Mitigating the risk of Zika virus contamination of raw materials and cell lines in the manufacture of biologicals

Ensuring the virological safety of biologicals is challenging due to the risk of viral contamination of raw materials and cell banks, and exposure during in-process handling to known and/or emerging viral pathogens. Viruses may contaminate raw materials and biologicals intended for human or veterinary use and remain undetected until appropriate testing measures are employed. The outbreak and expansive spread of the mosquito-borne flavivirus Zika virus (ZIKV) poses challenges to screening human- and animal -derived products used in the manufacture of biologicals. Here, we report the results of an in vitro study where detector cell lines were challenged with African and Asian lineages of ZIKV. We demonstrate that this pathogen is robustly detectable by in vitro assay, thereby providing assurance of detection of ZIKV, and in turn underpinning the robustness of in vitro virology assays in safety testing of biologicals

Short communication: A practical farm-based trial to compare ewe nematode control strategies in peri-parturient ewes.

The focus of gastro-intestinal parasite control in the sheep industry is increasingly on finding a balance between maintaining productivity of the flock whilst minimising selection for anthelmintic resistance to preserve anthelmintic efficacy for the future. Periparturient ewes represent the major source of gastro-intestinal parasites for growing lambs and are therefore a priority for parasite control. This study examines the impact on ewe faecal egg counts (FECs), lamb FECs, lamb daily live weight gains (DLWGs) and pasture larval counts of treating groups of ewes two weeks prior to lambing with either, a long-acting moxidectin treatment, short-acting doramectin or control. Six groups of twenty ewes were allocated to individual paddocks, two groups allocated to each treatment, and weekly faecal sampling was performed throughout from the ewes and from six weeks after the start of lambing in the lambs. Treatment group was found to have a significant effect on both ewe FEC (p<0.001) and lamb FEC (p = 0.001) with the group receiving the long-acting anthelmintic having the lowest ewe and lamb FECs. There was no significant effect on the DLWGs of the lambs. Pasture larval counts at the end of the study period were lowest in the long-acting wormer treatment group. The use of long-acting moxidectin may be helpful as part of a parasite control programme by reducing the worm burdens of ewes and their lambs, decreasing the number of anthelmintic treatments required in that year and by reducing pasture contamination for those sheep which will graze the pasture in the next year. However, like all anthelmintics, its use should be judicious to avoid selection for resistance

Do High Frequency Ultrasound Images Support Clinical Skin Assessment?

High frequency ultrasound imaging has been reported as a potential method of identifying the suspected tissue damage in patients “at risk” of pressure ulceration. The aim of this study was to explore whether ultrasound images supported the clinical skin assessment in an inpatient population through identification of subcutaneous tissue damage. Skin on the heels and/or sacral coccygeal area of fifty vascular surgery inpatients was assessed clinically by tissue viability nurses and with ultrasound pre operatively and at least every other day until discharge. Images were compared to routine clinical skin assessment outcomes. Qualitative classification of ultrasound images did not match outcomes yielded through the clinical skin assessment. Images corresponding to 16 participants were classified as subgroup 3 damage at the heels (equivalent to grade 2 pressure ulceration); clinical skin assessment rated no heels as greater than grade 1a (blanching erythema). Conversely, all images captured of the sacral coccygeal area were classified as normal; the clinical skin assessment rated two participants as grade 1b (non-blanching erythema). Ultrasound imaging is a potentially useful adjunct to the clinical skin assessment in providing information about the underlying tissue. However, further longitudinal clinical assessment is required to characterise images against actual and “staged” pressure ulceration

Utilizing "Omic" technologies to identify and prioritize novel sources of resistance to the oomycete pathogen <i>Phytophthora infestans</i> in potato germplasm collections

The biggest threat to potato production world-wide is late blight, caused by the oomycete pathogen Phytophthora infestans. A screen of 126 wild diploid Solanum accessions from the Commonwealth Potato Collection (CPC) with P. infestans isolates belonging to the genotype 13-A2 identified resistances in the species S. bulbocastanum, S. capsicibaccatum, S. microdontum, S. mochiquense, S. okadae, S. pinnatisectum, S. polyadenium, S. tarijense and S. verrucosum. Effector-omics, allele mining and diagnostic RenSeq (dRenSeq) were utilized to investigate the nature of resistances in S. okadae accessions. dRenSeq in resistant S. okadae accessions 7129, 7625, 3762 and a bulk of 20 resistant progeny confirmed the presence of full-length Rpi-vnt1.1 under stringent mapping conditions and corroborated allele mining results in the accessions 7129 and 7625 as well as Avr-vnt1 recognition in transient expression assays. In contrast, susceptible S. okadae accession 3761 and a bulk of 20 susceptible progeny lacked sequence homology in the 5’ end compared to the functional Rpi-vnt1.1 gene. Further evaluation of S. okadae accessions with late blight isolates that have a broad spectrum of virulence demonstrated that, although S. okadae accessions 7129, 7625 and 7629 contain functional Rpi-vnt1.1, they also carry a novel resistance gene. We provide evidence that existing germplasm collection are important sources of novel resistances and that ‘omic’ technologies such as dRenSeq-based genomics and effector-omics are efficacious tools to rapidly explore the diversity within these collections

Disavowing 'the' prison

This chapter confronts the idea of ‘the’ prison, that is, prison as a fixed entity. However hard we, that is, prison scholars including ourselves, seek to deconstruct and critique specific aspects of confinement, there is a tendency to slip into a default position that envisions the prison as something given and pre-understood. When it comes to prison our imagination seems to clog up. It is the political solution to its own failure, and the preferred metaphor for its own representation

