A rapid high throughput proteomic method based on profiling of proteolytic free peptides to assess post-delivery degradation of placental tissue

A rapid method to determine quality for placental proteomic studies is required due to varying lengths of time between delivery and sampling in routine protocols. We developed a rapid 10 min LC-MS based scanning method to profile free peptides liberated from natural proteolytic degradation. The assay was applied to placenta samples obtained following refrigeration for varying time periods post-delivery (12 h, +24 h, +48 h and +72 h). Analysis reveals time dependant overlapping profiles for groups <24 to +48 h with greatest variation in the +72 h group, indicating that significant proteolysis affects tissue integrity between 48 and 72 h.This work was supported by the Economic and Social Research Council (ESRC) [Grant numbers ES/J007501/1, ES/L002507/1, ES/L002353/1, ES/L012871/1, ES/N007549/1] and as part of the GOSomics initiative at the National Institute for Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London and the UCL Biological Mass Spectrometry Research Centr

Eccentricity-dependent temporal contrast tuning in human visual cortex measured with fMRI.

Cells in the peripheral retina tend to have higher contrast sensitivity and respond at higher flicker frequencies than those closer to the fovea. Although this predicts increased behavioural temporal contrast sensitivity in the peripheral visual field, this effect is rarely observed in psychophysical experiments. It is unknown how temporal contrast sensitivity is represented across eccentricity within cortical visual field maps and whether such sensitivities reflect the response properties of retinal cells or psychophysical sensitivities. Here, we used functional magnetic resonance imaging (fMRI) to measure contrast sensitivity profiles at four temporal frequencies in five retinotopically-defined visual areas. We also measured population receptive field (pRF) parameters (polar angle, eccentricity, and size) in the same areas. Overall contrast sensitivity, independent of pRF parameters, peaked at 10Hz in all visual areas. In V1, V2, V3, and V3a, peripherally-tuned voxels had higher contrast sensitivity at a high temporal frequency (20Hz), while hV4 more closely reflected behavioural sensitivity profiles. We conclude that our data reflect a cortical representation of the increased peripheral temporal contrast sensitivity that is already present in the retina and that this bias must be compensated later in the cortical visual pathway

Contrast Adaptation Contributes to Contrast-Invariance of Orientation Tuning of Primate V1 Cells

BACKGROUND: Studies in rodents and carnivores have shown that orientation tuning width of single neurons does not change when stimulus contrast is modified. However, in these studies, stimuli were presented for a relatively long duration (e. g., 4 seconds), making it possible that contrast adaptation contributed to contrast-invariance of orientation tuning. Our first purpose was to determine, in marmoset area V1, whether orientation tuning is still contrast-invariant with the stimulation duration is comparable to that of a visual fixation. METHODOLOGY/PRINCIPAL FINDINGS: We performed extracellular recordings and examined orientation tuning of single-units using static sine-wave gratings that were flashed for 200 msec. Sixteen orientations and three contrast levels, representing low, medium and high values in the range of effective contrasts for each neuron, were randomly intermixed. Contrast adaptation being a slow phenomenon, cells did not have enough time to adapt to each contrast individually. With this stimulation protocol, we found that the tuning width obtained at intermediate contrast was reduced to 89% (median), and that at low contrast to 76%, of that obtained at high contrast. Therefore, when probed with briefly flashed stimuli, orientation tuning is not contrast-invariant in marmoset V1. Our second purpose was to determine whether contrast adaptation contributes to contrast-invariance of orientation tuning. Stationary gratings were presented, as previously, for 200 msec with randomly varying orientations, but the contrast was kept constant within stimulation blocks lasting >20 sec, allowing for adaptation to the single contrast in use. In these conditions, tuning widths obtained at low contrast were still significantly less than at high contrast (median 85%). However, tuning widths obtained with medium and high contrast stimuli no longer differed significantly. CONCLUSIONS/SIGNIFICANCE: Orientation tuning does not appear to be contrast-invariant when briefly flashed stimuli vary in both contrast and orientation, but contrast adaptation partially restores contrast-invariance of orientation tuning

Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study

The drug-induced liver injury network (DILIN) is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study

Pharmacies as providers of expanded health services for people who inject drugs: a review of laws, policies, and barriers in six countries

Background: People who inject drugs (PWID) are underserved by health providers but pharmacies may be their most accessible care settings. Methods: Studies in the U.S., Russia, Vietnam, China, Canada and Mexico employed a three-level (macro-, meso-, and micro-) model to assess feasibility of expanded pharmacy services for PWID. Studies employed qualitative and quantitative interviews, review of legal and policy documents, and information on the knowledge, attitudes, and practices of key stakeholders. Results: Studies produced a mixed assessment of feasibility. Provision of information and referrals by pharmacies is permissible in all study sites and sale and safe disposal of needles/syringes by pharmacies is legal in almost all sites, although needle/syringe sales face challenges related to attitudes and practices of pharmacists, police, and other actors. Pharmacy provision of HIV testing, hepatitis vaccination, opioid substitution treatment, provision of naloxone for drug overdose, and abscess treatment, face more serious legal and policy barriers. Discussion: Challenges to expanded services for drug users in pharmacies exist at all three levels, especially the macro-level characterized by legal barriers and persistent stigmatization of PWID. Where deficiencies in laws, policies, and community attitudes block implementation, stakeholders should advocate for needed legal and policy changes and work to address community stigma and resistance. Laws and policies are only as good as their implementation, so attention is also needed to meso- and micro- levels. Policies, attitudes, and practices of police departments and pharmacy chains as well as knowledge, attitudes, and practices of individual PWID, individual pharmacies, and police officers should support rather than undermine positive laws and expanded services. Despite the challenges, pharmacies remain potentially important venues for delivering health services to PWID.Other UBCNon UBCReviewedFacult

100 key research questions for the post-2015 development agenda

The Sustainable Development Goals (SDGs) herald a new phase for international development. This article presents the results of a consultative exercise to collaboratively identify 100 research questions of critical importance for the post-2015 international development agenda. The final shortlist is grouped into nine thematic areas and was selected by 21 representatives of international and non-governmental organisations and consultancies, and 14 academics with diverse disciplinary expertise from an initial pool of 704 questions submitted by 110 organisations based in 34 countries. The shortlist includes questions addressing long-standing problems, new challenges and broader issues related to development policies, practices and institutions. Collectively, these questions are relevant for future development-related research priorities of governmental and non-governmental organisations worldwide and could act as focal points for transdisciplinary research collaborations

A Hundred Key Questions for the Post-2015 Development Agenda

Marcia Vera Espinoza - ORCID: 0000-0001-6238-7683 https://orcid.org/0000-0001-6238-7683Item not available in this repository.This project was financially supported by SIID, the University of Sheffield’s Research and Innovation Services (R&IS), and the Innovation, Impact and Knowledge Exchange (IIKE) programme.https://www.unrisd.org/en/library/publications/a-hundred-key-questions-for-the-post-2015-development-agendapubpu