3rd Annual Conference of the Leverhulme Centre for Integrative Research on Agriculture and Health (LCIRAH), Developing methods in agriculture and health research, London, 13–14 June 2013

Non-PRIFPRI3; ISI; CRP4; B Promoting healthy food systemsPHND; A4NHCGIAR Research Program on Agriculture for Nutrition and Health (A4NH

Assessment of Tapentadol API Abuse Liability with the Researched Abuse, Diversion and Addiction-Related Surveillance System

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted

Abuse and Diversion of Buprenorphine Sublingual Tablets and Film

Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants\u27 Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ( unique recipients of a dispensed drug, URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned

Sustained Reduction of Diversion and Abuse after Introduction of an Abuse Deterrent Formulation of Extended Release Oxycodone

Background: The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin®) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumventthe abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability ofthe initial reduction in abuse. Methods: Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. Results: OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Discussion: Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

<p>Abstract</p> <p>Background</p> <p>Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.</p> <p>Methods</p> <p>Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.</p> <p>Results</p> <p>Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.</p> <p>Conclusions</p> <p>Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.</p

Lignocellulose degradation mechanisms across the Tree of Life.

Organisms use diverse mechanisms involving multiple complementary enzymes, particularly glycoside hydrolases (GHs), to deconstruct lignocellulose. Lytic polysaccharide monooxygenases (LPMOs) produced by bacteria and fungi facilitate deconstruction as does the Fenton chemistry of brown-rot fungi. Lignin depolymerisation is achieved by white-rot fungi and certain bacteria, using peroxidases and laccases. Meta-omics is now revealing the complexity of prokaryotic degradative activity in lignocellulose-rich environments. Protists from termite guts and some oomycetes produce multiple lignocellulolytic enzymes. Lignocellulose-consuming animals secrete some GHs, but most harbour a diverse enzyme-secreting gut microflora in a mutualism that is particularly complex in termites. Shipworms however, house GH-secreting and LPMO-secreting bacteria separate from the site of digestion and the isopod Limnoria relies on endogenous enzymes alone. The omics revolution is identifying many novel enzymes and paradigms for biomass deconstruction, but more emphasis on function is required, particularly for enzyme cocktails, in which LPMOs may play an important role.The work of the teams at York, Portsmouth and Cambridge on development of ideas expressed in this review was supported by grants from BBSRC (BB/H531543/1, BB/L001926/1, BB/1018492/1, BB/K020358/1). The workshop was supported by a US Partnering grant from BBSRC (BB/G016208/1) to Cragg and a BBSRC/FAPESP grant to Bruce (BB/1018492/1). Watts was supported by Marie Curie FP7-RG 276948. Goodell acknowledges support from USDA Hatch Project S-1041 VA-136288. Distel acknowledges support from NSF Award IOS1442759 and NIH Award Number U19 TW008163. Beckham thanks the US Department of Energy Bioenergy Technologies Office for funding. We appreciated the hospitality of the Linnean Society in allowing us to meet in inspirational surroundings under portraits of Linnaeus, Darwin and Wallace.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.cbpa.2015.10.01

Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets

Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza

Interprofessional Education and Collaborative Practice (IPECP) in Post-COVID Healthcare Education and Practice Transformation Era – Discussion Paper. Joint Publication by InterprofessionalResearch.Global, American Interprofessional Health Collaborative & Canadian Interprofessional Health Collaborative

In the past two years the world has experienced unprecedented devastation, disruption, and death due to the COVID-19 global Pandemic. At the same time, the Pandemic acts as a transformation catalyst that accelerated the implementation and adoption of long overdue changes in healthcare education and practice, including telehealth and virtual learning.Interprofessional collaboration during the pandemic was able to foster healthcare transformation in several ways at the policy and legislative level, such as the fast-tracking of internationally trained professions. The role and use of digital technologies in healthcare education and practice have been extended and solidified by the pandemic. Macro-level policies acknowledging the importance ofpopulation health are key for future interprofessional collaboration of stakeholders to address inequalities. Similarly, interprofessional collaboration is key to addressing the proliferation of misinformation. Interprofessional education and collaborative practice (IPECP) can be effectively utilized to combat misinformation by increasing health literacy amongst health professions and the communities they serve.Despite IPECP being an integral component of promoting patient safety, and holistic, quality care, silos continue to exist. Furthermore, implementation of the Quintuple Aim (better health, better care, better value, better work experience, and better health equity), particularly through the lens of equity, remains elusive. Going forward, the integration and sustainability of IPECP are crucial and the experience of IPECP within the context of the COVID-19 pandemic should be reflected on, researched, and evaluated to inform future global healthcare systems and the workforce to provide and achieve the Quintuple Aim; the goal ofall in healthcare.As we are emerging out of the Pandemic, we have a unique opportunity to leverage on the lessons learned from the pandemic in fostering the healthcare transformation through innovation and IPECP. To capitalize on this opportunity and in a collaborative effort, the InterprofessionalResearch.Global (IPR.Global), the American Interprofessional Health Collaborative (AIHC), and the CanadianInterprofessional Health Collaborative (CIHC) have developed this e-book as a Discussion Paper to explore and discuss (from a global perspective) the impact and application of healthcare education and practice transformation on IPECP as we emerge from the COVID Pandemic with the goal to identify best practicesto integrate and sustain IPECP. We call the interprofessional educators, practitioners, leaders, scholars, and policy makers to utilize ‘Forward Thinking and Adaptability’ and ‘Sustainability and Growth’ in their IPECP approaches and strategies, to achieve Quintuple Aim. As learned during the Pandemic, working together – across professions, institutions, nationally, and globally – is essential in emerging stronger and in transforming our healthcare education and practice

The Solar Particle Acceleration Radiation and Kinetics (SPARK) Mission Concept

© 2023by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Particle acceleration is a fundamental process arising in many astrophysical objects, including active galactic nuclei, black holes, neutron stars, gamma-ray bursts, accretion disks, solar and stellar coronae, and planetary magnetospheres. Its ubiquity means energetic particles permeate the Universe and influence the conditions for the emergence and continuation of life. In our solar system, the Sun is the most energetic particle accelerator, and its proximity makes it a unique laboratory in which to explore astrophysical particle acceleration. However, despite its importance, the physics underlying solar particle acceleration remain poorly understood. The SPARK mission will reveal new discoveries about particle acceleration through a uniquely powerful and complete combination of γ-ray, X-ray, and EUV imaging and spectroscopy at high spectral, spatial, and temporal resolutions. SPARK’s instruments will provide a step change in observational capability, enabling fundamental breakthroughs in our understanding of solar particle acceleration and the phenomena associated with it, such as the evolution of solar eruptive events. By providing essential diagnostics of the processes that drive the onset and evolution of solar flares and coronal mass ejections, SPARK will elucidate the underlying physics of space weather events that can damage satellites and power grids, disrupt telecommunications and GPS navigation, and endanger astronauts in space. The prediction of such events and the mitigation of their potential impacts are crucial in protecting our terrestrial and space-based infrastructure.Peer reviewe