Preventing facial pressure injuries among health care staff working in diverse COVID‐19 care environments

The aim of this study was to determine the impact of a specially designed care bundle on the development of facial pressure injuries among frontline health care workers wearing personal protective equipment (PPE) during the COVID-19 pandemic. This was a mixed methods study. First, a pre-posttest observational design was employed to evaluate the impact of the pre-piloted intervention, a care bundle including skin cleansing and hydration, protective material use, facemask selection and skin inspection, developed in line with international best practice guidelines. Data were collected using survey methodology. Frontline COVID-19 staff working in acute, community and ambulance services were invited to participate. Then, judgemental and volunteer sampling was used to select participants to undertake semi-structured interviews to elicit feedback on their perceptions of the care bundle. The sample included 120 acute hospital staff, 60 Ambulance staff, 24 Community Hub staff and 20 COVID-19 testing centre staff. A survey response rate of 61% was realised (n = 135/224). Of the participants, 32% (n = 43) had a facial pressure ulcer (FPI) pre-intervention and 13% (n = 18) developed an FPI while using the care bundle. The odds ratio (OR) was 0.33 (95% CI: 0.18 to 0.61; P = .0004), indicating a 77% reduction in the odds of FPI development with use of the care bundle. Analysis of the qualitative data from 22 interviews identified three key themes, the context for the care bundle, the ease of use of the care bundle and the care bundle as a solution to FPI development. The care bundle reduced the incidence of FPI among the participants and was found to be easy to use. Implementation of skin protection for frontline staff continues to be important given the persistently high incidence of COVID-19 and the ongoing need to wear PPE for protracted durations

United Kingdom Frozen Shoulder Trial (UK FROST), multi-centre, randomised, 12 month, parallel group, superiority study to compare the clinical and cost-effectiveness of Early Structured Physiotherapy versus manipulation under anaesthesia versus arthroscopic capsular release for patients referred to secondary care with a primary frozen shoulder : study protocol for a randomised controlled trial

BACKGROUND: Frozen shoulder (also known as adhesive capsulitis) occurs when the capsule, or the soft tissue envelope around the ball and socket shoulder joint, becomes scarred and contracted, making the shoulder tight, painful and stiff. It affects around 1 in 12 men and 1 in 10 women of working age. Although this condition can settle with time (typically taking 1 to 3 years), for some people it causes severe symptoms and needs referral to hospital. Our aim is to evaluate the clinical and cost-effectiveness of two invasive and costly surgical interventions that are commonly used in secondary care in the National Health Service (NHS) compared with a non-surgical comparator of Early Structured Physiotherapy. METHODS: We will conduct a randomised controlled trial (RCT) of 500 adult patients with a clinical diagnosis of frozen shoulder, and who have radiographs that exclude other pathology. Early Structured Physiotherapy with an intra-articular steroid injection will be compared with manipulation under anaesthesia with a steroid injection or arthroscopic (keyhole) capsular release followed by manipulation. Both surgical interventions will be followed with a programme of post-procedural physiotherapy. These treatments will be undertaken in NHS hospitals across the United Kingdom. The primary outcome and endpoint will be the Oxford Shoulder Score (a patient self-reported assessment of shoulder function) at 12 months. This will also be measured at baseline, 3 and 6 months after randomisation; and on the day that treatment starts and 6 months later. Secondary outcomes include the Disabilities of Arm Shoulder and Hand (QuickDASH) score, the EQ-5D-5 L score, pain, extent of recovery and complications. We will explore the acceptability of the different treatments to patients and health care professionals using qualitative methods. DISCUSSION: The three treatments being compared are the most frequently used in secondary care in the NHS, but there is uncertainty about which one works best and at what cost. UK FROST is a rigorously designed and adequately powered study to inform clinical decisions for the treatment of this common condition in adults. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Register, ID: ISRCTN48804508 . Registered on 25 July 2014

Breast cancer screening in the era of density notification legislation: summary of 2014 Massachusetts experience and suggestion of an evidence-based management algorithm by multi-disciplinary expert panel

Purpose: Stemming from breast density notification legislation in Massachusetts effective 2015, we sought to develop a collaborative evidence-based approach to density notification that could be used by practitioners across the state. Our goal was to develop an evidence-based consensus management algorithm to help patients and health care providers follow best practices to implement a coordinated, evidence-based, cost-effective, sustainable practice and to standardize care in recommendations for supplemental screening. Methods: We formed the Massachusetts Breast Risk Education and Assessment Task Force (MA-BREAST) a multi-institutional, multi-disciplinary panel of expert radiologists, surgeons, primary care physicians, and oncologists to develop a collaborative approach to density notification legislation. Using evidence-based data from the Institute for Clinical and Economic Review (ICER), the Cochrane review, National Comprehensive Cancer Network (NCCN) guidelines, American Cancer Society (ACS) recommendations, and American College of Radiology (ACR) appropriateness criteria, the group collaboratively developed an evidence-based best-practices algorithm. Results: The expert consensus algorithm uses breast density as one element in the risk stratification to determine the need for supplemental screening. Women with dense breasts and otherwise low risk (20% lifetime) should consider supplemental screening MRI in addition to routine mammography regardless of breast density. Conclusion: We report the development of the multi-disciplinary collaborative approach to density notification. We propose a risk stratification algorithm to assess personal level of risk to determine the need for supplemental screening for an individual woman

Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

Purpose A handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device. Methods Healthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a “comfortable” position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10–20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions. Results Including one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p  0.5). Conclusions Moving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration