930 research outputs found
Mediation in the Law Curriculum
Cited by Lord Neuberger in ‘Educating Future Mediators’ at the 4th Civil Mediation Council National Conference, May 201
Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism
Predicting the public health benefit of vaccinating cattle against Escherichia coli O157
Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle–human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human–animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases
Barriers and facilitators to mobile phone use for people with aphasia
Purpose: Mobile phone use increases social participation. People with the communication disorder of aphasia are disadvantaged in the use of information and communication technology such as mobile phones and are reported to be more socially isolated than their peers. The World Health Organization's International Classification of Functioning, Disability and Health provides a framework to address the impact of environmental factors on individual participation. The aim of this preliminary study was to identify the barriers and facilitators to mobile phone use for people with aphasia. Method: A qualitative descriptive study involving two phases was conducted: (1) semi-structured interviews with 6 individuals with aphasia who owned or expressed a desire to own a mobile phone; (2) structured observations of key scenarios identified in the interviews of 3 participants who were sampled from the interview study. Results: Results identified 18 barriers and 9 facilitators to mobile phone use. Key barriers and facilitators were identified in the areas of design and features, written support and training, and communicative partners. Conclusion: Mobile phone use can be problematic for people with aphasia. Intervention needs to address the barriers and utilise the facilitators to mobile phone use for this population. Further research is required to inform policy and intervention programs to ensure that people with aphasia have access to this technology
Compact CMOS camera demonstrator (C3D) for Ukube-1
The Open University, in collaboration with e2v technologies and XCAM Ltd, have been selected to fly an EO (Earth Observation) technology demonstrator and in-orbit radiation damage characterisation instrument on board the UK Space Agency's UKube-1 pilot Cubesat programme. Cubesat payloads offer a unique opportunity to rapidly build and fly space hardware for minimal cost, providing easy access to the space environment. Based around the e2v 1.3 MPixel 0.18 micron process eye-on-Si CMOS devices, the instrument consists of a radiation characterisation imager as well as a narrow field imager (NFI) and a wide field imager (WFI). The narrow and wide field imagers are expected to achieve resolutions of 25 m and 350 m respectively from a 650 km orbit, providing sufficient swathe width to view the southern UK with the WFI and London with the NFI. The radiation characterisation experiment has been designed to verify and reinforce ground based testing that has been conducted on the e2v eye-on-Si family of devices and includes TEC temperature control circuitry as well as RADFET in-orbit dosimetry. Of particular interest are SEU and SEL effects. The novel instrument design allows for a wide range of capabilities within highly constrained mass, power and space budgets providing a model for future use on similarly constrained missions, such as planetary rovers. Scheduled for launch in December 2011, this 1 year low cost programme should not only provide valuable data and outreach opportunities but also help to prove flight heritage for future missions
Impact of pyrazinamide resistance on multidrug-resistant tuberculosis in Karakalpakstan, Uzbekistan.
SETTING: The World Health Organization (WHO) recommends the inclusion of pyrazinamide (PZA) in treatment regimens for multidrug-resistant tuberculosis (MDR-TB) unless resistance has been confirmed. OBJECTIVE: To investigate the association between PZA susceptibility and MDR-TB treatment outcome among patients treated with a PZA-containing regimen and whether the duration of the intensive phase of the PZA-containing regimen affected treatment outcome. DESIGN: We conducted a retrospective cohort study including all eligible MDR-TB patients starting treatment in 2003-2013 in the TB programme in Karakalpakstan, Uzbekistan. PZA drug susceptibility testing (DST) using liquid culture was performed, and outcomes were classified according to the WHO 2013 definitions. RESULTS: Of 2446 MDR-TB patients included, 832 (34.0%) had an available baseline PZA DST result, 612 (73.6%) of whom were PZA-resistant. We found no association between treatment success and PZA susceptibility (adjusted odds ratio [aOR] 0.86, 95%CI 0.51-1.44, P = 0.6) in patients treated with PZA. Furthermore, among patients with no baseline PZA DST result, no evidence was seen of an association between treatment success and PZA treatment duration (aOR 0.86, 95%CI 0.49-1.51, P = 0.6). CONCLUSION: Treatment of MDR-TB with a standard PZA regimen does not appear to improve treatment outcomes, regardless of PZA susceptibility or duration of treatment
Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics
<b>Background</b><p></p>
The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.<p></p>
<b>Methodology/Principal findings</b><p></p>
Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.<p></p>
<b>Conclusions/significance</b><p></p>
Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi
Vitamin D and SARS-Co V-2 virus/COVID-19 disease
Summary for social mediaVitamin D is essential for good health, especially bone and muscle health. Many people have low blood levels of vitamin D, especially in winter or if confined indoors, because summer sunshine is the main source of vitamin D for most people. Government vitamin D intake recommendations for the general population are 400 IU (10 µg) per day for the UK7 and 600 IU (15 µg) per day for the USA (800 IU (20 µg) per day for >70 years) and the EU.9 Taking a daily supplement (400 IU /day (10 µg/day) in the UK) and eating foods that provide vitamin D is particularly important for those self-isolating with limited exposure to sunlight. Vitamin D intakes greater than the upper limit of 4000 IU (100 µg) per day may be harmful and should be avoided unless under personal medical/clinical advice by a qualified health professional
Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women
Background & aims: Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP).
Methods: Twenty-four older women (65 ± 1 y) received (N ¼ 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V infusion of 13C6-phenylalanine was used to determine MPS at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 x 8 unilateral leg extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling via immunoblotting.
Results: Plasma insulineamia and EAAemia were greater and more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP. Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0e2 h, with MPS significantly higher than basal in the LEAA_6 and WP groups only over 0e4 h. However, FED-EX increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p-p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P < 0.05).
Conclusions: In conclusion, LEAA_1.5, despite only providing 0.6 g of leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP. Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism
Hydrogen Epoch of Reionization Array (HERA)
The Hydrogen Epoch of Reionization Array (HERA) is a staged experiment to
measure 21 cm emission from the primordial intergalactic medium (IGM)
throughout cosmic reionization (), and to explore earlier epochs of our
Cosmic Dawn (). During these epochs, early stars and black holes
heated and ionized the IGM, introducing fluctuations in 21 cm emission. HERA is
designed to characterize the evolution of the 21 cm power spectrum to constrain
the timing and morphology of reionization, the properties of the first
galaxies, the evolution of large-scale structure, and the early sources of
heating. The full HERA instrument will be a 350-element interferometer in South
Africa consisting of 14-m parabolic dishes observing from 50 to 250 MHz.
Currently, 19 dishes have been deployed on site and the next 18 are under
construction. HERA has been designated as an SKA Precursor instrument.
In this paper, we summarize HERA's scientific context and provide forecasts
for its key science results. After reviewing the current state of the art in
foreground mitigation, we use the delay-spectrum technique to motivate
high-level performance requirements for the HERA instrument. Next, we present
the HERA instrument design, along with the subsystem specifications that ensure
that HERA meets its performance requirements. Finally, we summarize the
schedule and status of the project. We conclude by suggesting that, given the
realities of foreground contamination, current-generation 21 cm instruments are
approaching their sensitivity limits. HERA is designed to bring both the
sensitivity and the precision to deliver its primary science on the basis of
proven foreground filtering techniques, while developing new subtraction
techniques to unlock new capabilities. The result will be a major step toward
realizing the widely recognized scientific potential of 21 cm cosmology.Comment: 26 pages, 24 figures, 2 table
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