West Nile premembrane-envelope genetic vaccine encoded as a chimera containing the transmembrane and cytoplasmic domains of a lysosome-associated membrane protein: increased cellular concentration of the transgene product, targeting to the MHC II compartment, and enhanced neutralizing antibody response

AbstractA genetic vaccine for West Nile virus (WN) has been synthesized with the WN premembrane-envelope (WN preM-E) gene sequences encoded as a chimera with the transmembrane and carboxyl terminal domains of the lysosome-associated membrane protein (LAMP). The LAMP sequences are used to direct the antigen protein to the major histocompatibility class II (MHC II) vesicular compartment of transfected professional antigen-presenting cells (APCs). Vaccine constructs encoding the native WN preM-E and WN preM-E/LAMP chimera were synthesized in pVAX1 and pITR plasmid backbones. Extracts of human fibroblast 293 and monkey kidney COS-7 cells transfected with the WN preM-E/LAMP chimera constructs contained much greater amounts of E than did the cells transfected with constructs encoding the native WN preM-E. This difference in the concentration of native E and the E/LAMP chimera in transfected cells is attributed to the secretion of native E. The amount of preM protein in cell extracts, in contrast to the E protein, and the levels of DNA and RNA transcripts, did not differ between WN preM-E- and WN preM-E/LAMP-transfected cells. Additionally, confocal and immunoelectron microscopic analyses of transfected B cells showed localization of the WN preM-E/LAMP chimera in vesicular compartments containing endogenous LAMP, MHC II, and H2-M, whereas native viral preM-E lacking the LAMP sequences was distributed within the cellular vesicular network with little LAMP or MHC II association. Mice immunized with a DNA construct expressing the WN preM-E/LAMP antigen induced significant antibody and long-term neutralization titers in contrast to the minimal and short-lived neutralization titer of mice vaccinated with a plasmid expressing the untargeted antigen. These results underscore the utility of LAMP targeting of the WN envelope to the MHC II compartments in the design of a genetic WN vaccine

Development of a Patient Reported Experience Measure (PREM) for use in the ambulance service

Background NHS health policy emphasises the crucial role of patient experience as a core component of high quality care, alongside effectiveness and safety. Patient Reported Experience Measures (PREMs) measure patients’ experiences with their healthcare. They are increasingly being seen as valuable for assessing patient outcomes and differences in quality between health care providers. Previous patient surveys to assess ambulance service care have not been implemented routinely or in a standardised way. This research forms part of a doctoral study to develop a PREM for use in UK ambulance services. Methods The study comprised three subsections: 1. A secondary analysis of interview data exploring patients’ experiences of their prehospital care. 2. Development of questionnaire items based on those themes emerging from the secondary analysis. 3. Semi-structured interviews with service users that explore their opinions of the questionnaire items and whether the PREM includes all aspects of the ambulance service experience that should be encompassed. Results The secondary data analysis revealed specific ‘processes of importance’ to service users accessing ambulance care i.e. ‘timeliness’ and parallel ‘experiential components of care’ i.e. ‘reassurance’ that either enhanced or reduced the perception that the ‘processes of care’ were undertaken to a high standard. The key themes formed the foundation for generating the 53 item questionnaire. The interview stage is on-going and the data obtained are being used to amend the questionnaire items. Conclusions The construction of the PREM has incorporated the views of patients that the measure is ultimately designed for, and conforms to the concept of patient-centred care—the theoretical foundation of the research. Once completed, the PREM will enable ambulance trusts to measure differences in patient experiences, between and within organisations. This can result in positive changes to patient experience through the introduction of feedback, training and education to prehospital clinicians

