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BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document.METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work.RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost.CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

There is a paucity of data in the literature describing quantitative exposure of the ventral craniocervical junction through the endonasal corridor in a safe manner mindful of locoregional anatomy.To quantify ventromedial exposure of O-C1 and C1-2 articular structures after turning an inverted U-shaped nasopharyngeal flap (IUNF) and to obtain measurements assessing the distance of flap margins to adjacent neurovascular structures.In 8 cadaveric specimens, an IUNF was fashioned using a superior incision below the level of the pharyngeal tubercule of the clivus and lateral incisions in the approximate region of Rosenmuller fossae bilaterally. Measurements with calipers and/or neuronavigation software included flap dimensions, exposure of O-C1 and C1-2 articular structures, inferior reach of IUNF, and proximity of the internal carotid artery (ICA) and hypoglossal nerve to IUNF margins.The IUNF facilitated exposure of an average of 9 mm of the medial surfaces of the right/left O-C1 joints without transgression of the carotid arteries or hypoglossal nerves. The C1-2 articulation could not be routinely accessed. The margins of the IUNF were not in close (5 mm) proximity to the ICA in any of the 8 specimens. In 6 of 8 specimens, the dimensions of the IUNF were in close (5 mm) horizontal or vertical proximity to the hypoglossal foramina.The IUNF provided safe and reliable access to the medial O-C1 articulation. Given the close proximity of the exocranial hypoglossal foramen, neuronavigation assistance and neuromonitoring with attention to the superolateral IUNF margin are recommended.

Key summary points Aim To assess the impact on the older population of policies to decrease the overall impact of the COVID-19 pandemic in Europe. Findings Ageism has occurred during the COVID-19 pandemic. Message Analysis of the effects of the COVID-19 pandemic on the older population will help us to develop fairer and more inclusive policies in the future., Purpose The United Nations (UN) has published a Policy Brief on the impact of the Coronavirus Disease 2019 (COVID-19) that identifies policies and responses to protect older adults. Our objective was to summarize actions, health policies and clinical guidelines adopted by six European countries (Belgium, France, Italy, Poland, Spain and United Kingdom) during the pandemic, and to assess the impact of national policies on reducing adverse effects of the COVID-19 pandemic in older populations. Methods Reports by geriatricians on the measures and actions undertaken by governmental institutions in each country between March and July 2020, as well as the role of primary care during the pandemic, covered three areas: (a) general health strategies related to the pandemic; (b) impact of COVID-19 on health inequity; and (c) initiatives and challenges for the COVID-19 pandemic and beyond. Results In the six countries, COVID-19 mortality in nursing homes ranged from 26 to 66%. Although all countries endorsed the World Health Organization general recommendations, the reports identified the lack of harmonized European guidelines and policies for nursing homes, with competencies transferred to national (or regional) governments. All countries restricted visits in nursing homes, but no specific action plans were provided. The role of primary care was limited by the centralization of the crisis in hospital settings. Conclusions The older population has been greatly affected by COVID-19 and by the policies initiated to control its spread. The right to health and dignity are transgenerational; chronological age should not be the sole criterion in policy decisions.

GIS Day is an annual, international celebration of geographic information systems (GIS) and geospatial technologies that provides organizations with an opportunity to help others learn about the real-world applications and positive societal impacts of geography and GIS, highlight services, and celebrate accomplishments. Many academic libraries participate in GIS Day programs, using this well-known event to engage with their campus and local communities. In this article, we build on earlier research conducted by Weimer, Olivares, and Bedenbaugh to reassess the landscape of Association of Research Libraries (ARL) member involvement in GIS Day programs and, in particular, how these events demonstrate the educational and collaborative aspects of geospatial information services in libraries. For our web content analysis, we specifically focus on gathering information about GIS Day programs in 2019 and 2020, allowing for an examination of how libraries participating in GIS Day responded to the operational challenges posed by the COVID-19 pandemic, as well as new opportunities that may have emerged during this period. Finally, we offer our own 2020 GIS Day program as a brief example highlighting how it led to our first cross-institutional collaboration and fostered new opportunities for promoting and partnering on digital scholarship projects at our institutions. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chapter 2 investigates the significance of the property market in medieval Cambridge. It considers how far the property market at this time anticipated the urban property markets of today. Detailed information on the Cambridge property market is provided in the Hundred Rolls. A unique feature of the Rolls, compared to other sources such as rentals, is that they record all the rents paid on a property and not just the rent paid to one particular lord, such as the king or local lay lord. The rolls show that many properties paid multiple rents. With full information on each of these rents it possible to analyse separately the total rent paid and the various components of this rent going to individual lords. Chapter 2 introduces the statistical methods required to address these issues and reports the results obtained by applying them.

