of disease and factors that place individuals at risk is pivotal to future preventive measures against scrub typhus. The primary aim of this study was to identify specific epidemiological and geographical factors associated with an increased risk of developing scrub typhus in this region.Methods:We mapped 709 patients from Tamil Nadu, Andhra Pradesh and Telangana who were admitted to the Christian Medical College (CMC) Hospital, Vellore, Tamil Nadu, India, for the period 2006-2011, assessed seasonality using monthly counts of scrub typhus cases, and conducted a case-control study among a subset of patients residing in Vellore.Results:The geographic distribution of cases at CMC Hospital clusters around the Tamil Nadu-Andhra Pradesh border. However, distinct hotspots clearly exist distal to this area, near Madurai and the coast in Tamil Nadu, and in the Northeast of Andhra Pradesh. Seasonally, the highest numbers of cases were observed in the cooler months of the year, i.e. September to January. In the case-control analysis, cases were more likely to be agricultural laborers (OR 1.79, 95% CI 1.01 - 3.15), not wear a shirt at home (OR 4.23, 95% CI 1.12 - 16.3), live in houses adjacent to bushes or shrubs (OR 1.95, 95% CI 1.08 - 3.53), and live in a single room home (OR 1.75, 95% CI 1.02 - 3.01). On binary logistic regression, the first three of these variables were statistically significant.Interpretation & conclusions:With the growing number of cases detected in India, scrub typhus is fast emerging as a public health threat and further research to protect the population from this deadly infection is essential. Health education campaigns focusing on the agricultural workers of Southern India, especially during the cooler months of the year, can serve as an important public health measure to control infection.

US colorectal cancer death rates decline except in 3 geographic “hot spots”

Although most of the United States has experienced large declines in colorectal cancer death rates, 3 geographic areas have been exceptions to this trend according to the results of a new study: the lower Mississippi Delta, west-central Appalachia, and eastern Virginia/North Carolina. The study, led by Rebecca Siegel, MPH, director of surveillance information for the American Cancer Society, involved the use of a geospatial software tool to identify areas of very low rates of colorectal cancer deaths (cold spots) and very high rates (hot spots). For the latter, death rates were plotted from 1970 to 2011, and rate ratios were calculated to compare trends over time between them and the rest of the country. Siegel and colleagues identifi ed the 3 distinct hot spots, including 94 counties of the lower Mississippi Delta, 107 counties of west-central Appalachia, and 37 counties of eastern Virginia/North Carolina. Th e lower Mississippi Delta hot spot had colorectal cancer death rates that were 40% higher than those of the non–hot spot areas in the country from 2009 to 2011. Rates in the hot spots in west-central Appalachia and eastern Virginia/North Carolina were 18% and 9% higher, respectively, than those of the non–hot spot areas during the same time period. For black men in the lower Mississippi Delta, the colorectal cancer death rate increased steadily by 3.5% per year between 1970 and 1990, and it has since remained unchanged. The authors also noted that in the 1970s, death rates in the lower Mississippi Delta were 18% lower than the average colorectal cancer death rates in the country but that the rates caught up with the rest of the nation in approximately 1990. Siegel adds that although colorectal cancer death rates have started to decline in the lower Mississippi Delta for most population groups, they remain stagnant for black men. Th ese areas are “lowhanging fruit” for colorectal cancer interventions, she says.

Where Can Colorectal Cancer Screening Interventions Have the Most Impact?

Although colorectal cancer death rates in the United States have declined by half since 1970, large geographic disparities persist. Spatial identification of high-risk areas can facilitate targeted screening interventions to close this gap. We used the Getis-Ord Gi* statistic within ArcGIS to identify contemporary colorectal cancer "hotspots" (spatial clusters of counties with high rates) based on county-level mortality data from the national vital statistics system. Hotspots were compared with the remaining aggregated counties (non-hotspot United States) by plotting trends from 1970 to 2011 and calculating rate ratios (RR). Trends were quantified using joinpoint regression. Spatial mapping identified three distinct hotspots in the contemporary United States where colorectal cancer death rates were elevated. The highest rates were in the largest hotspot, which encompassed 94 counties in the Lower Mississippi Delta [Arkansas (17), Illinois (16), Kentucky (3), Louisiana (6), Mississippi (27), Missouri (15), and Tennessee (10)]. During 2009 to 2011, rates here were 40% higher than the non-hotspot United States [RR, 1.40; 95% confidence interval (CI), 1.34-1.46], despite being 18% lower during 1970 to 1972 (RR, 0.82; 95% CI, 0.78-0.86). The elevated risk was similar in blacks and whites. Notably, rates among black men in the Delta increased steadily by 3.5% per year from 1970 to 1990, and have since remained unchanged. Rates in hotspots in west central Appalachia and eastern Virginia/North Carolina were 18% and 9% higher, respectively, than the non-hotspot United States during 2009 to 2011. Advanced spatial analysis revealed large pockets of the United States with excessive colorectal cancer death rates. These well-defined areas warrant prioritized screening intervention.

