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Recent Aß-immunotherapy trials have yielded the first clear evidence that removing aggregated Aß from the brains of symptomatic patients can slow the progression of Alzheimer's disease. The clinical benefit achieved in these trials has been modest, however, highlighting the need for both a deeper understanding of disease mechanisms and the importance of intervening early in the pathogenic cascade. An immunoprevention strategy for Alzheimer's disease is required that will integrate the findings from clinical trials with mechanistic insights from preclinical disease models to select promising antibodies, optimize the timing of intervention, identify early biomarkers, and mitigate potential side effects.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/terapia , Péptidos beta-Amiloides , Anticuerpos/uso terapéutico , Inmunoterapia , AnimalesRESUMEN
PURPOSE: We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia. METHODS: We searched PubMed, Cochrane CENTRAL, and 5 trial registries, as well as the reference lists of identified studies. We included randomized controlled trials comparing a monoclonal antibody with placebo at a dose consistent with that used in phase 3 trials or for Food and Drug Administration approval. Studies had to report at least 1 clinically relevant benefit or harm. Data were extracted independently by at least 2 researchers for random effects meta-analysis. Changes in cognitive and functional scales were compared between groups, and each difference was assessed to determine if it met the minimal clinically important difference (MCID). RESULTS: We identified 19 publications with 23,202 total participants that evaluated 8 anti-amyloid antibodies. There were small improvements over placebo in the Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 to -14 score (standardized mean difference = -0.07; 95% CI, -0.10 to -0.04), Mini Mental State Examination score (0.32 points; 95% CI, 0.13 to 0.50), and Clinical Dementia Rating-Sum of Boxes scale score (mean difference =-0.18 points; 95% CI, -0.34 to -0.03), and the combined functional scores (standardized mean difference = 0.09; 95% CI, 0.05 to 0.13). None of the changes, including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. Harms included significantly increased risks of amyloid-related imaging abnormalities (ARIA)-edema (relative risk [RR] = 10.29; number needed to harm [NNH] = 9), ARIA-hemorrhage (RR = 1.74; NNH = 13), and symptomatic ARIA-edema (RR = 24.3; NNH = 86). CONCLUSIONS: Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.
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Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Estados Unidos , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Pruebas de Estado Mental y Demencia , EdemaRESUMEN
This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid ß (Aß) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.
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Enfermedad de Alzheimer , Angiopatía Amiloide Cerebral , Trastornos Cerebrovasculares , Humanos , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Líquido Extracelular , Angiopatía Amiloide Cerebral/terapia , Angiopatía Amiloide Cerebral/patología , Encéfalo/metabolismo , Trastornos Cerebrovasculares/complicacionesRESUMEN
INTRODUCTION: Amyloid precursor protein (APP) transgenic mice are models of Alzheimer's disease (AD) amyloidosis, not all of AD. Diffuse, compacted, and vascular deposits in APP mice mimic those found in AD cases. METHODS: Most interventional studies in APP mice start treatment early in the process of amyloid deposition, consistent with a prevention treatment regimen. Most clinical trials treat patients with established amyloid deposits in a therapeutic treatment regimen. RESULTS: The first treatment to reduce amyloid and cognitive impairment in mice was immunotherapy. The APP mouse models not only predicted efficacy, but presaged the vascular leakage called ARIA. The recent immunotherapy clinical trials that removed amyloid and slowed cognitive decline confirms the utility of these early APP models when used in therapeutic designs. DISCUSSION: New mouse models of AD pathologies will add to the research armamentarium, but the early models have accurately predicted responses to amyloid therapies in humans.
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Enfermedad de Alzheimer , Amiloidosis , Disfunción Cognitiva , Humanos , Ratones , Animales , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/tratamiento farmacológico , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Ratones Transgénicos , Amiloidosis/terapia , Amiloidosis/metabolismo , Modelos Animales de Enfermedad , Péptidos beta-Amiloides/metabolismo , Placa Amiloide/patologíaRESUMEN
The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.
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Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Estados Unidos , Humanos , Enfermedad de Alzheimer/terapia , Cubierta de Hielo , Proteínas Amiloidogénicas , RadioinmunoterapiaRESUMEN
Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.