Refereed/Peer-reviewed Medication-related harm can occur during transitions of care. Revised Home Medicines Review (HMR) and Residential Medication Management Review (RMMR) program rules were published in April 2020 which allowed provision for some hospital medical practitioners to refer at-risk patients for medication review. In turn, the Society of Hospital Pharmacists of Australia's (SHPA's) Transitions of Care and Primary Care Leadership Committee developed a framework to support hospitals facilitating Hospital-Initiated Medication Reviews (HIMRs) via three pathways: HMR, RMMR, and Hospital Outreach Medication Review. Following the compilation of draft barriers and enablers to implementation of the SHPA HIMR framework, refinement occurred after broad consultation with hospital- and primary care-based pharmacists with transitions of care experience. The finalised list of barriers and enablers can inform broadscale implementation of the SHPA HIMR framework to reduce medication-related harm when high-risk patients transition from hospital to primary care and aged care.

One of the most important manuscripts surviving from thirteenth-century England, the corpus of documents known as the Hundred Rolls for Cambridge have been incomplete until the recent discovery of an additional roll. This invaluable volume replaces the previous inaccurate transcription by the record commission of 1818 and provides new translations and additional appendices. Shedding new light on important facets of business activity in thirteenth-century Cambridge, this volume makes a significant contribution to our knowledge of the early phases of capitalism. This unique text will be of interest to anyone working in the fields of economic and business history, entrepreneurship, philanthropy and medieval studies. A research monograph based on recently discovered historical documents, Compassionate Capitalism: Business and Community in Medieval England, by Casson et al, is also now available from Bristol University Press.

This chapter considers what factors contributed to the survival and success of the leading families, and to the decline of others. It identifies the crucial role of entrepreneurs in founding and sustaining the fortunes of leading families. A key finding of the chapter is the distinction between old aristocratic wealth and new mercantile wealth. Some older families fell into debt and lost their property portfolios. Others redistributed income within the family or undertook strategic marriages, and thus obtained a new lease of life.

The chapter provides new translations of these previously unpublished documents.

This book examines the evolution of compassionate capitalism in medieval England, using a unique and comprehensive source of information, the Cambridge Hundred Rolls. It demonstrates how compassionate capitalism developed through the bequest of rental income on property to charitable and religious institutions, such as hospitals, abbeys and friaries. This rental income was generated by the dramatic growth of an urban property market, through which wealthy merchants invested the profits of trade in property development. Compassionate capitalism was a driving force in the medieval economy from the mid-1200s to the Black Death of 1348. The Cambridge Hundred Rolls record a comprehensive survey of the town in 1279, profiling property location, ownership and use, the gifting of rents and the transmission of property between generations. It identifies over 30 leading family dynasties and the factors behind their rise and decline. By synthesising this information it is possible to reconstruct the economic topography of the town and to compare the occupational structure of different parishes. This leads to a fundamental revaluation of the topography of medieval Cambridge and the role of property markets in urban development. It also reveals the influence of religious teaching on the management of economic assets by family dynasties.

Family dynasties were important players in the property market of medieval Cambridge, the Hundred Rolls reveal. Using a wide range of archival sources this chapter examines the inter family relationships and cross family connections of 23 families identified from the rolls, including the Bartons, Blancgernuns and Dunnings. Strategies by which families accumulated and extended their property portfolios are examined. Causes of family decline and family success are considered.

