How do pesticides impact soil microbial structure and functioning?

Pesticides are used worldwide and exhibit a plethora of different modes of action against a wide spectrum of organisms. Therefore, before they can be marketed they have to be tested against certain standardised regulations. These include the Food and Environment Protection Act 1985 (FEPA), the Control of Pesticides Regulations 1986 (COPR), and more recently the European Council Directive 1991 91/414 and the Plant Protection Products Regulations 1991 (PPPR). However, the current tests used to determine pesticide impacts on microorganisms as detailed by the OECD focus on only broadscale analytical methods that may mask more subtle effects that may still be ecologically significant. Therefore, this project aimed to determine the effects of a widely-used model pesticide, azoxystrobin on both target and non-target microbial communities across different trophic levels. The techniques used to perform this included broad- (soil microbial biomass and soil dehydrogenase activity) and fine-scale (T-RFLP, cloning/sequencing, and qPCR) analytical methods. The results of these analyses showed that the application of azoxystrobin had a significant, concentration-dependent impact on soil dehydrogenase activity whilst biomass was unaffected. The molecular analyses showed that azoxystrobin significantly impacted fungal community structure, diversity and gene copy number. Additionally, pesticide application significantly altered nematode community structure and general eukaryotic diversity. Soil and liquid culture enrichments showed that azoxystrobin degradation can be enhanced following repeated applications and enabled the isolation of two degrader organisms with sequence homologies to a Cupriavidus sp. and a Rhodanobacter sp. Further work showed that sequential enrichments with azoxystrobin also conferred cross-enhanced degradative abilities for three other strobilurin fungicides: pyraclostrobin, kresoxim methyl and trifloxystrobin. The work performed in this thesis served to illustrate how the current OECD test procedures may benefit from the incorporation of finer-scale molecular methods into its tests, as well as how difficult the task can be to produce compounds that persist in the environment long enough to perform their required function, but do not have significant deleterious impacts on non-target organisms when present.EThOS - Electronic Theses Online ServiceBiotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)GBUnited Kingdo

Enhancing safety-critical message dissemination in WAVE

The competing priorities of safety-critical messages and infotainment messages present a significant challenge when designing effective IEEE 1609.4 protocol enhancements. In this paper, we investigate the latency reduction provided by an additional CCH check back midway through the Service Channel interval. Mathematical analysis and experimentation using simulations have shown that this method results in significant latency reduction. The maximum transmission delay for safety-critical messages can be reduced by approximately half whilst only reducing the Service Channel capacity by one quarter. As the work progresses, we will optimise the duration of the check back to find the best compromise between safety and infotainment

Gristhorpe Man: an Early Bronze Age log-coffin burial scientifically defined

© 2010 Antiquity PublicationsA log-coffin excavated in the early nineteenth century proved to be well enough preserved in the early twenty-first century for the fill armoury of modern scientific investigation to give its occupants and contents new identity, new origins and a new date. In many ways the interpretation is much the same as before: a local big man buried looking out to sea. Modern analytical techniques can create a person more real, more human and more securely anchored in history. This research team shows how.The project has been funded by grants from the British Academy, British Association for the Advancement of Science, Natural Environment Research Council, Royal Archaeological Institute and Scarborough Museums Trust. CJK’s participation in this project was funded by a Leverhulme Research Fellowship (RF/6/RFG/2008/0253)

Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry

Abstract With improved survivorship in medulloblastoma, there has been an increasing incidence of late complications. To date, no studies have specifically addressed the risk of radiation-associated diffuse intrinsic pontine glioma (DIPG) in medulloblastoma survivors. Query of the International DIPG Registry identified six cases of DIPG with a history of medulloblastoma treated with radiotherapy. All patients underwent central radiologic review that confirmed a diagnosis of DIPG. Six additional cases were identified in reports from recent cooperative group medulloblastoma trials (total n = 12; ages 7 to 21 years). From these cases, molecular subgrouping of primary medulloblastomas with available tissue (n = 5) revealed only non-WNT, non-SHH subgroups (group 3 or 4). The estimated cumulative incidence of DIPG after post-treatment medulloblastoma ranged from 0.3–3.9%. Posterior fossa radiation exposure (including brainstem) was greater than 53.0 Gy in all cases with available details. Tumor/germline exome sequencing of three radiation-associated DIPGs revealed an H3 wild-type status and mutational signature distinct from primary DIPG with evidence of radiation-induced DNA damage. Mutations identified in the radiation-associated DIPGs had significant molecular overlap with recurrent drivers of adult glioblastoma (e.g. NRAS, EGFR, and PTEN), as opposed to epigenetic dysregulation in H3-driven primary DIPGs. Patients with radiation-associated DIPG had a significantly worse median overall survival (median 8 months; range 4–17 months) compared to patients with primary DIPG. Here, it is demonstrated that DIPG occurs as a not infrequent complication of radiation therapy in survivors of pediatric medulloblastoma and that radiation-associated DIPGs may present as a poorly-prognostic distinct molecular subgroup of H3 wild-type DIPG. Given the abysmal survival of these cases, these findings provide a compelling argument for efforts to reduce exposure of the brainstem in the treatment of medulloblastoma. Additionally, patients with radiation-associated DIPG may benefit from future therapies targeted to the molecular features of adult glioblastoma rather than primary DIPG.https://deepblue.lib.umich.edu/bitstream/2027.42/145180/1/40478_2018_Article_570.pd