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Asma , Trastornos Respiratorios , Rinitis Alérgica , Rinitis , Humanos , Asma/diagnóstico , Asma/terapia , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/terapia , Biomarcadores , Atención Dirigida al PacienteRESUMEN
Amyloid-related imaging abnormalities (ARIA) is a term introduced in 2010 to encompass a spectrum of MRI findings observed in patients receiving investigational anti-amyloid beta (Aß) immunotherapies for Alzheimer disease (AD). The entity can be broadly categorized into ARIA characterized by edema and effusion (ARIA-E) and ARIA characterized by microhemorrhages and superficial siderosis (ARIA-H). ARIA typically occurs early in the treatment course and has a higher incidence in patients who are apolipoprotein E ε4 allele carriers. ARIA-E has an additional dose dependence, with higher incidence in patients receiving higher doses of anti-Aß immuno-therapies. ARIA is often asymptomatic and self-resolving. The recognition of ARIA has implications for patient selection and monitoring for Aß immunotherapies, and its development can potentially lead to a pause or discontinuation of therapy. The FDA's first approval of an Aß-targeting monoclonal antibody for AD treatment in 2021 will lead to such therapy's expanded use beyond the clinical trial setting and to radiologists more commonly encountering ARIA in clinical practice. This review explores the theorized pathophysiologic mechanisms for ARIA, describes the MRI findings and grading schemes for ARIA-E and AREA-H, and summarizes relevant Aß immunotherapies. Through such knowledge, radiologists can optimally impact the management of patients receiving targeted AD therapies.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/epidemiología , Péptidos beta-Amiloides/uso terapéutico , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: To describe the current management of allergic rhinitis (AR) in Spain's specialized care according to the next-generation ARIA guidelines. METHODS: An ad hoc online survey was distributed to AR specialists to appraise their perceptions of pathology management, knowledge of next-generation ARIA guidelines (including four case clinics), and their views on the principal barriers and the actions to proper AR management. RESULTS: one hundred nine specialists (38.5% allergists and 61.5% otolaryngologists) completed the study survey. Most respondents (87.2%) had read all or part of the Next-Generation ARIA Guidelines, and 81.6% stated that they considered the patient's treatment choice preferences. However, only 20.2% of specialists answered according to the recommendations in at least three of the four case clinics. Most participants failed to fulfill the treatment duration according to the guidelines. They regarded the lack of multidisciplinary teams (21.7%) and the lack of patients' AR treatment adherence (30.6%) as the most critical healthcare system- and patient-related barriers to the correct management of AR, respectively. Promoting patients' education was considered the most crucial action to improve it. CONCLUSION: Despite specialists' awareness, there is a gap between the evidence-based guidelines' recommendations and their implementation in clinical practice.
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Otolaringología , Rinitis Alérgica , Humanos , Rinitis Alérgica/tratamiento farmacológico , Encuestas y Cuestionarios , OtorrinolaringólogosRESUMEN
The global COVID-19 pandemic has imposed restrictions on people's movement, work and access to places at multiple international, national and sub-national scales. We need a better understanding of how the varied restrictions have impacted wildlife monitoring as gaps in data continuity caused by these disruptions may limit future data use and analysis. To assess the effect of different levels of COVID-19 restrictions on both citizen science and traditional wildlife monitoring, we analyse observational records of a widespread and iconic monotreme, the Australian short-beaked echidna (Tachyglossus aculeatus), in three states of Australia. We compare citizen science to observations from biodiversity data repositories across the three states by analysing numbers of observations, coverage in protected areas, and geographic distribution using an index of remoteness and accessibility. We analyse the effect of restriction levels by comparing these data from each restriction level in 2020 with corresponding periods in 2018-2019. Our results indicate that stricter and longer restrictions reduced numbers of scientific observations while citizen science showed few effects, though there is much variation due to differences in restriction levels in each state. Geographic distribution and coverage of protected and non-protected areas were also reduced for scientific monitoring while citizen science observations were little affected. This study shows that citizen science can continue to record accurate and widely distributed species observational data, despite pandemic restrictions, and thus demonstrates the potential value of citizen science to other researchers who require reliable data during periods of disruption.