Chapter 3 analyses the economic topography of the town, building on the results presented in Chapter 2. It investigates how far occupations were specialised in different part of the town. It constructs profiles of all the Cambridge parishes, showing how many properties were located in each, how much rent those properties paid, to whom they paid it, who held the properties, and in some cases their occupation too. It is also possible to chart the spatial distribution of occupational names. Because of the missing roll, it is possible for the first time to provide a definitive account of all the parishes. This corrects a bias in previous topographical accounts, which have over-emphasised the north and west of the town at the expense of the south and east.

Purpose In Scotland, individuals referred for NHS psychological therapies are expected to commence “treatment” within 18 weeks of receipt of referral. With high demand, high non-attendance rates and limited capacity, this can be a challenging goal. The service discussed here was keen to develop a way of seeing individuals referred sooner and improving the efficiency of the assessment process. The purpose of this paper is to look at the impact of introducing assessment (“Signpost”) appointments on waiting times, attendance, and treatment planning. Design/methodology/approach Signpost appointments were offered to all existing, and any new referrals, to an adult psychological therapies team (PTT) in NHS Lanarkshire. Clinicians kept a record of the outcomes of these appointments over a six month period. Waiting times and attendance figures were compared before and after the introduction of the Signpost system. Findings Following the introduction of Signpost appointments, individuals were seen sooner for both assessment and therapy. Attendance at first appointments improved and Signpost appointments helped inform treatment planning. Although alternatives were discussed, the majority of clients were still offered individual therapy. Service user and staff satisfaction was high. Practical implications The results from this study led to assessment (“Signpost”) appointments being rolled out across other adult PTTs in NHS Lanarkshire. Originality/value There is little research looking at the impact of assessment/signpost appointments on adult mental health services in the UK. In the current climate of public service cuts, this study provides an innovative way of reducing waiting times and maintaining service user satisfaction, without requiring more resources.

Although bone marrow, liver, thymus (BLT)-humanized mice provide a robust model for HIV-1 infection and enable evaluation of cure strategies dependent on endogenous immune responses, most mice develop graft versus host disease (GVHD), limiting their utility for extended HIV cure studies. This study aimed to: evaluate the GVHD-resistant C57 black 6 (C57BL/6) recombination activating gene 2 (Rag2)γcCD47 triple knockout (TKO)-BLT mouse as a model to establish HIV-1 latency. Determine whether TKO-BLT mice could be maintained on antiretroviral therapy (ART) for extended periods of time. Assess the rapidity of viral rebound following therapy interruption.TKO-BLT mice were HIV-1 infected, treated with various ART regimens over extended periods of time and assayed for viral rebound following therapy interruption.Daily subcutaneous injection and oral ART-mediated suppression of HIV-1 infection was tested at various doses in TKO-BLT mice. Mice were monitored for suppression of viremia and cellular HIV-1 RNA and DNA prior to and following therapy interruption.Mice remained healthy for 45 weeks posthumanization and could be treated with ART for up to 18 weeks. Viremia was suppressed to less than 200 copies/ml in the majority of mice with significant reductions in cellular HIV-1 RNA and DNA. Treatment interruption resulted in rapid viral recrudescence.HIV-1 latency can be maintained in TKO-BLT mice over extended periods on ART and rapid viral rebound occurs following therapy removal. The additional 15-18 weeks of healthy longevity compared with other BLT models provides sufficient time to examine the decay kinetics of the latent reservoir as well as observe delays in recrudescence in HIV-1 cure studies.