Accidents in the Energy Sector and Energy Infrastructure Attacks in the Context of Energy Security

The risks of technological accidents in the energy sector and their potentially disastrous effects have been analyzed over the past decades, and are nowadays generally recognized to constitute a key factor in an encompassing assessment of energy security. In contrast, the issue of intentional attacks on energy infrastructures has received increased attentionmore recently, particularly due to growing dependence of energy imports fromand transit routes through regions considered less reliable and politically stable. Both types of risks, however, illuminate different vulnerabilities. Therefore, the focus of the present analysis was on these two risk categories: accidents and intentional attacks in the energy sector. Risk assessment resultswere based on quantitative data from the databases ENSAD (Energy-related Severe Accident Database) and EIAD (Energy Infrastructure Attack Database). Evaluations examined similarities and differences between technological accidents and intentional attacks in terms of frequencies and consequences, considering time-series trends and regional patterns. A key difference is that accidents are typically rare and independent events, whereas intentional attacks are often multiple events and concentrated both in time and space, resulting in distinct hotspots. Concerning consequences, the severity distribution for accidents generally stretches over a broad range, with low-probability high-consequence events being an important factor of both energy chain performance and as a measure of risk aversion. On the other hand, these types of consequences are usually less important for intentional attacks because targeted energy infrastructures are often of “linear” nature (e.g. pipelines and transmission lines) that are difficult to protect and usually lead through remote areas with low population density. However, when frequently attacked substantial business and supply disruptions can occur. In summary, the joint analysis of accidents and intentional attacks provides a comprehensive and complementary approach on two types of risks that have rather different properties, but are essential in an energy security perspective.

Identifying key habitats for the conservation of Chilean dolphins in the fjords of southern Chile

Abstract In the face of environmental degradation, animals with limited plasticity are likely to be the most vulnerable. Habitat selection by the threatened, endemic Chilean dolphin (Cephalorhynchus eutropia) was investigated in the northern Patagonian fjords, an area of extraordinary biological productivity. Generalized additive models were undertaken to assess the ecological determinants of Chilean dolphin spatial distribution and habitat selection. Data were collected from dedicated fine‐scale marine surveys conducted during the austral summer of 2007, 2008 and 2009 Modelling techniques provide strong support for Chilean dolphins aggregating in distinct hotspots, preferring shallow water, near rivers and in areas where the influence of tidal regime is greater. The preference for coastal shallow waters and river influenced habitats by Chilean dolphins puts them in direct conflict with a growing aquaculture industry and hydropower projects. The models predict areas of high densities of Chilean dolphins and excluding these areas from new developments would provide clear protection to the habitat most important to this poorly known endemic Chilean species. Copyright © 2015 John Wiley &amp; Sons, Ltd.

Temporal and spatial regulation of translation in the mammalian oocyte via the mTOR-eIF4F pathway.

The fully grown mammalian oocyte is transcriptionally quiescent and utilizes only transcripts synthesized and stored during early development. However, we find that an abundant RNA population is retained in the oocyte nucleus and contains specific mRNAs important for meiotic progression. Here we show that during the first meiotic division, shortly after nuclear envelope breakdown, translational hotspots develop in the chromosomal area and in a region that was previously surrounded the nucleus. These distinct translational hotspots are separated by endoplasmic reticulum and Lamin, and disappear following polar body extrusion. Chromosomal translational hotspots are controlled by the activity of the mTOR–eIF4F pathway. Here we reveal a mechanism that—following the resumption of meiosis—controls the temporal and spatial translation of a specific set of transcripts required for normal spindle assembly, chromosome alignment and segregation.