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Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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Asma , Trastornos Respiratorios , Rinitis Alérgica , HumanosRESUMEN
OBJECTIVE: To improve safety and efficiency of radiotherapy process by customizing a Varian ARIA oncology information system following the guidelines provided in AAPM TG-100 report. METHODS: First, failure mode and effects analysis (FMEA) and quality management program were implemented for radiotherapy process. We have customized the visual care path in the ARIA system and set up a series of templates for simulation, prescription, contouring, treatment planning, and multiple checklists. Average time of activities' completion and amount of planning errors were compared before and after the use of the customized ARIA to evaluate its impact on the efficiency and safety of radiotherapy. RESULTS: Completion time and on-time completion rate of the key activities in the care path are improved. The time of OAR/targets contouring decreases from (1.94±1.51) days to (1.64±1.07) days (pâ=â0.003), with the on-time completion rate increases from 77.4%to 83.3%(pâ=â0.048). Treatment planning time decreases from (0.81±0.65) days to (0.55±0.51) days (pâ<â0.001), with the on-time completion rate increases from 96.6%to 98.3%(pâ=â0.163). Waiting time of patients decreases from (4.50±1.83) days to (4.04±1.34) days (pâ<â0.001), with the on-time completion rate increases from 81.9%to 89.7%(pâ=â0.003). In addition, the average plan error rate decreases from 5.5%(2.9%for safety errors and 2.6%for non-normative errors) to 2.4%(1.6%for safety errors and 0.8%for non-normative errors) (pâ=â0.029). CONCLUSION: Our study demonstrates that the customized ARIA system has the potential to promote efficiency and safety in radiotherapy process management. It is beneficial to organize and accelerate the treatment process with more effective communications and fewer errors.
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Oncología por Radiación , Lista de Verificación , Humanos , Sistemas de Información , Planificación de la Radioterapia Asistida por Computador , Programas InformáticosRESUMEN
BACKGROUND: Recent surveys revealed that the health status of many people from Hong Kong is far from ideal. Although non-communicable diseases are largely preventable, few relevant health promotion and disease prevention programs are available. Thus, we assessed the health indicators of Chinese adults in Hong Kong to investigate the relationship between obesity, common chronic diseases, and health-promoting lifestyle profiles to provide inspirations for decision makers in formulating targeted disease prevention and health management programs. METHODS: This is a secondary analysis of a data set of 270 community-dwelling Hong Kong adults who were within the eligible age range between 18 and 80 years without eye diseases that affect retinal photographs. The study exposure variable, health-promoting lifestyle profiles, was measured using the Health-Promoting Lifestyle Profile II (HPLP-II) questionnaire. The primary outcome variable, obesity, was defined using body mass index and waist-hip ratio. The secondary study outcome, estimated chronic diseases, including of anemia, chronic kidney disease, and cardiovascular disease, were estimated using automatic retinal image analysis from the retinal images. Data were analyzed using tests of proportion, the independent sample t-tests, Welch's t-test, and binary logistic regression models. RESULTS: All HPLP-II subscales had positive responses (≥ 2.5). Significant differences were noted between men and women in the health responsibility and nutrition subscales (Health Responsibility: p = 0.059; Nutrition: p = 0.067). Regression models revealed that nutrition (adjusted odds ratio [AOR] = 0.41; p = 0.017), physical activity (AOR = 0.50; p = 0.015), interpersonal relations (AOR = 2.14; p = 0.016), and stress management (AOR = 2.07; p 0.038) were associated with obesity; while spiritual growth (AOR = 0.24; p = 0.077) and interpersonal relations (AOR = 5.06; p 0.069) were associated with estimated chronic kidney disease. CONCLUSIONS: Improving health behaviors may control or alleviate the prevalence of obesity and chronic kidney disease. These findings could arouse concern about lifestyle behaviors and promote self-assessment of health-promoting lifestyles to the general public. The study also provided new insights into the relationship between the HPLP-II and other common chronic diseases that warrant further study.
