Extracellular vesicles in urological malignancies

Extracellular vesicles (EVs) are small lipid bound structures released from cells containing bioactive cargoes. Both the type of cargo and amount loaded varies compared to that of the parent cell. The characterisation of EVs in cancers of the male urogenital tract has identified several cargoes with promising diagnostic and disease monitoring potential. EVs released by cancers of the male urogenital tract promote cell-to-cell communication, migration, cancer progression and manipulate the immune system promoting metastasis by evading the immune response. Their use as diagnostic biomarkers represents a new area of screening and disease detection, potentially reducing the need for invasive biopsies. Many validated EV cargoes have been found to have superior sensitivity and specificity than current diagnostic tools currently in use. The use of EVs to improve disease monitoring and develop novel therapeutics will enable clinicians to individualise patient management in the exciting era of personalised medicine

The Galactic cosmic ray intensity at the evolving Earth and young exoplanets

Cosmic rays may have contributed to the start of life on the Earth. Here, we investigate the evolution of the Galactic cosmic ray spectrum at the Earth from ages t = 0.6−6.0 Gyr. We use a 1D cosmic ray transport model and a 1.5D stellar wind model to derive the evolving wind properties of a solar-type star. At t=1 Gyr, approximately when life is thought to have begun on the Earth, we find that the intensity of ∼GeV Galactic cosmic rays would have been ∼10 times smaller than the present-day value. At lower kinetic energies, Galactic cosmic ray modulation would have been even more severe. More generally, we find that the differential intensity of low-energy Galactic cosmic rays decreases at younger ages and is well described by a broken power law in solar rotation rate. We provide an analytic formula of our Galactic cosmic ray spectra at the Earth’s orbit for different ages. Our model is also applicable to other solar-type stars with exoplanets orbiting at different radii. Specifically, we use our Galactic cosmic ray spectrum at 20 au for t=600 Myr to estimate the penetration of cosmic rays in the atmosphere of HR 2562b, a directly imaged exoplanet orbiting a young solar-type star. We find that the majority of particles <0.1 GeV are attenuated at pressures ≳10−5 bar and thus do not reach altitudes below ∼100 km. Observationally constraining the Galactic cosmic ray spectrum in the atmosphere of a warm Jupiter would in turn help constrain the flux of cosmic rays reaching young Earth-like exoplanets

A spectral survey of an ultra-hot Jupiter: Detection of metals in the transmission spectrum of KELT-9 b

Context: KELT-9 b exemplifies a newly emerging class of short-period gaseous exoplanets that tend to orbit hot, early type stars - termed ultra-hot Jupiters. The severe stellar irradiation heats their atmospheres to temperatures of $\sim 4,000$ K, similar to the photospheres of dwarf stars. Due to the absence of aerosols and complex molecular chemistry at such temperatures, these planets offer the potential of detailed chemical characterisation through transit and day-side spectroscopy. Studies of their chemical inventories may provide crucial constraints on their formation process and evolution history. Aims: To search the optical transmission spectrum of KELT-9 b for absorption lines by metals using the cross-correlation technique. Methods: We analyse 2 transits observed with the HARPS-N spectrograph. We use an isothermal equilibrium chemistry model to predict the transmission spectrum for each of the neutral and singly-ionized atoms with atomic numbers between 3 and 78. Of these, we identify the elements that are expected to have spectral lines in the visible wavelength range and use those as cross-correlation templates. Results: We detect absorption of Na I, Cr II, Sc II and Y II, and confirm previous detections of Mg I, Fe I, Fe II and Ti II. In addition, we find evidence of Ca I, Cr I, Co I, and Sr II that will require further observations to verify. The detected absorption lines are significantly deeper than model predictions, suggesting that material is transported to higher altitudes where the density is enhanced compared to a hydrostatic profile. There appears to be no significant blue-shift of the absorption spectrum due to a net day-to-night side wind. In particular, the strong Fe II feature is shifted by $0.18 \pm 0.27$ km~s$^{-1}$, consistent with zero. Using the orbital velocity of the planet we revise the steller and planetary masses and radii.Comment: Submitted to Astronomy and Astrophysics on January 18, 2019. Accepted on May 3, 2019. 26 pages, 11 figure

Chain-Extendable Crosslinked Hydrogels Using Branching RAFT Modification

YesFunctional crosslinked hydrogels were prepared from 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA). The acid monomer was incorporated both via copolymerization and chain extension of a branching, reversible addition–fragmentation chain-transfer agent incorporated into the crosslinked polymer gel. The hydrogels were intolerant to high levels of acidic copolymerization as the acrylic acid weakened the ethylene glycol dimethacrylate (EGDMA) crosslinked network. Hydrogels made from HEMA, EGDMA and a branching RAFT agent provide the network with loose-chain end functionality that can be retained for subsequent chain extension. Traditional methods of surface functionalization have the downside of potentially creating a high volume of homopolymerization in the solution. Branching RAFT comonomers act as versatile anchor sites by which additional polymerization chain extension reactions can be carried out. Acrylic acid grafted onto HEMA–EGDMA hydrogels showed higher mechanical strength than the equivalent statistical copolymer networks and was shown to have functionality as an electrostatic binder of cationic flocculants

