Demography Is Not Destiny, Revisited

Looks at the impending demographic challenges of the aging American population. Considers the impact of factors in addition to anticipated changes in the size and age distribution, particularly those related to the economy and public policies

Demography Is Not Destiny

Examines demographic and economic trends, and other challenges and opportunities associated with the aging American population. Highlights the interactions that occur among public programs, private institutions, and individuals. Discusses policy options

Knowledge-based systems in Japan

This report summarizes a study of the state-of-the-art in knowledge-based systems technology in Japan, organized by the Japanese Technology Evaluation Center (JTEC) under the sponsorship of the National Science Foundation and the Advanced Research Projects Agency. The panel visited 19 Japanese sites in March 1992. Based on these site visits plus other interactions with Japanese organizations, both before and after the site visits, the panel prepared a draft final report. JTEC sent the draft to the host organizations for their review. The final report was published in May 1993

Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review.

BACKGROUND: Deposition of amyloid-beta (Abeta) in vessel walls of the brain as cerebral amyloid angiopathy (CAA) could be a major factor in the pathogenesis of dementia. Here we investigate the relationship between dementia and the prevalence of CAA in older populations. We searched the literature for prospective population-based epidemiological clinicopathological studies, free of the biases of other sampling techniques, which were used as a comparison. METHODS: To identify population-based studies assessing CAA and dementia, a previous systematic review of population-based clinicopathological studies of ageing and dementia was employed. To identify selected-sample studies, PsychInfo (1806-April Week 3 2008), OVID MEDLINE (1950-April Week 2 2008) and Pubmed (searched 21 April 2008) databases were searched using the term "amyloid angiopathy". These databases were also employed to search for any population-based studies not included in the previous systematic review. Studies were included if they reported the prevalence of CAA relative to a dementia classification (clinical or neuropathological). RESULTS: Four population-based studies were identified. They showed that on average 55-59% of those with dementia displayed CAA (of any severity) compared to 28-38% of the non-demented. 37-43% of the demented displayed severe CAA in contrast to 7-24% of the non-demented. There was no overlap in the range of these averages and they were less variable and lower than those reported in 38 selected sample studies (demented v non-demented: 32-100 v 0-77% regardless of severity; 0-50 v 0-11% for severe only). CONCLUSION: CAA prevalence in populations is consistently higher in the demented as compared to the non-demented. This supports a significant role for CAA in the pathogenesis of dementia

Hepcidin Increases Cytokines in Alzheimer's Disease and Down's Syndrome Dementia: Implication of Impaired Iron Homeostasis in Neuroinflammation.

The liver-derived hormone hepcidin, a member of the defensin family of antimicrobial peptides, plays an important role in host defense and innate immunity due to its broad antibacterial and antiviral properties. Ferritin, an iron storage protein is often associated with iron deficiency, hypoferritinemia, hypoxia, and immune complications, which are all significant concerns for systemic infection in Alzheimer's disease (AD) and Down's syndrome (DS) dementia. Serum and post-mortem brain samples were collected from AD, DS and age-matched control subjects. Serum samples were analyzed with ELISA for ferritin, hepcidin and IL-6. Additionally, post-mortem brain sections were assessed by immunohistochemistry for iron-related and inflammatory proteins. A significant increase in serum hepcidin levels was found in DS, compared to controls and AD subjects (p < 0.0001). Hepcidin protein was visible in the epithelial cells of choroid plexus, meningeal macrophages and in the astrocytes close to the endothelium of blood vessels. Hepcidin co-localized with IL-6, indicating its anti-inflammatory properties. We found significant correlation between hypoferritinemia and elevated levels of serum hepcidin in AD and DS. Hepcidin can be transported via macrophages and the majority of the vesicular hepcidin enters the brain via a compromised blood brain barrier (BBB). Our findings provide further insight into the molecular implications of the altered iron metabolism in acute inflammation, and can aid towards the development of preventive strategies and novel treatments in the fight against neuroinflammation

Hepcidin Increases Cytokines in Alzheimer's Disease and Down's Syndrome Dementia: Implication of Impaired Iron Homeostasis in Neuroinflammation.

The liver-derived hormone hepcidin, a member of the defensin family of antimicrobial peptides, plays an important role in host defense and innate immunity due to its broad antibacterial and antiviral properties. Ferritin, an iron storage protein is often associated with iron deficiency, hypoferritinemia, hypoxia, and immune complications, which are all significant concerns for systemic infection in Alzheimer's disease (AD) and Down's syndrome (DS) dementia. Serum and post-mortem brain samples were collected from AD, DS and age-matched control subjects. Serum samples were analyzed with ELISA for ferritin, hepcidin and IL-6. Additionally, post-mortem brain sections were assessed by immunohistochemistry for iron-related and inflammatory proteins. A significant increase in serum hepcidin levels was found in DS, compared to controls and AD subjects (p < 0.0001). Hepcidin protein was visible in the epithelial cells of choroid plexus, meningeal macrophages and in the astrocytes close to the endothelium of blood vessels. Hepcidin co-localized with IL-6, indicating its anti-inflammatory properties. We found significant correlation between hypoferritinemia and elevated levels of serum hepcidin in AD and DS. Hepcidin can be transported via macrophages and the majority of the vesicular hepcidin enters the brain via a compromised blood brain barrier (BBB). Our findings provide further insight into the molecular implications of the altered iron metabolism in acute inflammation, and can aid towards the development of preventive strategies and novel treatments in the fight against neuroinflammation

Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study.

