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1.
BackgroundResearchers are working at unprecedented speed to develop a SARS-CoV-2 vaccine. We aimed to assess the value of a hypothetical vaccine and its potential public health impact when prioritization is required due to supply constraints.MethodsA Markov cohort model was used to estimate COVID-19 related direct medical costs and deaths in the United States (US), with and without implementation of a 60% efficacious vaccine. To prioritize the vaccine under constrained supply, the population was divided into tiers based on age; risk and age; and occupation and age; and outcomes were compared across one year under various supply assumptions. The incremental cost per quality-adjusted life-year (QALY) gained versus no vaccine was calculated for the entire adult population and for each tier in the three prioritization schemes.ResultsThe incremental cost per QALY gained for the US adult population was $8,200 versus no vaccination. For the tiers at highest risk of complications from COVID-19, such as those ages 65 years and older, vaccination was cost-saving compared to no vaccination. The cost per QALY gained increased to over $94,000 for those with a low risk of hospitalization and death following infection. Results were most sensitive to infection incidence, vaccine price, the cost of treating COVID-19, and vaccine efficacy. Under the most optimistic supply scenario, the hypothetical vaccine may prevent 31% of expected deaths. As supply becomes more constrained, only 23% of deaths may be prevented. In lower supply scenarios, prioritization becomes more important to maximize the number of deaths prevented.ConclusionsA COVID-19 vaccine is predicted to be good value for money (cost per QALY gained <$50,000). The speed at which an effective vaccine can be made available will determine how much morbidity and mortality may be prevented in the US.  相似文献   
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Abstract

Alcohol hangover syndrome (AHS) is a highly heterogenous state encompassing a range of physiological and psychological symptoms. The syndrome is experienced regularly among alcohol consumers and remains poorly understood. The present study sought to gain insight into whether certain emotions were tied to AHS and how these emotions were experienced. Twenty participants took part, 14 female and 6 male, aged 21 to 39 years. Inductive thematic analysis of semi structured interview data produced four themes; ‘The Tyranny of the Shoulds’, ‘Bias and the Persistence of Memory’, ‘Staring into the Void’, and ‘Emotive behavioral response’. The four themes demonstrate the complexity of emotional experiences associated with AHS and account for concurrent constructs including cognition, mood, and behavior. Guilt, shame, dread, anger, and regret were all commonly experienced, with rumination, negative interpretation bias, nostalgia, self-flagellation, isolation and camaraderie being essential in how these emotions were described by participants. The study adds greater understanding of the diversity of emotions that can be experienced during AHS, with important implications for the wellbeing of those who suffer most from the state. It is suggested that self-help techniques targeting cognitions could be explored to help alleviate aspects of the negative emotions experienced.  相似文献   
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N-formyl peptide receptors(FPRs)were first identified upon phagocytic leukocytes,but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family.FPRs are expressed within neuronal tissues and markedly in the central nervous system,where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease,as well as neurological cancers such as neuroblastoma.Whilst the homeostatic function of FPRs in the nervous system is currently undefined,a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings.Rapid developments in recent years have implicated FPRs in the process of neurogenesis and neuronal differentiation which,upon greater characterisation,could represent a novel pharmacological target for neuronal regeneration therapies that may be used in the treatment of brain/spinal cord injury,stroke and neurodegeneration.This review aims to summarize the recent progress made to determine the physiological role of FPRs in a neuronal setting,and to put forward a case for FPRs as a novel pharmacological target for conditions of the nervous system,and for their potential to open the door to novel neuronal regeneration therapies.  相似文献   
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Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
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The production of medical imaging is a continuing trend in healthcare institutions. Quality assurance for planned radiation exposure situations (e.g. X-ray, computer tomography) requires examination-specific set-ups according to several parameters, such as patient’s age and weight, body region and clinical indication. These data are normally stored in several formats and with different nomenclatures, which hinder the continuous and automatic monitoring of these indicators and the comparison between several institutions and equipment. This article proposes a framework that aggregates, normalizes and provides different views over collected indicators. The developed tool can be used to improve the quality of radiologic procedures and also for benchmarking and auditing purposes. Finally, a case study and several experimental results related to radiation exposure and productivity are presented and discussed.  相似文献   
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Background

Convention dictates that an axillary view be obtained when evaluating proximal humerus fractures (PHF). However, the axillary view is frequently omitted because of pain and technical considerations. Furthermore, its diagnostic utility is unclear in this setting.

Questions/Purposes

The purpose of this study was to (1) determine the rate of obtaining an adequate axillary X-ray and complete shoulder series at a level I trauma center, (2) understand the cost of ordering and attempting an axillary radiograph, and (3) determine if axillary radiographs influence the management of PHF.

Patients and Methods

PHF treated between 2009 and 2011 that were ordered for an AP, scapular Y, and axillary view was identified. The types of radiographs actually obtained were recorded. The cost of obtaining three views and a single view of the shoulder with X-ray was determined. Lastly, three surgeons reviewed 42 PHF, both with and without an axillary view (AV), and treatment recommendations were compared.

Results

30% of PHF in this series had an adequate axillary view, and 14% received a complete trauma series. No factors could be identified that were associated with successfully obtaining an axillary view. Reviewers demonstrated substantial intraobserver reliability (κ = 0.759–0.808) regarding treatment recommendations for PHF with and without the axillary view. The addition of the AV had minimal influence on treatment recommendations.

Conclusion

Considering that the axillary view for PHF is painful, labor-intensive, costly, and does not appear to provide additional diagnostic value, orthopedic surgeons can consider foregoing the use of the axillary view when evaluating and treating PHF, particularly if other advanced imaging is utilized.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9445-9) contains supplementary material, which is available to authorized users.  相似文献   
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Malignant liver tumors represent approximately 1% of malignancies in children. HA is a high‐grade tumor of endothelial cells that is even more rare in the pediatric population. HA has a limited response to chemotherapy, radiation and resection with universal tumor recurrence with LT and nearly 100% mortality by 18 months. This is the first reported successful case of hepatic angiosarcoma in a child who was treated by LT in combination with sirolimus. Sirolimus antagonizes the mTOR pathway, which regulates cell proliferation, differentiation, and migration, and is being studied as an anti‐neoplastic agent for solid tumors.  相似文献   
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