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Promoción de la Salud , Estilo de Vida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Estudios Transversales , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Adulto JovenRESUMEN
In this paper, we present the first optimized implementation of ARIA block cipher on low-end 8-bit Alf and Vegard's RISC processor (AVR) microcontrollers. To achieve high-speed implementation, primitive operations, including rotation operation, a substitute layer, and a diffusion layer, are carefully optimized for the target low-end embedded processor. The proposed ARIA implementation supports the electronic codebook (ECB) and the counter (CTR) modes of operation. In particular, the CTR mode of operation is further optimized with the pre-computed table of two add-round-key, one substitute layer, and one diffusion layer operations. Finally, the proposed ARIA-CTR implementations on 8-bit AVR microcontrollers achieved 187.1, 216.8, and 246.6 clock cycles per byte for 128-bit, 192-bit, and 256-bit security levels, respectively. Compared with previous reference implementations, the execution timing is improved by 69.8%, 69.6%, and 69.5% for 128-bit, 192-bit, and 256-bit security levels, respectively.
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BACKGROUND: Australia provides health care services for Indigenous peoples as part of its effort to enhance Indigenous peoples' wellbeing. However, biomedical frameworks shape Australia's health care system, often without reference to Indigenous wellbeing priorities. Under Indigenous leadership the Interplay research project explored wellbeing for Indigenous Australians in remote regions, through defining and quantifying Indigenous people's values and priorities. This article aimed to quantify relationships between health care access, mental and physical health, and wellbeing to guide services to enhance wellbeing for Indigenous Australians in remote regions. METHODS: Indigenous and non-Indigenous researchers worked with Indigenous people in remote Australia to create a framework of wellbeing priorities. Indigenous community priorities were community, culture and empowerment; these interplay with government priorities for Indigenous development of health, education and employment. The wellbeing framework was further explored in four Indigenous communities through a survey which measured aspects of the wellbeing priorities. Indigenous community researchers administered the survey in their home communities to 841 Indigenous people aged 15 to 34 years from June 2014. From the survey items, exploratory factor analysis was used to develop constructs for mental and physical health, barriers to health care access and wellbeing. Relationships between these constructs were quantified through structural equation modelling. RESULTS: Participants reported high levels of health and physical health (mean scores (3.17/4 [SD 0.96]; and 3.76/4 [SD 0.73]) and wellbeing 8.07/10 [SD 1.94]. Transport and costs comprised the construct for barriers to health care access (mean access score 0.89/1 [SD 0.28]). Structural equation modelling showed that mental health, but not physical health was associated with wellbeing (ß = 0.25, P < 0.001; ß = - 0.038, P = 0.3). Health care access had an indirect positive relationship with wellbeing through mental health (ß = 0.047, P = 0.007). Relationships differed significantly for participants in remote compared with those in very remote communities. CONCLUSIONS: Greater attention to mental health and recognition of the role of services outside the health care sector may have positive impacts on wellbeing for Indigenous people in remote/ very remote Australia. Aggregation of remote and very remote populations may obscure important differences between Indigenous communities.
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Salud Mental , Nativos de Hawái y Otras Islas del Pacífico/psicología , Satisfacción Personal , Adolescente , Adulto , Australia , Femenino , Accesibilidad a los Servicios de Salud , Servicios de Salud del Indígena , Humanos , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.
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Asma/complicaciones , Aplicaciones Móviles , Calidad de Vida , Rinitis Alérgica/complicaciones , Encuestas y Cuestionarios , Adulto , Estudios Transversales , Europa (Continente) , Femenino , Humanos , Masculino , Proyectos Piloto , Rendimiento LaboralRESUMEN
BACKGROUND: Immunotherapeutic treatments targeting amyloid-ß plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. RESULTS: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. CONCLUSION: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. KEY POINTS: ⢠Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer's patients. ⢠The value of ARIA-E detection, classification and monitoring using subtraction was assessed. ⢠Validation of an established ARIA-E rating scale, recommendations for improvement are reported. ⢠Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement.