Background: Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB. Methods: We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)-infected and -uninfected TB patients and controls, and a prospective cohort study of HIV-1-infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation. Results: MMP activity differed between HIV-1-infected and -uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1-infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1-uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis-antigen driven. Mycobacterium tuberculosis-induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro. Conclusions: MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1-infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS

National approaches to the vaccination of recently arrived migrants in Europe : A comparative policy analysis across 32 European countries

Funding Information: However, current approaches to the vaccination of migrants have not been well documented to date, and it is acknowledged that there are additional challenges in ensuring equitable access to vaccines in diverse and mobile migrant populations [9,11]. The ongoing refugee crisis has facilitated renewed dialogue around approaches to the screening and vaccination of recently arrived migrants for infectious diseases. The World Health Organization (WHO), United Nations High Commissioner for Refugees, and the United Nations Children's Fund recommended in 2015 that migrants in the WHO European Region should be vaccinated soon after arrival in accordance with the immunisation schedule of the receiving country in which they intend to stay for more than a week [11], and the European Centre for Disease Prevention and Control (ECDC) is currently developing guidance on approaches to vaccine-preventable diseases in newly arrived migrants [12]. However, there has to date been no comprehensive examination of what policies or guidelines are currently implemented across Europe, or how they compare across countries. In order to facilitate the harmonisation of vaccination policies across Europe and identify best practice, a clear understanding of the different policies and of the key gaps or inconsistencies in such policies is needed [13,14]. We therefore did a comparative analysis of policies and guidelines in EU/EEA countries and Switzerland relating to the provision of vaccinations to recently arrived migrants to identify common approached.This research was funded by the European Society of Clinical Microbiology and Infectious Diseases through the ESCMID Study Group for Infections in Travellers and Migrants (ESGITM). LBN, SH, and JSF receive funding from the UK National Institute for Health Research Imperial Biomedical Research Centre, the Imperial College Healthcare Charity, and the Wellcome Trust (Grant number 209993/Z/17/Z). Funding Information: This research was funded by the European Society of Clinical Microbiology and Infectious Diseases through the ESCMID Study Group for Infections in Travellers and Migrants (ESGITM). LBN, SH, and JSF receive funding from the UK National Institute for Health Research Imperial Biomedical Research Centre , the Imperial College Healthcare Charity , and the Wellcome Trust (Grant number 209993/Z/17/Z ). Publisher Copyright: © 2018 The AuthorsBackground: Migrants may be underimmunised and at higher risk of vaccine-preventable diseases, yet there has been no comprehensive examination of what policies are currently implemented across Europe targeting child and adult migrants. We analysed vaccination policies for migrants in 32 EU/EEA countries and Switzerland. Methods: Using framework analysis, we did a comparative analysis of national policies and guidelines pertaining to vaccination in recently arrived migrants through a systematic guideline and literature review and by approaching national experts. Results: Six (18.8%) of 32 countries had comprehensive policies specific to the vaccination of migrants (two focused only on child migrants, four on both adults and children). Nineteen (59.4%) countries applied their national vaccination schedule for migrant vaccinations, predominantly focusing on children; and five (15.6%) countries had circulated additional migrant-specific resources to relevant health-care providers. In six (18.8%) countries, policies on migrant vaccination focused on outbreak-specific vaccines only. In ten (31.3%) countries, policies focused on priority vaccinations, with polio being the vaccine most commonly administered and heterogeneity noted in vaccines recommended to adults, adolescents, and children. Eighteen (56.3%) countries recommended that an individual should be considered as unvaccinated where vaccination records were missing, and vaccines re-administered. Nine (28.1%) countries reported that specific vaccinations were mandatory. Conclusion: There is considerable variation in policies across Europe regarding approaches to vaccination in adult and child migrants, and a lack of clarity on optimum ways forward, what vaccines to offer, with a need for robust research in this area. More emphasis must be placed on ensuring migrant-specific guidance is disseminated to front-line healthcare professionals to improve vaccine delivery and uptake in diverse migration populations across the region.publishersversionPeer reviewe

Risk Factors for Obesity and High Blood Pressure in Chinese American Children: Maternal Acculturation and Children’s Food Choices

The objective of this study is to explore risk factors associated with overweight and high blood pressure in Chinese American children. Students and their parents were recruited from Chinese language schools in the San Francisco Bay Area. Data were collected on 67 children and their mothers, and included children’s weight, height, waist and hip circumferences, blood pressure, level of physical activity, dietary intake, usual food choice, knowledge about nutrition and physical activity, and self-efficacy regarding diet and physical activity. Mothers completed questionnaires on demographic data and acculturation. About 46% of children had a body mass index exceeding the 85th percentile. Lower level of maternal acculturation is a risk factor for overweight and higher waist to hip ratio. Children’s unhealthy food choices were predictive of high body mass index and high systolic blood pressure, whereas older age and less physical activity in children were predictors of high diastolic blood pressure. Developing culturally sensitive and developmentally appropriate interventions to reduce overweight and high blood pressure is critical to reduce health disparities among minority children

Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics

BACKGROUND Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings