The European Filmmaker in Exile in Britain 1933-1945

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Highly sensitive detection of small ruminant bovine spongiform encephalopathy within transmissible spongiform encephalopathy mixes by serial protein misfolding cyclic amplification

It is assumed that sheep and goats consumed the same bovine spongiform encephalopathy (BSE)-contaminated meat and bone meal that was fed to cattle and precipitated the BSE epidemic in the United Kingdom that peaked more than 20 years ago. De- spite intensive surveillance for cases of BSE within the small ruminant populations of the United Kingdom and European Union, no instances of BSE have been detected in sheep, and in only two instances has BSE been discovered in goats. If BSE is present within the small ruminant populations, it may be at subclinical levels, may manifest as scrapie, or may be masked by coinfection with scrapie. To determine whether BSE is potentially circulating at low levels within the European small ruminant populations, highly sensitive assays that can specifically detect BSE, even within the presence of scrapie prion protein, are required. Here, we present a novel assay based on the specific amplification of BSE PrPSc using the serial protein misfolding cyclic amplification as- say (sPMCA), which specifically amplified small amounts of ovine and caprine BSE agent which had been mixed into a range of scrapie-positive brain homogenates. We detected the BSE prion protein within a large excess of classical, atypical, and CH1641 scrapie isolates. In a blind trial, this sPMCA-based assay specifically amplified BSE PrPSc within brain mixes with 100% specific- ity and 97% sensitivity when BSE agent was diluted into scrapie-infected brain homogenates at 1% (vol/vol)

Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro

Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system Protein Misfolding Cyclic Amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases

Séance d’apprentissage interprofessionnel animée par un pharmacien pour les résidents en médecine familiale spécialisés dans les soins liés au VIH

Implication Statement We developed a pharmacist-led one-month teaching rotation for medical residents to learn HIV pharmacotherapy.  This interprofessional education (IPE) was deemed extremely valuable by postgraduate-year-3 residents who intended to have a future practice in HIV care.  The overarching concept of this rotation was for the medical trainee to “become-the-pharmacist”, learning to recognize, prevent, and manage drug-related issues in HIV patients.  Pharmacist-led IPE should be considered to support medical training in other highly specialized pharmacotherapeutic areas.Énoncé des implications de la recherche Nous avons mis au point une formation sur la pharmacothérapie du VIH, présentée par un pharmacien, pour les résidents en médecine de troisième année. Ces derniers ont trouvé cette expérience d’apprentissage interprofessionnel extrêmement précieuse pour leurs interventions futures dans le traitement du VIH. Le concept au cœur de cette rotation d’une durée d’un mois était de mettre les stagiaires en médecine dans la peau du pharmacien pour leur apprendre à reconnaître, à prévenir et à gérer les problèmes liés à la prise de médicaments chez les patients séropositifs. Nous recommandons la formule d’apprentissage interprofessionnel mené par un pharmacien pour appuyer la formation médicale dans les domaines hautement spécialisés de la pharmacothérapie

Improving protein secondary structure prediction using a simple k-mer model

Motivation: Some first order methods for protein sequence analysis inherently treat each position as independent. We develop a general framework for introducing longer range interactions. We then demonstrate the power of our approach by applying it to secondary structure prediction; under the independence assumption, sequences produced by existing methods can produce features that are not protein like, an extreme example being a helix of length 1. Our goal was to make the predictions from state of the art methods more realistic, without loss of performance by other measures

Persistence of scrapie infectivity within a farm environment after cleaning and decontamination

Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs are directly implicated in the transmission of disease. In this study the effectiveness of recommended scrapie farm decontamination regimes was evaluated by a sheep bioassay using buildings naturally contaminated with scrapie. Pens within a farm building were treated with either 20,000ppm free chorine solution for one hour, or were treated to same but were followed with painting and full re-galvanisation or replacement of metalwork within the pen. Scrapie susceptible lambs of the PRNP genotype VRQ/VRQ were reared within these pens and their scrapie status was monitored by RAMALT. All animals became infected over an 18-month period, even in the pen that had been subject to the most stringent decontamination process. This data suggests that recommended current guidelines for the decontamination of farm buildings following outbreaks of scrapie do little to reduce the titre of infectious scrapie material and that environmental re-contamination could also be an issue associated with these premises

Methods for differentiating prion types in food-producing animals

Prions are an enigma amongst infectious disease agents as they lack a genome yet confer specific pathologies thought to be dictated mainly, if not solely, by the conformation of the disease form of the prion protein (PrPSc). Prion diseases affect humans and animals, the latter including the food-producing ruminant species cattle, sheep, goats and deer. Importantly, it has been shown that the disease agent of bovine spongiform encephalopathy (BSE) is zoonotic, causing variant Creutzfeldt Jakob disease (vCJD) in humans. Current diagnostic tests can distinguish different prion types and in food- producing animals these focus on the differentiation of BSE from the non-zoonotic agents. Whilst BSE cases are now rare, atypical forms of both scrapie and BSE have been reported, as well as two types of chronic wasting disease (CWD) in cervids. Typing of animal prion isolates remains an important aspect of prion diagnosis and is now becoming more focused on identifying the range of prion types that are present in food-producing animals and also developing tests that can screen for emerging, novel prion diseases. Here, we review prion typing methodologies in light of current and emerging prion types in food-producing animals

The Role of Bio-energy with Carbon Capture and Storage in Meeting the Climate Mitigation Challenge: A Whole System Perspective

This paper explores the role and implications of bio-energy with carbon capture and storage (BECCS) for addressing the climate change mitigation challenge. Framed within the context of the latest emissions budgets, and their associated uncertainty, we present a summary of the contribution of BECCS within the Integrated Assessment Model (IAM) scenarios used by the climate change community. Within this discussion we seek to shed light on two important areas. Firstly, that BECCS is a central, but often hidden element of many of the modelling work that underpins climate policy from the global to the national scale. The second area we address are the assumptions for BECCS embedded within IAM models, and the wider system consequences of these implied levels of deployment. In light of these challenges, we question whether BECCS can deliver what is anticipated of it within existing climate change policy