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Enfermedad de Alzheimer/complicaciones , Amiloidosis/diagnóstico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Edema Encefálico/diagnóstico , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Amiloidosis/complicaciones , Amiloidosis/tratamiento farmacológico , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Masculino , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND AND OBJECTIVE: the global prevalence of allergic rhinitis (AR) is rising and yet there is scarce information concerning the diagnosis, management and treatment patterns of AR in Northern Cyprus (NC). This study aims to provide a unique perspective on AR management as well as assessing the effectiveness of the pharmacist-led educational intervention for improving care of AR patients. METHODS: across-sectional survey was carried out with community pharmacists (n = 70), patients (n = 138) and ear, nose and throat (ENT) specialists (n = 12) in NC. For a controlled interventional trial, trained pharmacists provided a brief education on management of AR and nasal spray technique for patients while other pharmacists provided the usual care. Quality of life (QoL) and other outcome measures on the perceived symptom severity of the two groups were compared after a 6-week period. RESULTS: only 33.3% of the ear, nose and throat (ENT) specialists and 15.7% of the community pharmacists are aware of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The majority of patients (63%) self-managed with over-the-counter medications. Nasal congestion (96.4%) is the most bothersome symptom and oral antihistamines are the most commonly purchased medications (51.4%), indicating a pattern of suboptimal management. The pharmacists-led educational intervention has resulted in statistically more significant improvement in regards to nasal congestion and QoL for the intervention group patients (p < 0.05). CONCLUSION: the current management of AR has not been in accordance with the ARIA guidelines in NC. An educational intervention of the pharmacists can enhance the symptom management and improve the QoL in patients with AR.
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Otorrinolaringólogos , Educación del Paciente como Asunto , Farmacéuticos , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/tratamiento farmacológico , Adulto , Asma/etiología , Estudios Transversales/estadística & datos numéricos , Chipre/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Prevalencia , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Rinitis Alérgica/complicaciones , Encuestas y Cuestionarios/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
Background and Aims: Diversity of the genus Sorbus has been affected by interspecific hybridizations. Pink-flowered hybrid species have been insufficiently studied so far. They comprise bigenomic hybrid species derived from crosses S. aria s.l. × S. chamaemespilus and trigenomic ones, where S. aucuparia was involved as well. The main objective of the present study was to reconstruct their hybrid origins as well as to assess genetic distinction among several morphologically recognized hybrid species. Methods: Samples from putative maternal species and eight pink-flowered and two white-flowered hybrid species were collected in the Western Carpathians and the Sudetes. In total, 370 specimens were analysed. Six chloroplast microsatellites were used to infer parentage, whereas nuclear amplified fragment length polymorphism (AFLP) markers were employed for the identification of clones and patterns of genetic variation. Ploidy levels were estimated by flow cytometry on a subset of 140 individuals. Key Results: Genetic data supported their hybrid origins proposed based on flower and leaf morphology, and chloroplast DNA (cpDNA) revealed recurrent origins ( S. caeruleomontana , S. haljamovae ), even from bidirectional hybridization events ( S. zuzanae ). All bigenomic and trigenomic hybrid species (except triploid S. zuzanae ) were found to be tetraploid. In addition to polyploidy, low genetic variation and the presence of clones within and among populations were observed, suggesting predominantly apomictic reproduction of the hybrid species. Most of the described hybrid species appeared also genetically distinct. Conclusions: The data suggest that multiple hybridization events in the Western Carpathian Sorbus have led to the formation of separate, partially reproductively isolated genetic lineages, which may or may not be discriminated morphologically. Even bidirectional hybridization can produce individuals classified to the same taxon based on phenotype. For some hybrid taxa, hybridization pathways were proposed based on their genetic proximity to parental species and differences in genome sizes.
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Evolución Biológica , Hibridación Genética , Sorbus/genética , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , ADN de Cloroplastos/genética , Variación Genética , Repeticiones de Microsatélite , Poliploidía , EslovaquiaRESUMEN
To develop a low-cost private cloud platform of radiotherapy software. First, a private cloud platform which was based on OpenStack and the virtual GPU hardware was builded. Then on the private cloud platform, all the Varian radiotherapy software modules were installed to the virtual machine, and the corresponding function configuration was completed. Finally the software on the cloud was able to be accessed by virtual desktop client. The function test results of the cloud workstation show that a cloud workstation is equivalent to an isolated physical workstation, and any clients on the LAN can use the cloud workstation smoothly. The cloud platform transplantation in this study is economical and practical. The project not only improves the utilization rates of radiotherapy software, but also makes it possible that the cloud computing technology can expand its applications to the field of radiation oncology.