Neuroinflammation is a prominent component of several neurodegenerative diseases, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, tauopathies, amyotrophic lateral sclerosis and prion diseases. In such conditions, the ability to decrease neuroinflammation by drug therapy may influence disease progression. Statins have been used to treat hyperlipidemia as well as reduce neuroinflammation and oxidative stress in various tissues. In previous studies, treatment of scrapie-infected mice with the type 1 statins, simvastatin or pravastatin, showed a small beneficial effect on survival time. In the current study, to increase the effectiveness of statin therapy, we treated infected mice with atorvastatin, a type 2 statin that has improved pharmacokinetics over many type 1 statins. Treatments with either simvastatin or pravastatin were tested for comparison. We evaluated scrapie-infected mice for protease-resistant PrP (PrPres) accumulation, gliosis, neuroinflammation and time until advanced clinical disease requiring euthanasia. All three statin treatments reduced total serum cholesterol ≥40 % in mice. However, gliosis and PrPres deposition were similar in statin-treated and untreated infected mice. Time to euthanasia due to advanced clinical signs was not changed in statin-treated mice relative to untreated mice, a finding at odds with previous reports. Expression of 84 inflammatory genes involved in neuroinflammation was also quantitated. Seven genes were reduced by pravastatin, and one gene was reduced by atorvastatin. In contrast, simvastatin therapy did not reduce any of the tested genes, but did slightly increase the expression of Ccl2 and Cxcl13. Our studies indicate that none of the three statins tested were effective in reducing scrapie-induced neuroinflammation or neuropathogenesis.

The United Nations (UN) has published a Policy Brief on the impact of the Coronavirus Disease 2019 (COVID-19) that identifies policies and responses to protect older adults. Our objective was to summarize actions, health policies and clinical guidelines adopted by six European countries (Belgium, France, Italy, Poland, Spain and United Kingdom) during the pandemic, and to assess the impact of national policies on reducing adverse effects of the COVID-19 pandemic in older populations.Reports by geriatricians on the measures and actions undertaken by governmental institutions in each country between March and July 2020, as well as the role of primary care during the pandemic, covered three areas: (a) general health strategies related to the pandemic; (b) impact of COVID-19 on health inequity; and (c) initiatives and challenges for the COVID-19 pandemic and beyond.In the six countries, COVID-19 mortality in nursing homes ranged from 26 to 66%. Although all countries endorsed the World Health Organization general recommendations, the reports identified the lack of harmonized European guidelines and policies for nursing homes, with competencies transferred to national (or regional) governments. All countries restricted visits in nursing homes, but no specific action plans were provided. The role of primary care was limited by the centralization of the crisis in hospital settings.The older population has been greatly affected by COVID-19 and by the policies initiated to control its spread. The right to health and dignity are transgenerational; chronological age should not be the sole criterion in policy decisions.

Although all 12 subtypes of human interferon alpha (IFN-α) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in the control of different viral infections. The IFN-α2 subtype is currently in HIV-1 clinical trials, but it has not consistently reduced viral loads in HIV-1 patients and is not the most effective subtype against HIV-1 in vitro . We now demonstrate in humanized mice that, when delivered at the same high clinical dose, the human IFN-α14 subtype has very potent anti-HIV-1 activity whereas IFN-α2 does not. In both postexposure prophylaxis and treatment of acute infections, IFN-α14, but not IFN-α2, significantly suppressed HIV-1 replication and proviral loads. Furthermore, HIV-1-induced immune hyperactivation, which is a prognosticator of disease progression, was reduced by IFN-α14 but not IFN-α2. Whereas ineffective IFN-α2 therapy was associated with CD8 + T cell activation, successful IFN-α14 therapy was associated with increased intrinsic and innate immunity, including significantly higher induction of tetherin and MX2, increased APOBEC3G signature mutations in HIV-1 proviral DNA, and higher frequencies of TRAIL + NK cells. These results identify IFN-α14 as a potent new therapeutic that operates via mechanisms distinct from those of antiretroviral drugs. The ability of IFN-α14 to reduce both viremia and proviral loads in vivo suggests that it has strong potential as a component of a cure strategy for HIV-1 infections. The broad implication of these results is that the antiviral efficacy of each individual IFN-α subtype should be evaluated against the specific virus being treated. IMPORTANCE The naturally occurring antiviral protein IFN-α2 is used to treat hepatitis viruses but has proven rather ineffective against HIV in comparison to triple therapy with the antiretroviral (ARV) drugs. Although ARVs suppress the replication of HIV, they fail to completely clear infections. Since IFN-α acts by different mechanism than ARVs and has been shown to reduce HIV proviral loads, clinical trials are under way to test whether IFN-α2 combined with ARVs might eradicate HIV-1 infections. IFN-α is actually a family of 12 distinct proteins, and each IFN-α subtype has different efficacies toward different viruses. Here, we use mice that contain a human immune system, so they can be infected with HIV. With this model, we demonstrate that while IFN-α2 is only weakly effective against HIV, IFN-α14 is extremely potent. This discovery identifies IFN-α14 as a more powerful IFN-α subtype for use in combination therapy trials aimed toward an HIV cure.