Challenges in managing urinary tract infection and the potential of a point-of-care test guided care in primary care: an international qualitative study

Background Little is known about clinicians’ experiences of using a point-of-care test (POCT) to inform management of urinary tract infection (UTI) in general practice. Aim To explore experiences of using the Flexicult test to inform management of UTI and views on requirements for an optimal POCT to inform successful implementation. Design & setting Telephone interviews with 35 primary care clinicians and healthcare professionals in Wales, England, Spain, and the Netherlands, who had participated in a trial of the Flexicult POCT for UTI based on urine culture. Method Thematic analysis of semi-structured interviews. Results Most primary care clinicians interviewed agreed on the need for a POCT in UTI management, and that the Flexicult POCT delivered quicker results than laboratory results used in usual care, reassured patients, boosted their confidence in decision-making, and reminded them about antibiotic stewardship. However, clinicians also reported difficulties in interpreting results, limitations on when the Flexicult could be used, and concerns that testing all patients would strain care delivery and prolong patient discomfort when delaying decisions until a non-rapid POCT result was available. An optimal POCT would produce more rapid results, and be reliable and easy to use. Uptake into routine care would be enhanced by: clear guidance on which patients should be tested; training for interpreting ‘grey area’ results; reiterating that even ‘straightforward’ cases might be better managed with a test; clear messages about stopping unnecessary antibiotics versus completing a course; and better self-management strategies to accompany implementation of delayed, or non-prescription of, antibiotics. Conclusion Primary care clinicians believe that POCT tests could play a useful role in the management of UTI and gave clear recommendations for successful implementation

Validation of TOI-1221 b: A warm sub-Neptune exhibiting TTVs around a Sun-like star

We present a validation of the long-period ($91.68278^{+0.00032}_{-0.00041}$ days) transiting sub-Neptune planet TOI-1221 b (TIC 349095149.01) around a Sun-like (m$_{\rm V}$=10.5) star. This is one of the few known exoplanets with period >50 days, and belongs to the even smaller subset of which have bright enough hosts for detailed spectroscopic follow-up. We combine TESS light curves and ground-based time-series photometry from PEST (0.3~m) and LCOGT (1.0~m) to analyze the transit signals and rule out nearby stars as potential false positive sources. High-contrast imaging from SOAR and Gemini/Zorro rule out nearby stellar contaminants. Reconnaissance spectroscopy from CHIRON sets a planetary scale upper mass limit on the transiting object (1.1 and 3.5 M$_{\rm Jup}$ at 1$\sigma$ and 3$\sigma$, respectively) and shows no sign of a spectroscopic binary companion. We determine a planetary radius of $R_{\rm p} = 2.91^{+0.13}_{-0.12} R_{\oplus}$, placing it in the sub-Neptune regime. With a stellar insolation of $S = 6.06^{+0.85}_{-0.77}\ S_{\oplus}$, we calculate a moderate equilibrium temperature of $T_{\rm eq} =$ 440 K, assuming no albedo and perfect heat redistribution. We find a false positive probability from TRICERATOPS of FPP $= 0.0014 \pm 0.0003$ as well as other qualitative and quantitative evidence to support the statistical validation of TOI-1221 b. We find significant evidence (>$5\sigma$) of oscillatory transit timing variations, likely indicative of an additional non-transiting planet.Comment: 17 pages, 9 figures, 4 table

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

TESS Discovery of Twin Planets near 2:1 Resonance around Early M-Dwarf TOI 4342

With data from the Transiting Exoplanet Survey Satellite (TESS), we showcase improvements to the MIT Quick-Look Pipeline (QLP) through the discovery and validation of a multi-planet system around M-dwarf TOI 4342 ($T_{mag}=11.032$, $M_* = 0.63 M_\odot$, $R_* = 0.60 R_\odot$, $T_{eff} = 3900$ K, $d = 61.54$ pc). With updates to QLP, including a new multi-planet search, as well as faster cadence data from TESS' First Extended Mission, we discovered two sub-Neptunes ($R_b = 2.266_{-0.038}^{+0.038} R_\oplus$ and $R_c = 2.415_{-0.040}^{+0.043} R_\oplus$; $P_b$ = 5.538 days and $P_c$ = 10.689 days) and validated them with ground-based photometry, spectra, and speckle imaging. Both planets notably have high transmission spectroscopy metrics (TSMs) of 36 and 32, making TOI 4342 one of the best systems for comparative atmospheric studies. This system demonstrates how improvements to QLP, along with faster cadence Full-Frame Images (FFIs), can lead to the discovery of new multi-planet systems.Comment: accepted for publication in A

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo