Changes of renin-angiotensin system-related aminopeptidases in early stage Alzheimer's disease

Activities of aminopeptidases A, B, and N (ApA, ApB & ApN) and insulin-regulated aminopeptidase (IRAP) have been seen to be decreased amongst patients with Alzheimer's disease (AD). All of these enzymes are involved with the brain renin-angiotensin system which is believed to be involved with learning and memory. This study aimed to explore the time course and the mechanisms underlying these changes. Serum samples were collected from 45 AD patients at the start of the study, and again 13 months later (n = 37). The control group was 22 healthy, older, adults. Enzyme activity was determined at two substrate concentrations to allow Michaelis-Menten analysis of the enzyme activity. The results indicated that there was decreased activity of ApA, ApB and ApN amongst AD patients but no difference in serum IRAP activity. There were no associations between enzyme activity and age, gender nor scores on psychomotor tests. Consideration of the data for the two time points for AD patients showed that the changes in ApB occurred at an early stage of the disease and persisted, whilst those of ApA and ApN only became apparent at later stages of the disease. Although differences in Michaelis-Menten parameters were not statistically significant, consideration of the values suggested that the decrease in ApB activity may be a result of changes in enzyme protein conformation, whilst that of ApN may be a consequence of decreased enzyme expression. Importantly, the different time courses of the effects and the differential changes in enzyme affinity and expression indicated that the observed changes with progression of AD were not a ‘class effect’ for serum aminopeptidases but were idiosyncratic for the individual enzymes

Family physicians’ roles in long-term care homes and other congregate residential care settings during the COVID-19 pandemic: a qualitative study

Context: The COVID-19 pandemic disproportionally affected long-term care (LTC) homes and other community-based congregate residential care settings. Although family physicians (FPs) play important roles in the care of residents in LTC homes, provincial pandemic plans make few references to their specific roles in LTC. Objective: To examine the experiences of FPs providing care in LTC homes and other congregate care settings in Canada during the first year of the COVID-19 pandemic (2020–2021). Methods: As part of a multiple case study, we conducted semi-structured qualitative interviews with FPs across four Canadian regions. Interviews were transcribed, and a thematic analysis approach was employed. Findings: Twenty-one of the 68 FPs interviewed discussed providing care in congregate residential settings, including LTC. We identified three major themes: 1) the roles of FPs in community-based congregate residential care settings during a pandemic, 2) modification of the delivery of routine care, and 3) special workforce considerations in pandemic response for community-based congregate residential care settings. Limitations: We interviewed FPs in four Canadian jurisdictions between October 2020 and June 2021; findings may not be generalisable to later pandemic stages or to other provinces. Our recruitment strategy did not specifically target FPs who worked in different types of congregate residential care facilities; further research is needed to examine these settings in greater depth. Implications: FPs have a unique understanding of the populations they serve and are well suited to plan and implement community-adaptive procedures. Future pandemic plans should implement LTC-related FP roles during the pre-pandemic stage of a pandemic response

Enhanced Thermal Object Imaging by Photon Addition or Subtraction

Long-baseline interferometry (LBI) is used to reconstruct the image of faint thermal objects. The image quality, for a given exposure time, is in general limited by a low signal-to-noise ratio (SNR). We show theoretically that a significant increase of the SNR, in a LBI, is possible by adding or subtracting photons to the thermal beam. At low photon counts, photon addition-subtraction technology strongly enhances the image quality. We have experimentally realized a nondeterministic physical protocol for photon subtraction. Our theoretical predictions are supported by experimental results.Comment: 4 pages, 5 figure

Molecular Phylogeny of Edge Hill Virus Supports its Position in the Yellow Fever Virus Group and Identifies a New Genetic Variant

Edge Hill virus (EHV) is a mosquito-borne flavivirus isolated throughout Australia during mosquito surveillance programs. While not posing an immediate threat to the human population, EHV is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (YFV) sub-group to be detected within Australia. Here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the YFV-group. Isolates were not clustered based on geographical origin or time of isolation, suggesting that minimal genetic evolution of EHV has occurred over geographic distance or time within the EHV cluster. However, two isolates showed significant differences in antigenic reactivity patterns, and had a much larger divergence from the EHV prototype (19% nucleotide and 6% amino acid divergence), indicating a distinct subtype or variant within the EHV subgroup

Family physicians\u27 responses to personal protective equipment shortages in four regions in Canada: a qualitative study.

BACKGROUND: Despite well-documented increased demands and shortages of personal protective equipment (PPE) during previous disease outbreaks, health systems in Canada were poorly prepared to meet the need for PPE during the COVID-19 pandemic. In the primary care sector, PPE shortages impacted the delivery of health services and contributed to increased workload, fear, and anxiety among primary care providers. This study examines family physicians\u27 (FPs) response to PPE shortages during the first year of the COVID-19 pandemic to inform future pandemic planning. METHODS: As part of a multiple case study, we conducted semi-structured qualitative interviews with FPs across four regions in Canada. During the interviews, FPs were asked to describe the pandemic-related roles they performed over different stages of the pandemic, facilitators and barriers they experienced in performing these roles, and potential roles they could have filled. Interviews were transcribed and a thematic analysis approach was employed to identify recurring themes. For the current study, we examined themes related to PPE. RESULTS: A total of 68 FPs were interviewed across the four regions. Four overarching themes were identified: 1) factors associated with good PPE access, 2) managing PPE shortages, 3) impact of PPE shortages on practice and providers, and 4) symbolism of PPE in primary care. There was a wide discrepancy in access to PPE both within and across regions, and integration with hospital or regional health authorities often resulted in better access than community-based practices. When PPE was limited, FPs described rationing and reusing these resources in an effort to conserve, which often resulted in anxiety and personal safety concerns. Many FPs expressed that PPE shortages had come to symbolize neglect and a lack of concern for the primary care sector in the pandemic response. CONCLUSIONS: During the COVID-19 pandemic response, hospital-centric plans and a lack of prioritization for primary care led to shortages of PPE for family physicians. This study highlights the need to consider primary care in PPE conservation and allocation strategies and to examine the influence of the underlying organization of primary care on PPE distribution during the pandemic