STRUCTURE SHIFT IN INDONESIAN – ENGLISH TRANSLATION

Structure shift is one of the problems in translations. This problem is important to be dealt with because it is the most frequent category occurring at all rank in translation. Besides, in grammar structure shift can occur at all ranks. The discussion about structure shift only covers structure shift in phrase, clause, and sentence level. This research used the translation theory proposed by J.C. Catford (1965). He states that shift is departure from formal correspondence in the process of going form the SL to the TL. He also states that there are two kinds of shift in translating, namely level-shift and category-shift. Category shift means the change of formal structure of the SL, in process of translating into the TL. The data source is taken from four bilingual folklores. Data collecting used observation method and descriptive method was employed in analyzing the data. The findings show that in phrase level structure shift found only in noun and adjective phrase. The shifts in noun phrase are: H PostM PostM into PreM PreM H, H PostM into PreM H, and PreM H PostM Post M, into PreM PreM PreM H. In adjective phrase structure shift is found only one i.e. PreM H into H PostM. The structure shift in clause level is: SC into SVC, SV into SVA, and SV into SVO. In sentence level structure shift occur from simple sentence in SL into simple sentence in TL, simple sentence in SL into complex sentence in TL, complex sentence in SL into simple sentence in TL, and complec sentence in SL into complex sentence in TL

Measuring patients' experience with renal services in the UK: development and validation of the Kidney PREM

© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non Commercial License (https://creativecommons.org/licenses/by-nc/4.0/).Background Patient experience is a recognised aspect of quality of care for people with chronic kidney disease (CKD), but current patient-reported experience measures (PREMs) only focus on dialysis care. We developed and validated the Kidney PREM to assess patients’ experience with renal services in secondary care for any CKD stage or treatment (transplant, haemodialysis, peritoneal dialysis). Methods We developed the Kidney PREM in two phases, informed by a multidisciplinary expert group to ensure face validity. We organised three national data collections (2016 to 2018) to investigate item response profiles and to conduct exploratory and confirmatory analyses to assess internal consistency. We also explored content validity in cognitive interviews and evaluated test-retest reliability. Finally, we developed the Kidney PREM Short Form for more frequent measurement of patient experience to inform local service improvements. Results We analysed 32,959 responses across data collections, the 2018 collection covering all 71 UK renal centres. The Kidney PREM final version consisted of 38 items grouped in 13 themes, all pertaining to one underlying dimension reflecting the construct of ‘patient experience’ with high internal consistency (Cronbach’s α, .94). The Kidney PREM Short Form consisted of 15 items across the same 13 themes. Conclusions The Kidney PREM supports collection of reliable information on patient experience that people with CKD consider relevant, regardless of CKD stage or treatment modality. Kidney PREM data has the potential to guide local and national initiatives to improve patients’ experience with renal services in the UK and other countries.Peer reviewedFinal Published versio

Declarative Algorithms in Datalog with Extrema: Their Formal Semantics Simplified

Recent advances are making possible the use of aggregates in recursive queries thus enabling the declarative expression classic algorithms and their efficient and scalable implementation. These advances rely the notion of Pre-Mappability (PreM) of constraints that, along with the seminaive-fixpoint operational semantics, guarantees formal non-monotonic semantics for recursive programs with min and max constraints. In this extended abstract, we introduce basic templates to simplify and automate task of proving PreM

The initial psychometric evaluation of a new Emergency Department Patient-Reported Experience Measure (ED PREM)

Patient-reported experience measures (PREMs) are critical to evaluating the person-centeredness, safety, and quality of healthcare services internationally. The aim of this study was to describe the initial psychometric evaluation of a new Emergency Department (ED) PREM. Adult patients presenting to the ED of a tertiary hospital in southeast Queensland, Australia during January 2022 were recruited in-person. Participants selected their preferred ED PREM mode of administration from online, telephone, or postal, and had 14 days from recruitment to complete the survey. Item reduction, structural validity, discriminant validity, and internal consistency reliability were assessed. A sample of 349 (68.4%) was achieved. Item reduction analysis indicated ceiling effects for all ED PREM items (ranging between 34.4-79.7%). Exploratory factor analysis revealed a 4-factor solution comprising 26-items that explained 55% of model variance. Cronbach’s α ranged between 0.84-0.97 per factor, demonstrating internal consistency reliability. Known groups analysis demonstrated the ED PREMs’ ability to discriminate experiences based on gender, age, and ED length of stay. The ED PREM is a valid and reliable instrument for capturing patient experiences in the ED. The content of the ED PREM emphasizes person-centeredness and shared decision making, making it suitable for use in clinical practice evaluation and health service performance measurement. The factor structure of the ED PREM should be confirmed in future research, and item redundancy addressed. Experience Framework This article is associated with the Policy & Measurement lens of The Beryl Institute Experience Framework (https://theberylinstitute.org/experience-framework/). Access other PXJ articles related to this lens. Access other resources related to this lens