The effectiveness and satisfaction of web-based physiotherapy in people with spinal cord injury: a pilot randomised controlled trial

Study Design: Pilot randomised controlled trial. Objectives: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy for people with Spinal Cord Injury (SCI). Setting: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK. Methods: Twenty-four participants were recruited and randomised to receive eight weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based upon participant’s abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist. Results: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant were more pronounced for the 6 minute walk test. Participants were positive about using web-based physiotherapy and stated they would be happy to use it again and would recommend it to others. Overall it was rated as either good or excellent. Conclusions: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention, rated the programme highly and beneficial for health and well-being at various states post injury. The results of this study warrant further work with a more homogenous sample

Linear stability in billiards with potential

A general formula for the linearized Poincar\'e map of a billiard with a potential is derived. The stability of periodic orbits is given by the trace of a product of matrices describing the piecewise free motion between reflections and the contributions from the reflections alone. For the case without potential this gives well known formulas. Four billiards with potentials for which the free motion is integrable are treated as examples: The linear gravitational potential, the constant magnetic field, the harmonic potential, and a billiard in a rotating frame of reference, imitating the restricted three body problem. The linear stability of periodic orbits with period one and two is analyzed with the help of stability diagrams, showing the essential parameter dependence of the residue of the periodic orbits for these examples.Comment: 22 pages, LaTex, 4 Figure

Science Requirements and Conceptual Design for a Polarized Medium Energy Electron-Ion Collider at Jefferson Lab

This report presents a brief summary of the science opportunities and program of a polarized medium energy electron-ion collider at Jefferson Lab and a comprehensive description of the conceptual design of such a collider based on the CEBAF electron accelerator facility.Comment: 160 pages, ~93 figures This work was supported by the U.S. Department of Energy, Office of Nuclear Physics, under Contract No. DE-AC05-06OR23177, DE-AC02-06CH11357, DE-AC05-060R23177, and DESC0005823. The U.S. Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce this manuscript for U.S. Government purpose

Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure : a systematic review and meta-analysis

Aim: Recurrent implantation failure (RIF) affects 10% of couples undergoing assisted conception, often due to poor endometrial receptivity. We conducted a systematic review and meta‐analysis to evaluate the effectiveness of Intra‐venous intralipid (IVI) in improving pregnancy rates in women with history of RIF using. Methods: We searched MEDLINE, EMBASE, and CENTRAL for any randomized trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta‐analyzed data using a random effect model. Results: We included five randomized trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, risk ratio [RR] 1.55, 95% confidence interval [CI] 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95% CI 1.42–2.35, I2 0%) post treatment compared to no intervention. Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. Conclusion: There is limited evidence to support the use of IVI at the time of embryo transfer in women with the history of RIF. More research is needed before adopting it in clinical practice

Early versus delayed urinary catheter removal after hysterectomy : a systematic review and meta-analysis

Objectives In bladder drainage, an essential part of post-hysterectomy care, the optimal timing for removing the urinary catheter is unclear. Our objective was to evaluate the risks and benefits of early (6 h) catheter removal post-hysterectomy. Study design A systematic review searching MEDLINE, EMBASE and Cochrane CENTRAL from inception till May 2019 for randomised trials of women undergoing hysterectomy. We reported on urinary retention, positive urine culture, urinary tract infection (UTI) (defined by symptoms and/or antibiotic use), post-operative pyrexia, time to ambulation, and length of hospital stay. We assessed risk of bias in included trials and used a random-effect model to generate risk ratios (RR) for dichotomous outcomes and weighted mean differences (WMD) for continuous outcomes, with 95 % confidence intervals (CI). Results Of 1020 potentially relevant citations, we included 10 randomised trials (1120 women). Four trials had low risk of bias for randomisation and allocation concealment while five had low risk for outcome assessment and selective reporting. Compared to delayed removal, women in the early catheter removal group had a higher risk of urinary retention and needing re-catheterisation (10 RCTs, RR 3.61, 95 %CI 1.21–9.21, I 2 = 56 %). There was some reduction in the risk of post-operative UTI (6 RCTs, RR 0.42, 95 %CI 0.18 to 0.96, I 2 = 0 %), but we did not find a significant difference in post-operative pyrexia (6 RCTs, RR 0.73, 95 %CI 0.43–1.24, I 2 = 18 %) or positive urine cultures (6 RCTs, RR of 0.56, 95 %CI 0.27–1.12, I 2 = 55 %). There was no significant difference in the average time to ambulation (3RCTs, WMD −4.6, 95 %CI −9.16 to −0.18, I 2 = 98 %) and length of hospital stay (3RCTs, WMD −1.05, 95 %CI −2.42 to 0.31, I 2 = 98 %). Our meta-regression on the provision of prophylactic antibiotics did not show a significant effect on the reported outcomes. Our analysis was limited by our inability to adjust for potential effect modifiers such as the surgical route. Conclusions Early removal of the urinary catheter <6 h post-hysterectomy seems to increase the risk of urinary retention and needing re-catheterisation, but may reduce post-operative UTI