Development of a primary care pandemic plan informed by in-depth policy analysis and interviews with family physicians across Canada during COVID-19: A qualitative case study protocol

Introduction Given the recurrent risk of respiratory illness-based pandemics, and the important roles family physicians play during public health emergencies, the development of pandemic plans for primary care is imperative. Existing pandemic plans in Canada, however, do not adequately incorporate family physicians\u27 roles and perspectives. This policy and planning oversight has become increasingly evident with the emergence of the novel coronavirus disease, COVID-19, pandemic. This study is designed to inform the development of pandemic plans for primary care through evidence from four provinces in Canada: British Columbia, Newfoundland and Labrador, Nova Scotia, and Ontario. Methods and analysis We will employ a multiple-case study of regions in four provinces. Each case consists of a mixed methods design which comprises: (1) a chronology of family physician roles in the COVID-19 pandemic response; (2) a provincial policy analysis; and (3) qualitative interviews with family physicians. Relevant policy and guidance documents will be identified through targeted, snowball and general search strategies. Additionally, these policy documents will be analysed to identify gaps and/or emphases in existing policies and policy responses. Interviews will explore family physicians\u27 proposed, actual and potential roles during the pandemic, the facilitators and barriers they have encountered throughout and the influence of gender on their professional roles. Data will be thematically analysed using a content analysis framework, first at the regional level and then through cross-case analyses. Ethics and dissemination Approval for this study has been granted by the Research Ethics of British Columbia, the Health Research Ethics Board of Newfoundland and Labrador, the Nova Scotia Health Authority Research Ethics Board and the Western University Research Ethics Board. Findings will be disseminated via conferences and peer-reviewed publications. Evidence and lessons learnt will be used to develop tools for government ministries, public health units and family physicians for improved pandemic response plans for primary care

Family physician leadership during the COVID-19 pandemic: roles, functions and key supports.

PURPOSE: Strong leadership in primary care is necessary to coordinate an effective pandemic response; however, descriptions of leadership roles for family physicians are absent from previous pandemic plans. This study aims to describe the leadership roles and functions family physicians played during the COVID-19 pandemic in Canada and identify supports and barriers to formalizing these roles in future pandemic plans. DESIGN/METHODOLOGY/APPROACH: This study conducted semi-structured qualitative interviews with family physicians across four regions in Canada as part of a multiple case study. During the interviews, participants were asked about their roles during each pandemic stage and the facilitators and barriers they experienced. Interviews were transcribed and a thematic analysis approach was used to identify recurring themes. FINDINGS: Sixty-eight family physicians completed interviews. Three key functions of family physician leadership during the pandemic were identified: conveying knowledge, developing and adapting protocols for primary care practices and advocacy. Each function involved curating and synthesizing information, tailoring communications based on individual needs and building upon established relationships. PRACTICAL IMPLICATIONS: Findings demonstrate the need for future pandemic plans to incorporate formal family physician leadership appointments, as well as supports such as training, communication aides and compensation to allow family physicians to enact these key roles. ORIGINALITY/VALUE: The COVID-19 pandemic presents a unique opportunity to examine the leadership roles of family physicians, which have been largely overlooked in past pandemic plans. This study\u27s findings highlight the importance of these roles toward delivering an effective and coordinated pandemic response with uninterrupted and safe access to primary care

Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.</p

The acute effect of tryptophan depletion on serum neurotrophin levels (BDNF, FGF2, and S100B) in healthy subjects

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National Guidelines for Digital Modelling

These National Guidelines and Case Studies for Digital Modelling are the outcomes from one of a number of Building Information Modelling (BIM)-related projects undertaken by the CRC for Construction Innovation. Since the CRC opened its doors in 2001, the industry has seen a rapid increase in interest in BIM, and widening adoption. These guidelines and case studies are thus very timely, as the industry moves to model-based working and starts to share models in a new context called integrated practice. Governments, both federal and state, and in New Zealand are starting to outline the role they might take, so that in contrast to the adoption of 2D CAD in the early 90s, we ensure that a national, industry-wide benefit results from this new paradigm of working. Section 1 of the guidelines give us an overview of BIM: how it affects our current mode of working, what we need to do to move to fully collaborative model-based facility development. The role of open standards such as IFC is described as a mechanism to support new processes, and make the extensive design and construction information available to asset operators and managers. Digital collaboration modes, types of models, levels of detail, object properties and model management complete this section. It will be relevant for owners, managers and project leaders as well as direct users of BIM. Section 2 provides recommendations and guides for key areas of model creation and development, and the move to simulation and performance measurement. These are the more practical parts of the guidelines developed for design professionals, BIM managers, technical staff and ‘in the field’ workers. The guidelines are supported by six case studies including a summary of lessons learnt about implementing BIM in Australian building projects. A key aspect of these publications is the identification of a number of important industry actions: the need for BIM-compatible product information and a national context for classifying product data; the need for an industry agreement and setting process-for-process definition; and finally, the need to ensure a national standard for sharing data between all of the participants in the facility-development process