Microglial activation is a hallmark of the neuroimmunological response to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion disease. The CX3C chemokine axis consists of fractalkine (CX3CL1) and its receptor (CX3CR1); these are expressed by neurons and microglia respectively, and are known to modulate microglial activation. In prion-infected mice, both Cx3cr1 and Cx3cl1 are altered, suggesting a role in disease. To investigate the influence of CX3C axis signalling on prion disease, we infected Cx3cr1 knockout (Cx3cr1-KO) and control mice with scrapie strains 22L and RML. Deletion of Cx3cr1 had no effect on development of clinical signs or disease incubation period. In addition, comparison of brain tissue from Cx3cr1-KO and control mice revealed no significant differences in cytokine levels, spongiosis, deposition of disease-associated prion protein or microglial activation. Thus, microglial activation during prion infection did not require CX3C axis signalling.

Keele University School of Medicine opened in 2002, initially delivering the Manchester MB ChB curriculum, with the aim that from 2007 it would deliver a 'distinctive Keele curriculum' which would 'graduate excellent clinicians'. This curriculum would be spiral and integrated in design, and delivered by a 'hybrid' model of learning methods, from small group interactive (including problem-based learning) through to large group and more didactic methods. It would be student-centred and include a strong focus on community and primary care contexts, the latter reflecting the origins of the university which grew out of the Workers' Education Alliance after the Second World War as the University College of North Staffordshire, becoming the University of Keele in 1962. The university has always had strong links with the Potteries and North Staffordshire, communities with long-standing problems of poor health status and recruitment of the necessary health workforce. While there are strong local drivers for medical students learning in and with the community, this is in a broader context of primary care becoming an increasingly important resource for medical undergraduate education arising from policy, health service and andragogy. We were charged with the responsibility of developing the community element of the curriculum. This paper describes the systematic development of our general practice curriculum from 2007 to the present. We describe the decisions we made and general practice's current contribution to the curriculum. We will present our evaluation of the curriculum in a separate paper.

Contains fulltext : 170105.pdf (Publisher’s version ) (Closed access) OBJECTIVE: We aimed to observe how an Option Grid decision aid for clinical encounters might be used where an interpreter is present, and to assess the impact of its use on shared decision making. METHODS: Data were available from three clinical consultations between patient, clinician (a physiotherapist), and interpreter about knee osteoarthritis. Clinicians were trained in the use of an Option Grid decision aid and the tool was used. Consultations were audio-recorded, transcribed, and translated by independent translators into English. RESULTS: Analysis revealed the difficulties with introducing a written decision aid into an interpreted consultation. The extra discussion needed between the clinician and interpreter around the principles and purpose of shared decision making and instructions regarding the Option Grid decision aid proved challenging and difficult to manage. Discussion of treatment options while using an Option Grid decision aid was predominantly done between clinician and interpreter. The patient appeared to have little involvement in discussion of treatment options. CONCLUSION: Patients were not active participants within the discussion. Further work needs to be done on how shared decision making can be achieved within interpreted consultations. PRACTICE IMPLICATIONS: Option Grid decision aids are not being used as intended in interpreted consultations.