Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection

Effects of surfactants on the formation of microdroplets in the flow focusing microfluidic device

Droplet-based in vitro compartmentalization (IVC) platform is a powerful tool in protein analysis. Reliable formation of microdroplets is important for the development of the microfluidic chip. In this study, we will examine the effect of surfactants on the formation of microdroplets in the flow focusing microfluidic device which is needed for enzyme evolution. Surfactants of Span 80 and Tween 20 are used in the continuous and dispersed phases, respectively. The droplet formation was affected distinguishably with the presence of Span 80 and Tween 20. The size of droplets decreased as the concentration of Span 80 increased. And the decrease was more pronounced with the combination of Span 80 and Tween 20

The RCPCH care pathway for children at risk of anaphylaxis:an evidence and consensus based national approach to caring for children with life-threatening allergies

Numerous studies have identified shortcomings in the management of children at risk of severe acute allergic reactions (anaphylaxis). The Science and Research Department at the Royal College of Paediatrics and Child Health (RCPCH) was commissioned by the Department of Health to develop competence based national care pathways for children with allergies. Anaphylaxis is the first completed pathway.The anaphylaxis pathway was developed by a multidisciplinary working group, reviewed by a broad group of stakeholders and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee.Pathway development is described under five headings: evidence review, mapping, external review, core knowledge documents and key recommendations. The full pathway can be downloaded from www.rcpch.ac.uk/allergy/anaphylaxis. This document describes the entry points and the ideal pathway of care from self-care through to follow-up. The five key recommendations focus on: (1) prompt administration of adrenaline by intramuscular injection; (2) referral to specialists with competence in paediatric allergies; (3) risk analysis; (4) provision of a self-management plan; and (5) suggested creation of a national anaphylaxis death register.We present the first national care pathway for anaphylaxis, which is based on a critique of published evidence, expert consensus and multi-stakeholder input including patient representation via the Anaphylaxis Campaign. The Project Board urges health professionals to work together across networks to improve care for children at risk of anaphylaxis, in particular during the period after an acute reaction. Additionally, the Project Board strongly recommends the funding of a national anaphylaxis register

When the business of sharing treatment decisions is not the same as shared decision making: A discourse analysis of decision sharing in general practice

Although shared decision making (SDM) in general practice continues to be promoted as a highly desirable means of conducting consultations it is rarely observed in practice. The aim of this study is to identify the discursive features and conversational strategies particular to the negotiation and sharing of treatment decisions in order to understand why SDM is not yet embedded into routine practice. Consultations from Scottish general practices were examined using discourse analysis. Two themes were identified as key components for when the doctor and the patient were intent on sharing decisions: the generation of patient involvement using first-person pronouns, and successful and unsuccessful patient requesting practices. This article identifies a number of conversational activities found to be successful in supporting doctors’ agendas and reducing their responsibility for decisions made. Doctor’s use of ‘partnership talk’ was found to minimize resistance and worked to invite consensus rather than involvement. The information from this study provides new insight into the consultation process by identifying how treatment decisions are arrived at through highlighting the complexities involved. Notably, shared decision making does not happen with the ease implied by current models and appears to work to maintain a biomedical ‘GP as expert’ approach rather than one in which the patient is truly involved in partnership. We suggest that further research on the impact of conversational activities is likely to benefit our understanding of shared decision making and hence training in and the practice of SDM

BSACI guideline for the set-up of penicillin allergy de-labelling services by non-allergists working in a hospital setting

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and a committee of experts and key stakeholders have developed this guideline for the evaluation and testing of patients with an unsubstantiated label of penicillin allergy. The guideline is intended for UK clinicians who are not trained in allergy or immunology, but who wish to develop a penicillin allergy de-labelling service for their patients. It is intended to supplement the BSACI 2015 guideline “Management of allergy to penicillin and other beta-lactams” and therefore does not detail the epidemiology or aetiology of penicillin allergy, as this is covered extensively in the 2015 guideline (1). The guideline is intended for use only in patients with a label of penicillin allergy and does not apply to other beta-lactam allergies. The recommendations include a checklist to identify patients at low risk of allergy and a framework for the conduct of drug provocation testing by non-allergists. There are separate sections for adults and paediatrics within the guideline, in recognition of the common differences in reported allergy history and likelihood of true allergy